Title: NeuroTour 2023: A Federal Outlook of Neuroscience in Argentina

Chairs: On behalf of Federalization Commission of the SAN
Gabriela Salvador – INIBIBB-UNS-CONICET, salvador@criba.edu.ar
Fernando Gabriel Altamirano – Universidad Nacional de San Luis, fergabalt@gmail.com

Specific Goal of the NeuroTour Symposium

According to the information surveyed by the SAN in 2021, three districts in Argentina concentrate 90% of researchers in the area of Neuroscience: 61% are based in the city of Buenos Aires and 15% and 14% in the provinces of Córdoba and Buenos Aires, respectively. In this context, and within the framework of the recently created Federalization Commission of the SAN, a series of activities were carried out during 2022, including the organization of a pilot experience: the Federal

NeuroTour Symposium at the Annual Meeting.
In this first edition we gathered five researchers from outside the main research nodes representing the provinces of Tucumán, Chaco, Santa Fe, Entre Ríos, and Mendoza. Emphasis was made on inviting non-affiliated speakers and the inclusion of young investigators. We believe that fostering a federal community requires continual work over several years and even decades. For this reason, we present a second edition of the NeuroTour hoping to make this event a tradition within the SAN annual meeting.

As previously mentioned, the main goal of the Federal NeuroTour 2023 is to broaden the neuroscience network along our country. Consequently, the spirit of this symposium was to include several lines of investigation carried out in locations outside the main nodes of SAN. For this reason, in this symposium there is no specific research topic but rather a landscape of neuroscience done out of the most represented areas in SAN. Speakers that will participate in this symposium have their labs in Santa Fe, San Luis, Rio Negro and Tucumán.

Speakers

Maria Florencia Rossetti Instituto de Salud y Ambiente del Litoral, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral-CONICET- Santa Fe. Website:https://www.scopus.com/authid/detail.uri?authorId=56462267200
Title: “Offspring brain and placental programming in a rodent model of maternal cafeteria diet.”
Abstract: One of the objectives of her research project is to explore the importance of maternal nutritional environments during prenatal and early postnatal life on brain functions and to provide novel mechanisms through which such early experiences may lead to the onset of metabolic syndromes, neurodevelopmental disorders and other brain disorders later in life.

María Florencia Rossetti received her master’s degree in Biotechnology at the University of Litoral (UNL), Santa Fe. She obtained a Ph.D in Biological Sciences at the UNL. Currently, she works at the Instituto de Salud y Ambiente del Litoral, UNL-CONICET and Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, UNL in Santa Fe, Argentina.

Fernando Gabriel Altamirano Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis Web https://fergabalt2.wixsite.com/fernando-gabriel-alt
Title: “Chronobiological and epigenetic basis of cognitive functions in an aging model under caloric restriction”
Abstract: Caloric restriction (CR) positively influences aging processes affecting, among others, the cognitive capacities of the hippocampus.  Rhythmic variations in memory and associative learning processes throughout the day suggest the participation of the circadian clock in regulating these functions.  Despite growing evidence, the molecular basis of CR efficacy has not yet been fully elucidated, nor has the influence of this metabolic context on the temporal and circadian expression of factors related to cognition, antioxidant defense systems and epigenetic regulation remains unexplored.

Fernando Gabriel Altamirano received his master’s degree in Biological Sciences at the Universidad Nacional de San Luis, and he has obtained a Ph.D in Neuroscience (Universidad Nacional de Córdoba). Currently, he is a postdoctoral student at the Instituto de Investigación Médica Martín y Mercedes Ferreyra, working on the role of chromosome imbalance in energetic metabolism and cellular senescence.

María Soledad Espósito Departamento de Física Médica – Centro Atómico Bariloche, CNEA, San Carlos de Bariloche, Rio Negro Website https://www.scopus.com/authid/detail.uri?authorId=56019216600
Title: “Brainstem circuits for motor control in health and disease”
Abstract: Movement is a defining property of the animal kingdom. However, how the nervous system produces diverse and precise actions based on animals’ need continues to be the subject of deep research. This is because execution of diverse movements involves neuronal networks distributed throughout the nervous system. Brainstem motor centers are key components of these networks that have only recently begun to be unraveled establishing that specific brainstem subpopulations embedded into particular upstream and downstream circuits are dedicated to the execution of specific motor programs. The general goal of the lab is to contribute to the understanding of how precise brainstem circuits participate in the generation of particular motor behaviors in health and disease. We are currently focusing on two lines of research. On the one hand, we address the contribution of brainstem circuits to the acquisition of new motor skills. We postulate that motor learning takes place within a multi-level system in which distributed circuit elements, including brainstem circuits, contribute to the formation of a motor memory. Our results support our hypothesis demonstrating that midbrain glutamatergic neurons are necessary for the consolidation of a new motor skill. On the other hand, we are evaluating how particular brainstem circuit dysfunction underlies specific symptoms of Parkinson’s disease. To this end, we have developed a novel model of synucleinopathy which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.

Maria Soledad Esposito received her master’s degree in Biological Sciences at the University of Buenos Aires (UBA) and she obtained her Ph.D at the Leloir Institute Foundation focused on adult hippocampal neurogenesis. After graduating, she completed a postdoc at the Friedrich Miescher Institute for Biomedical Research in Switzerland. During her postdoc, she worked to characterize the connectivity between the brain and the spinal cord. Currently, she works at the Medical Physics Department at the Centro Atómico Bariloche, Rio Negro, Argentina.

Diego Ploper Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario, Tucumán.Web https://www.scopus.com/authid/detail.uri?authorId=36990454000
Title: “A Transgenic Cellular Model to Probe α-Synuclein Aggregation and Seeding for Parkinson’s Disease”
Abstract: The amyloid aggregation of α-synuclein (α-Syn) within dopaminergic neurons constitutes a pivotal hallmark of Parkinson’s disease (PD). The deleterious accumulation of this protein within dopaminergic neurons is believed to be a key contributor to the disease’s pathogenesis, with intercellular transfer of these aggregates posited as the primary mechanism for disease progression. Here we introduce an enhanced transgenic model designed to investigate α-Syn aggregation and seeding in cultured cells. By utilizing SHSY5Y cells stably overexpressing α-Syn-tagRFP, our study demonstrates that the application of exogenous recombinant human α-Syn preformed fibrils (α-Syn-PFF) elicits an elevation in the count of endogenous α-Syn-tagRFP puncta. Notably, these puncta exhibit positive signals for Thioflavin S (ThS), an amyloid-specific probe, as well as phospho-α-Syn (S129), a hallmark associated with toxic α-Syn species in PD. This observation suggests that exogenous fibrils can serve as seeds to catalyze aggregation of the endogenous protein. Additionally, exogenous α-Syn-PFF induced lysosomal biogenesis, revealing lysosomal stress. Importantly, these effects are confined to α-Syn amyloid fibrils, as exposure to amyloid fibrils originating from other proteins did not influence these parameters. Lastly, as a proof of concept, we illustrate the model’s utility in identifying novel compounds that inhibit α-Syn protein aggregation, phosphorylation, seeding, and uptake.

Diego Ploper received his master’s degree in chemistry at the University of Tucuman. He obtained his Ph.D in Biological Chemistry at the University of California, Los Angeles (2015) focused on Signaling Crosstalk between the Wnt, BMP and Endolysosomal Pathways in Development and Disease under the supervision of Prof. Edward De Robertis. Currently, he is working at Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario, Tucumán.

Organizers:
Antonia Marin Burgin, aburgin@ibioba-mpsp-conicet.gov.ar 
Noel Federman, nfederman@ibioba-mpsp-conicet.gov.ar
Sebastian Romano, sromano@ibioba-mpsp-conicet.gov.ar

Symposium summary
For most organisms, odorant cues guide behaviors critical for survival. However, olfactory processes are less understood than those of other sensory modalities. This symposium will cover recent work on how olfactory neuronal circuits of mammals transduce odorants into experience-dependent odor percepts. The symposium will have three talks addressing different aspects of odor processing highlighting new concepts in sensory processing related to the finding of multidimensional information in primary sensory areas.

Speakers

Kevin Franks, Duke University, USA
Title: Sequence decoding with millisecond precision in the olfactory cortex
Abstract: Neural sequences lasting tens to hundreds of milliseconds are thought to mediate essential cognitive processes, including navigation, memory encoding and retrieval, and sensory discrimination. However, the extent to which downstream cortical circuits can resolve the precise temporal structure of these sequences remains relatively unexplored. If so, the neural circuit operations that afford these circuits their exquisite temporal sensitivity are unclear.
In the olfactory system, odors activate different combinations of olfactory bulb (OB) glomeruli that respond with odor-specific onset latencies that tile the sniff cycle. Recent studies indicate that the precise timing of glomerular responses is critical for odor identification. However, the relative importance of glomerular identity versus glomerulus onset latencies in recruiting distinct ensembles of piriform cortex (PCx) neurons is unknown. As these factors are difficult to dissociate using odors, we used patterned optogenetic OB stimulation as fictive odor inputs while recording from large populations of mouse PCx neurons. Stimulating either non-overlapping glomeruli or stimulating the same glomeruli but shuffling their sequence order evoked equivalently distinct PCx responses. Remarkably, simply introducing small amounts of jitter in stimulus onset times (mean ISI ± st. dev: 5.2 ± 4.7 ms) when activating the same glomeruli in the same order evoked distinct PCx activity patterns.
We hypothesized that cortical inhibition would be critical for ensuring the temporal selectivity of PCx responses. However, surprisingly, dampening local inhibition actually improved response discriminability by slightly increasing the gain of PCx responses. Instead, we propose that the precise temporal selectivity we observe in PCx responses emerges through a delay-line architecture established by the combination of diffuse and distributed projections from OB to PCx and long-range recurrent connectivity between PCx neurons.
Our findings therefore provide insights into the general computational principles and mechanisms that underlie the encoding and decoding of precise neural sequences in cortical circuits.

Bio: Kevin Franks first learned about the plasticity of ocular dominance columns as an undergraduate studying Biomedical Science and Philosophy and has been fascinated about how experience shapes perception ever since. His Ph.D. work, with Terry Sejnowski at UCSD, involved modeling synaptic transmission and postsynaptic calcium dynamics. As a postdoc, first with Jeffry Isaacson at UCSD and then with Richard Axel and Steve Siegelbaum at Columbia, Kevin functionally and anatomically characterized piriform cortex circuitry. His lab is currently investigating different aspects of olfactory processing.

Cindy Poo, Allen Institute, USA
Title: Neural basis of odor-guided navigation
Abstract: Odors are a fundamental part of the sensory environment used by animals for ethological behaviors. In this talk, I will discuss our recent efforts towards understanding the neural basis of flexible behavior by investigating olfacto-hippocampal dynamics during navigation and foraging. Primary olfactory (piriform) cortex is thought to be dedicated to encoding odor identity. Using neural ensemble recordings in freely moving rats performing a novel odor-cued spatial choice task, we show that posterior piriform cortex neurons also carry a robust spatial map of the environment. Piriform spatial maps were stable across behavioral contexts independent of olfactory drive or reward availability, and the accuracy of spatial information carried by individual neurons depended on the strength of their functional coupling to the hippocampal theta rhythm. Ensembles of piriform neurons concurrently represented odor identity as well as spatial locations of animals, forming an “olfactory-place map”. Our results reveal a previously unknown function for piriform cortex in spatial cognition and suggest that it is well-suited to form odor-place associations and guide olfactory navigation. Finally, I will describe our current efforts in developing an odor patch foraging paradigm to study inter-regional dynamics during flexible decision making.

Bio: Cindy Poo received her undergraduate degree in neuroscience from Brown University. She completed her doctoral training in the laboratory of Dr. Jeffry Isaacson at the University of California, San Diego, where she used in vitro and in vivo patch-clamp recordings to understand synaptic mechanisms contributing to odor-evoked activity in olfactory cortex. Cindy was a postdoctoral researcher at the Champalimaud Research in Lisbon, Portugal, in the lab of Dr. Zachary Mainen. She was supported by postdoctoral fellowships from the Helen Hay Whitney Foundation and Human Frontiers Science Programme. She started recently he group at the Allen Institute. Her current research uses freely-moving and head-fixed rodent behavioral paradigms combined with contemporary electrophysiological recording, perturbation, and data analysis methods to further understand the olfactory system in the context of spatial navigation. Cindy’s long-term research goal is to understand the neural dynamics and mechanisms for olfactory perception, cognition, and behavior in distributed circuits across the brain.

Florin Albeanu, CSHL, USA.
Title: Sensorimotor prediction errors in the mouse olfactory cortex
Abstract: During behavior, sensation and action operate in closed-loop. Movements shape sensory input, and sensory inputs guide motor commands. Through experience, the brain may learn the reciprocal relationship between sensory inputs and movements to build internal models that accurately predict the sensory consequences of upcoming actions (sensorimotor predictions). This exchange of sensory inputs and egocentric expectations is at the core of active perception. In vertebrates, olfaction is intrinsically linked to motor action through sniffing and, just as for other sensory modalities, via head and body movements. However, due to technical challenges, most studies to date have probed olfactory processing during passive odor sampling. Even when studying odor-guided navigation, the effect of movements on olfactory representations has been rarely analyzed.

We hypothesized that, in closed-loop olfaction, mice predict the sensory consequences of their actions (next most probable odor input). Movement related predictions of expected odor input get compared with current odor input within olfactory cortex to represent olfacto-motor prediction errors. To test these hypotheses, we developed a closed-loop behavioral task (Smellocator) where head-fixed mice are trained to steer the left-right location of an odor source by controlling a light-weight lever with their forepaws. In this manner, 1) we link a precise motor action to well-defined sensory expectations (odor location) and 2) subsequently violate the learned expectations via an array of online sensorimotor feedback perturbations in expert animals.

Strikingly, expert mice readily counter brief sensorimotor perturbations, by making precise corrective movements that provide us a read-out of their individually learned sensorimotor predictions. Importantly, odor-driven responses in cortical (anterior olfactory nucleus and piriform) neurons are strongly re-shaped by olfacto-motor expectations. Transient and longer term (block-style) perturbations often trigger neural responses that are stronger than those evoked by any other task variable. Our results suggest that the olfactory cortex computes sensorimotor prediction errors by integrating sensory information with movement-related predictions, presumably relayed via top-down feedback. Using cell-type analysis and flexible activity manipulations, we are currently identifying the circuit elements that facilitate the comparison of olfactory inputs with olfacto-motor predictions.

Bio:
Florin Albeanu studied Biochemistry and Neuroscience at the University of Bucharest and at MIT. During his PhD at Harvard with Venki Murthy and Markus Meister, he investigated the logic of odor maps in the olfactory bulb. As a Fellow at Cold Spring Harbor Laboratory (CSHL), using patterned-illumination optogenetic methods, Florin analyzed input-output transformations in olfactory neural circuits. He is currently a Professor at CSHL and focuses on understanding the algorithms underlying sensorimotor transformations in the brain.

Antonia Marin Burgin, IBioBA-CONICET-Max Planck partner Institute, Argentina
Title: Learning embeds multidimensional encoding of experience in olfactory cortex
Abstract: Precise adaptation of behaviors relies on the capacity of animals to associate different types of information, such as multimodal sensory, internal state and motor signals, but it remains unclear where and how in the brain this integration occurs. We study whether individual neurons at the earliest stages of cortical odor processing can gather diverse aspects of behavior during learning. We developed a task in which mice explored a virtual corridor to learn that a particular odor is rewarded only when presented at a specific visual context, and performed piriform neuronal recordings in their first training session and when they became experts. Odor identity could be decoded from ensemble activity in both training stages. After learning, individual piriform neurons also carry information about a variety of olfactory, non-olfactory sensory, motor and cognitive task parameters. Expert animals show associative neuronal responses selective to individual visual context-odor combinations, and neurons that signal choice in anticipation of the animal’s response, revealing traces of cross-modal associations in a primary sensory cortex. Learning enhanced a multidimensional encoding scheme organized around odor-encoding neurons that integrate spatial context-dependent modulation and reward-related signals at a single-neuron level. Our findings suggest that learning entails computational mechanisms by which task-relevant information is embedded into olfactory processing in the piriform cortex, allowing sensory representations to be adjusted according to behavioral requirements.

Bio: Antonia Marin Burgin studied Biology at the University of Buenos Aires and obtained a PhD in Biological Sciences, University of Buenos Aires working on neuromodulatory circuits in the leech. She did a research internship at the Institute of Physiology, University of Wuerzburg, Germany where she worked on pain nociceptors during her PhD. Antonia was then a Postdoctoral Fellow at the University of California San Diego, USA where she worked with Bill Kristan in the development of sensory-motor circuit in the leech, and then with Massimo Scanziani working in interactions among excitatory and inhibitory circuits of the rodent hippocampus. She is currently a Principal Investigator at IBioBA-CONICET-Max Planck partner Institute in Buenos Aires. Her lab focuses in how experience shapes processing in both the hippocampus and the piriform cortex.

Chair:
Martin G. Frasch Department of Obstetrics and Gynecology, Center on Human Development and Disability, University of Washington, Seattle, WA, USA

Symposium summary

The brain as a predictive system that constantly defines itself versus the world around it, that is a concept that has been gaining traction in neuroscience, from cell to integrative scales of organization, expanding to immunology and drawing on the general notions of non-equilibrium thermodynamics and active inference. What is driving brain’s or immune system’s predictive computing in health and disease? There is some evidence that metabolic constraints play an important role. Across different scales of organization, from cell to the system level, there has been evidence for the role of cholinergic signaling and the vagus nerve, respectively, as the physiological substrates representing this concept. Here, we bring together experts from the respective fields of neuroscience and clinical medicine to share their insights in this fascinating field and generate fruitful conversations to fuel new ideas.

Speakers:

Harold Schulz (Confirmed) Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha.
https://www.unmc.edu/physiology/faculty/schultz.html
Title: “Physiological foundations of the vagal efferent and afferent circuitry.”
Abstract: It is now well accepted that alterations in sympathetic and vagal outflow far beyond the norm can both initiate disease and contribute to the progress and severity of many disorders. The complexity of the autonomic nervous system can be appreciated as one considers the central and peripheral interactions between neurons, glia, and other components of this system. It is important to appreciate this complexity when thinking about brain-body communication.

Francesco Cerritelli  (Confirmed, virtual) Department of Neuroscience, Imaging and Clinical Sciences | University “G. d’Annunzio” – Chieti. Italy
https://www.comecollaboration.org/wp-content/uploads/2015/04/1.cerritelli_europass_EN.pdf
Title: “The role of touch in the neurobiological development of the mother-newborn dyad”
Abstract: Touch is the most basic mammalian maternal behavior. As soon as an infant is born, mammalian mothers begin to engage in the species-typical repertoire of maternal behavior, and these postpartum behaviors consist primarily of close physical proximity and the provision of maternal touch. Being such a widespread mammalian behavior, early maternal touch must carry important implications for survival and adaptation and contribute to the growth and development of the young.

Anjalí Bhat Wellcome Centre for Human Neuroimaging, Queen Square Institute of Neurology, London, UK.
https://iris.ucl.ac.uk/iris/browse/profile?upi=ABHAT72
Title: “False inference in the brain and the immune system: Autoimmunity, allergies, hallucinations”
Abstract: A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? Answers may lie in the active inference paradigm. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people?

Martin Frasch  Department of Obstetrics and Gynecology, Center on Human Development and Disability, University of Washington, Seattle, WA, USA
https://depts.washington.edu/chdd/iddrc/res_aff/frasch.html
Title: “Multi-scale organization of cholinergic signaling in immunometabolism: is there evidence of immunoceptive inference?”
Abstract: There is strong evidence that immune and metabolic responses on cellular and systems scales are two sides of the same coin. The study of immunometabolism has yielded many insights into the joint nature of these physiological patterns. Cholinergic signaling and the vagus nerve appear in the center of these patterns, on the cellular scale – exemplified by the behavior of microglia; on the systems’ scale – exemplified by the responses to inflammation. 

Chairs:
Mariano Soiza-Reilly – PhD (msoizareilly@fbmc.fcen.uba.ar) – Instituto de Fisiología, Biología Molecular y Neurociencias (CONICET-UBA), C.A.B.A. Argentina.
Sebastian P Fernandez – PhD (fernandez@ipmc.cnrs.fr) – Institute Pharmacology Moléculaire Et Cellulaire (CNRS), Valbonne, France.

Symposium summary

Neuropsychiatric disorders represent a major global burden for health care systems and one of the most prevalent disabling conditions for individual’s life. The complexity of psychopathologies such as autism spectrum disorders, anxiety, depression and drug abuse, among others, have challenged our view about the structure and function of neural circuits, indicating that specific dysregulations in neurodevelopmental and/or adult molecular, cellular and connectivity events can have a direct impact on brain’s functional homeostasis and behavioral outputs. Recently developed techniques, genetic tools and analytical methods have contributed enormously to increase our knowledge in this regard. This symposium seeks to shed some light on recently uncovered maladaptive brain mechanisms underlying different aspects of neuropsychiatric disorders, and how these findings could help to develop novel prospective therapeutical treatments.

Speakers 

Jacques Barik, PhD – Institute Pharmacology Moléculaire Et Cellulaire (CNRS), Valbonne, France.
Title: “Nicotine disrupts Top-Down Habenular control over Cholinergic Signals to Gate Motivation”
Abstract: Smoking is a major contributor to disease burden worldwide, driven by dependence to nicotine, the primary reinforcing and addictive component of tobacco. Nicotine addiction is a chronic relapsing disorder associated with multiple psychiatric comorbidities, and few effective interventions currently exist to curb addiction to nicotine. The neurocircuitry underlying nicotine dependence is broad, complex and depends on the stages of the disease process. It is well-acknowledged that nicotine impacts the reward system with prominent alterations of the firing properties of VTA dopamine (DA) neurons consequently biasing the responses to natural and addictive rewards. Yet the underlying mechanisms responsible of VTA DA alterations remain elusive. Here, we exposed mice to chronic nicotine in their drinking water to mimic the prolonged and intermittent nicotine absorption of nicotine in humans. Combining viral tracers and optogenetic approaches, we aim to investigate the effects of long-term nicotine intake on inputs to the reward system, establishing a parallel between
circuit-based electrophysiological analyses and behavioral assessments in an operant conditioning task. We will present data showing that chronic nicotine consumption induces cellular alterations within inputs to the reward system that relate to changes in motivational state for natural rewards.
These changes may influence the incentive attribution process induced by drugs of abuse in the addiction process.

Natalia De Marco Garcia, PhD – Weill Cornell Medical College, NY, USA.
Title: “The Emergence of Network Activity Patterns-An Early Window to Autism Spectrum Disorder”
Abstract: During neonatal development, sensory cortices generate spontaneous activity patterns shaped byboth sensory experience and intrinsic influences. How these patterns contribute to the assembly of neuronal circuits is not clearly understood. Using in vivo calcium imaging in young mouse pups, we show that spatially segregated assemblies of interneuron and pyramidal cells are already evident at neonatal stages. In this talk, I will cover recent work from my lab indicating that GABAergic inputs shape cortical network patterns that balance the number of interneurons integrating into maturing cortical networks during a critical window of development. In addition, I will discuss how imaging approaches including longitudinal 2-photon and widefield calcium imaging can be used to study the
link between genetic predispositions for neurodevelopmental disorders and their impact on early network dynamics, and functional connectivity.

Francois Georges, PhD – Institut des Maladies Neurodégénératives (CNRS), Bordeaux, France.
Titlte: “Emotion in Action: Anatomical and Functional characterization of Amygdala-Striatal circuits”
Abstract: In humans and animals, changes in emotional states are known to modify posture, fine motor control, and/or coordination, inducing either beneficial or detrimental effects on motor performance. This suggests an overlap between neural circuits underlying emotions (limbic system) and motor control (basal ganglia). We thus performed an extensive review of the anatomical limbicto-basal ganglia direct connections and chose to focus on the amygdala to caudate-putamen (CPu) projections in mice. The CPu is the gate of entry of the basal ganglia and is involved in action selection and movement. The amygdala is a key limbic structure involved in emotional processing.
We hypothesize that amygdala-CPu neurons can trigger emotional modulation of movement. Using anatomical tracing tools, combined with in vivo and ex-vivo electrophysiology and fiber photometry, we show that the basolateral amygdala (BLA) complex is the main amygdala input to the CPu. These excitatory projections preferentially target medium-spiny neurons and parvalbumin interneurons. To define this neuronal sub-population, we mapped the inputs and outputs of the BLA-CPu neurons and determined the sources of their neuromodulators. Calcium imaging in vivo further confirms the functional connectivity of the main inputs to BLA-CPu neurons and shows that they respond to different sensory challenges.

Marisela Morales, PhD National Institutes of Drug Abuse-NIH, Baltimore, USA.
Title: “Ventral tegmental area neuronal diversity, connectivity, unanticipated types ofneurotransmission and behavior”
Abstract: The ventral tegmental area (VTA) participates in different aspects of motivated behavior, and our research has been conducted towards testing the hypothesis that the different roles ascribed to VTA are mediated by distinct subsets of neurons that through specific circuitry integrate information from specific neurons from different brain areas. At the cellular level, studies of VTA information processing have, for a long time, been focused on resident dopamine neurons, and more recently on local inhibitory GABA neurons. However, for more than 10 years, we have been providing evidence for the existence of glutamate neurons in the VTA, glutamate neurons that project in parallel to some of the same brain structures as the dopamine neurons and begun to determine their role in
behavior. By combination of classical and emerging anatomical techniques, we have found that VTA glutamate neurons establish both local and long-range connections. By optogenetic behavioral studies, we have found that VTA glutamate neurons throughout selective synapses play roles in reward, aversion, or social behavior. In the process, we have identified different subclasses of VTA glutamatergic neurons, some of them co-release dopamine and others co-release GABA. As part of this talk, I’ll present some our findings on co- release of neurotransmitters and proposed models for co-release of glutamate and dopamine, as well as co-release of glutamate and GABA.

Organizers
Nara I. Muraro – Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-MPSP – naramuraro@gmail.com
Esteban J. Beckwith – Instituto de Fisiología Biología Molecular y Neurociencias (IFIByNE)-UBA-CONICET – estebanbeck@gmail.com

Speakers:

Daniela Noain Department of Neurology, University Hospital Zurich Switzerland https://www.neuroscience.uzh.ch/en/research/sleep_and_sleep_disorders.html – https://www.sleep.uzh.ch/en.html  – Daniela.Noain@usz.ch
Could modulation of brain slow oscillatory activity become a new treatment alternative for Parkinson’s disease? Lessons learnt from animal studies.
Intro: Parkinson’s disease (PD) is characterized by damaging intracellular α-synuclein (αSyn) deposition that propagates extracellularly contributing to disease spread. Intracellular αSyn is sensitive to degradation, whereas extracellular αSyn may be eliminated by glymphatic clearance, a process shown in rodents to be increased during slow-waves sleep (SWS). Also, SWS appears to be closely linked with the velocity of motor symptoms progression and pharmacologically enhancing SWS results in objectively and subjectively improved sleep scores in PD patients. Here, we explored whether long-term slow-wave modulation in murine models of PD presenting αSyn aggregation alters pathological protein burden and, thus, might constitute a valuable therapeutic target.
Approach: We exerted slow-waves enhancement in VMAT2-deficient and A53T mouse models of PD by twice daily administration of sodium oxybate (200mg/kg, p.o.) 5 days/week for 4 months.
Slow-waves deprivation in VMAT2-deficient mice consisted of 16h/day sleep deprivation using the platform-over-water method. We then performed a variety of histopathological, immunofluorescence, biochemical, and molecular assessments over brain samples from sleep-modulated healthy and PD mice to assess αSyn protein load and the potential mechanisms associated to its alteration upon sleep modulation. Results: Sleep-modulating treatments showed
that enhancing slow waves in both VMAT2-deficient and A53T mouse models of PD reduced pathological αSyn accumulation compared to control animals. Non-pharmacological sleep deprivation had the opposite effect in VMAT2-deficient mice, severely increasing the pathological burden. Regarding potentially involved mechanisms, we found that SWS enhancement via sodium oxybate was associated with increased recruitment of aquaporin-4 to perivascular sites, suggesting a possible increase of glymphatic function. Furthermore, mass spectrometry data revealed differential and specific upregulation of functional protein clusters linked to proteostasis upon slow-wave-enhancing interventions. Take-home message: Overall, the beneficial effect of pharmacological SWS enhancement on neuropathological outcome in murine synucleinopathy models mirrors findings in models of Alzheimer and encourage further preclinical and clinical studies unravelling the potential of sleep-based interventions as therapeutic strategy in PD. Outlook: We are currently implementing at preclinical and clinical level non-pharmacological SWS-enhancing approaches with increased specificity and scalability. Our efforts intend to help pave the way to novel therapeutic implementations for neurodegenerative diseases characterized by protein accumulation in the mid-term.

María Juliana Leone Universidad Torcuato Di Tella Argentina – mleone@utdt.edu
School start times, chronotype, sleep and academic success in Argentinian adolescents Human physiology, behavior and performance show daily fluctuations. Light, social cues, culture and age modulate the properties of circadian rhythms. Even though humans are active during the day and rest at night, the phase of entrainment under light-dark conditions (i.e. chronotype) differs between individuals and it also changes with age. Importantly, chronotype is delayed during adolescence, but school start times continue starting very early in the morning. This ‘perfect storm’ becomes a ‘perfect hurricane’ in Argentina, where the cultural habits are later than in many other countries. In the last years, we have been studying the impact of school schedules on chronotype, sleep and academic success of adolescents of different ages who were randomly assigned to one of three school timings (starting at 07:45, 12:40 or 17:20) at the beginning of their secondary school. In this talk, I will present results from our previous and current cross-sectional and longitudinal studies, where we evaluated how chronotype and sleep change along adolescence, and how the interplay between chronotype and school schedules affect sleep and school success on Argentinian adolescents.

Giorgio Gilestro Department of Life Sciences, Imperial College London United Kingdom https://lab.gilest.ro/  – g.gilestro@imperial.ac.uk
Divergent evolution of sleep homeostasis open new perspectives on the function of sleep.
Sleep is a highly conserved behaviour among the animal kingdom, appearing in species as distant as jellyfishes and elephants. Understanding what drives this evolution and which traits are universal implies understanding what sleep really is and what it does. This is the ultimate question in the field.
It is generally believed that sleep serves a crucially important yet mysterious “core function” that is shared among all animals and that drives its evolution, but the evidence behind this hypothesis is lacking. In my talk, I will challenge this idea by telling the surprising story of how sleep evolved in seven different species of the Drosophila subgenus. We show that those aspects of sleep that are believed to be universal – such as its homeostatic regulation – are in fact only present in D. melanogaster and not in the other six Drosophila species we tested. We show that the difference in sleep homeostasis between melanogaster and the other species can be explained by a different underpinning cell-biology regulating synaptic strength upon prolonged wakefulness, at the same
time providing a possible evolutionary mechanism and reinforcing the connection between sleep homeostasis and synaptic strength.

Luis de Lecea Stanford University United States – https://med.stanford.edu/delecea/home.html – llecea@stanford.edu
Sleep and wake control across lifespan
The arousal construct underlies a spectrum of behaviors that include sleep, exploration, feeding, sexual activity and adaptive stress. Pathological arousal conditions include stress, anxiety disorders, and addiction. In the past few years we have used optogenetics to interrogate neuronal circuits underlying transitions between arousal states. Here I will present causal evidence of a critical period during adolescence in which disruption of sleep/wake cycles associated with increased dopaminergic tone results in deficits in social interactions in adult mice. I will also present a new mechanism underlying sleep fragmentation during aging. Hypocretin (hcrt) neurons are hyperexcitable in aged mice. We identified a potassium conductance known as the M-current, as a critical player in maintaining excitability of Hcrt neurons. Genetic disruption of KCNQ channels in Hcrt neurons of young animals results in sleep fragmentation. In contrast, treatment of aged animals with a KCNQ channel opener restores sleep/wake architecture. Finally, I will talk about our recent work demonstrating that focused ultrasound differentially affects excitatory vs inhibitory neurons in deep brain structures, paving the way to non-invasive neuromodulation of subcortical circuits in humans.

Organizer
Soledad Gonzalo Cogno – Kavli Institute for Systems Neuroscience and Centre for Algorithms in the Cortex, NTNU, Trondheim, Norway.
Email: soledad.g.cogno@ntnu.no

Symposium summary
During the second half of the 20th century, discoveries like orientation selectivity in the visual cortex and spatial selectivity in the entorhinal-hippocampal circuit were major breakthroughs that greatly advanced our understanding of how individual neurons encode features of the external world in their spiking activity. Yet, a long history of theoretical work suggests that brain function emerges from the collective activity of large neuronal populations. Most of these theories, however, have remained untestable due to the lack of technologies to probe neural circuits, and therefore the mechanisms underlying neuronal computation at the circuit level remain elusive. This landscape of uncertainty is now coming to an end, since technological advances from the last decade are making it possible to record from hundreds to thousands of cells simultaneously, and to perturb neural networks with single-cell resolution. These unprecedented advances are calling for an integrative approach where experimental and theoretical neuroscience are combined to understand how large neuronal populations compute. The main goal of this symposium is to take a step in that direction and present four complementary examples of how we can probe the inner mechanisms of neural circuits to understand emerging computations.

Speakers

With this symposium we bring together scientists from diverse areas of Neuroscience who share the common goal of elucidating the mechanisms that underlie brain function through the lens of interdisciplinary research and with a focus on neuronal circuits computation. Ranging from fully theory to a combination of modelling and experimental work, the speakers were carefully selected to guarantee gender balance (50% of the speakers and male and 50% are female) and a balance in seniority levels.

Inés Samengo– Department of Medical Physics and Instituto Balseiro of Centro Atómico Bariloche, CONICET, Argentina
Title: The emergence of a metric in the representation of space from neuronal population activity
Abstract: The firing probability of sensory neurons changes with the value of the stimulus they are sensitive to. Moreover, continuous modifications of the stimulus typically produce continuous distortions of the population activity probability distribution. Mathematically, this selectivity induces a metric in the space of stimuli that reflects their discriminability in terms of the population activity they evoke. This talk discusses how a metric of physical space emerges from the population activity of both place and grid cells. The properties of the metric depend on the number of cells in the population, on their intrinsic dynamics, and on the way they tile the space of stimuli. We conclude that the subjective metric is only Euclidean if the relative phases of the grid cells of a given module obey a mathematical relation dictated by the shape of the single-cell firing distribution. Deviations from this pattern give rise to representations in which physical space is not Euclidean.

Iván Davidovich – Edmond and Lily Safra Center for Brain Sciences and Racah Institute of Physics, The Hebrew University of Jerusalem, Israel
Title: Uncovering functional connectivity in continuous attractor networks
Abstract: Recent technologies enable large scale recordings, offering a unique opportunity to elucidate network connectivity from spiking activity. This task is challenging in general, because correlations between the neurons might arise which are not due to direct connections. In particular, continuous attractor network models (CANs), which have been used to model a wide range of brain functions, suffer from this issue and it has been argued that reliably estimating connectivity for them is not possible. We explore different approaches to connectivity inference in a simulated system of this kind and show that accounting for the patterns of global covariation encoded in the low-dimensional attractor manifold can reveal features of the true connectivity. We also highlight the importance of evaluating the credibility of our inference process, particularly in systems with rigid correlation structures. Our inference methods could be generalized to other systems operating on low-dimensional manifolds.

Emilio Kropff – Leloir Institute – IIBBA/CONICET, Argentina
Title: Unique potential of immature adult-born neurons for the remodeling of CA3 spatial maps
Abstract: Mammalian hippocampal circuits undergo extensive remodeling through adult neurogenesis. While this process has been widely studied, the specific contribution of adult-born granule cells (aGCs) to spatial operations in the hippocampus remains unknown. Here we show that optogenetic activation of 4-week-old (young) aGCs in free-foraging mice produces a non-reversible reconfiguration of spatial maps in proximal CA3, while rarely evoking neural activity. Stimulation of the same neuronal cohort on subsequent days recruits CA3 neurons with increased efficacy but fails to induce further remapping. In contrast, stimulation of 8-week-old (mature) aGCs can reliably activate CA3 cells but produce no alterations in spatial maps. Our results reveal a unique role of young aGCs in remodeling CA3 representations, a potential that can be depleted and is lost with maturation. This ability could contribute to generate orthogonalized downstream codes supporting pattern separation.

Soledad Gonzalo Cogno – Kavli Institute for Systems Neuroscience and Centre for Algorithms in the Cortex, NTNU, Trondheim, Norway.
Title: Minute-scale periodic sequences in the medial entorhinal cortex
Abstract: The medial entorhinal cortex (MEC) hosts many of the brain’s circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience. While location is known to be encoded by a plethora of spatially tuned cell types in this brain region, little is known about how the activity of entorhinal cells is tied together over time. In MEC, theta and gamma oscillations provide temporal structure to the neural population activity at subsecond time scales. It remains an open question, however, whether similarly powerful coordination occurs in MEC at behavioural time scales, in the second-to-minute regime. Here we show that MEC activity can be organized into a minute-scale oscillation that entrains nearly the entire cell population, with periods ranging from 10 to 100 seconds. The oscillation sometimes advanced uninterruptedly for tens of minutes, transcending epochs of locomotion and immobility. Throughout this ultraslow oscillation, neural activity progresses in periodic and stereotyped sequences. By combining the experimental data with training of recurrent neural networks we probe the mechanisms underlying the stereotyped sequences and the conditions under which the ultraslow oscillation is robust in presence of perturbations. We further show that the MEC sequences may have the potential to serve as a scaffold for processes that unfold at behavioural time scales.

IBRO Symposium

Organizer:

Marta C. Antonelli. Instituto de Biología Celular y Neurociencia “Prof. Dr. Eduardo De Robertis”. Facultad de Medicina. UBA. Argentina. mca@fmed.uba.ar.

Symposium summary:

Pregnancy is a significant time in women´s life but it can also be very challenging. During the gestational period, women like any other subject can be exposed to endogenous and exogenous challenges that may be perceived as unpleasant, aversive or threatening in such a way that the homeostasis, wellbeing and overall health is threatened. If stress persists during the nursing period, it will lead to deficient parenting interfering with the mother-infant attachment. This implies that during critical periods of brain development, i.e., pregnancy and nursing periods, the baby is subjected to environmental negative influences known to shape developmental trajectories, including neuronal connections. This apparently healthy baby, if exposed to a repeated stressful situation later in life, may show impairments in the functional development of affective and reward circuits, cognition, and response inhibition.  We understand that the relevance of this symposium is that it will bring together five neuroscientists geographically distant with long lasting background on the stress and resilience field to discuss the effects of perinatal insults on neurodevelopmental and neuroendocrinological programming.

Speakers:

Gerlinde A.S. Metz. WebSite: https://www.ulethbridge.ca/artsci/neuroscience/dr-gerlinde-alexandra-metz
Canadian Centre for Behavioural Neuroscience. Department of Neuroscience. University of Lethbridge. Lethbridge, Alberta, Canada. Department of Obstetrics & Gynecology, University of Alberta, Edmonton, Alberta, CANADA.
Title: “Impacts of Prenatal and Transgenerational Stress on Brain Development”

William P. Fifer. Website: https://www.columbiapsychiatry.org/profile/william-fifer-phd
Department of Pediatrics, Columbia University Medical Center, New York, New York.USA.
Title: “Adverse exposures affect maternal, fetal and infant sleep and subsequent neurobehavioral development”

José Alonso Fernández-Guasti.  Website: https://farmacobiologia.cinvestav.mx/Personal-Acad%C3%A9mico/Dr-Jos%C3%A9-Alonso-Fern%C3%A1ndez-Guasti
Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, MEXICO.
Title: “Prenatal stress and endocrine milieu as factors influencing sexual preference”

Bea R.H. Van den Bergh.  Health Psychology Research Group, University of Leuven (KU Leuven), Tiensestraat 102, Leuven. Belgium.
Title: “Prenatal exposure to maternal anxiety is associated with white matter microstructure and cognition in 28-year old offspring”

Silvia M. Lobmaier .Virtual. Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, GERMANY.
Title: “Fetal heart rate variability responsiveness to maternal stress”

(Auditorio)
Chair:
Guntram Bauer, Human Frontier Science Program
Marina Picciotto, Yale University, USA

Insights from the molecular functional level to understand why implementing the alpha7 nicotinic receptor as a therapeutic drug target is so challenging
 Cecilia Bouzat, INIBIBB, Bahía Blanca, Buenos Aires, Argentina
From zebrafish to rats: the role of nicotinic receptors in behaviours
Patricio Iturriaga-Vásquez, Universidad de la Frontera, Chile
Structure and function meet at the nicotinic receptor-lipid interface
Francisco Barrantes, CONICET, Argentina
Acetylcholine signaling relevant to anxiety and depression
Marina Picciotto, Yale University, USA

Supported by Human Frontier Science Program

Organizers
Leandro Casiraghi
Diego Golombek
UdeSA, UNQ, CONICET

Abstract:

Very often the temporal variable is ignored or only slightly considered in experimental science. In particular, neuroscience focuses on “where” phenomena occur, their duration and intensity (“how much”), and, eventually, on their underlying mechanisms (“how”), while the “when” is often diluted in the experimental design or statistics. However, time can offer an irrefutable source of independent variation on our data, in all fields of research of the brain and of behavior. In consequence, considering the time of the day, lighting patterns, seasonality, or the sleep/wake status of the study subjects or experimental preparations is fundamental for the understanding of our research object.

In this symposium, we invite the SAN community to consider “time” in their experiments and research in their experimental designs, the environmental conditions, and the analysis and interpretation of their results. Temporal variation, in its different dimensions (from milliseconds to seasons) is fundamental for neuroscience. To illustrate this, examples will be presented representing different fields within the study of the nervous system and behavior, going from the neural basis of rhythms in metabolism and feeding, the regulation of fear-related circuits, photic and non-photic pathways mediating behavior, and the consideration of sleep as a fundamental factor modulating virtually all neurophysiologic variables.

Speakers:

• Victoria Acosta-Rodríguez. UT Southwestern Medical Center Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, victoria.acosta@utsouthwestern.edu. PhD, Universidad Nacional de Córdoba.

• Haghani A, Lu AT,Li CZ, Robeck TR, Belov K, Breeze CE, Brooke RT, Clarke S, Faulkes CG, Fei Z, Ferguson SH, Finno CJ; Gladyshev VN, Gorbunova V; Goya RG, Hogan AN, Hogg CJ, Hore TA, Kiaris H, Kordowitzki P, Takahashi J.S, Acosta-Rodríguez VA et al. “DNA Methylation Networks Underlying Mammalian Traits”. Science (en revisión) 
• Acosta-Rodríguez VA, Rijo-Ferreira F, Izumo M, Xu P, Wight-Carter M, Green CB & Takahashi JS (2022). “Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice”. Science; 376(6598):1159-1160. 
• Rijo-Ferreira F, Acosta-Rodríguez V, Abel J, Kornblum I, Bento I, Kilaru G, Klerman E, Mota M & Takahashi JS (2020). “The malaria parasite has instrinsic rhythms”. Science;368(6492):746-753.
• Acosta-Rodríguez VA, de Groot MHM, Rijo-Ferreira F, Green CB, and Takahashi JS. (2017). “Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System”. Cell Metab; 5;26(1):267-277.e2.

Diego Fernández, Cincinatti Children’s Hospital Medical Center, diegofil3@gmail.com. Ph D, Universidad de Buenos Aires

• Weil T, Daly K, Castillo H, Thomsen M, Wang H, Mercau ME, Hattar S, Tejeda H, Fernandez DC. Daily changes in light influence mood via inhibitory networks within the thalamic perihabenular nucleus Science Advances, 2022 Jun 10;8(23) 
• Fernandez DC*, Komal R, Langel J, Ma J, Duy P, Penzo M, Zhao H, Hattar S*. Retinal innervation tunes circuits that drive non-photic entrainment to food. Nature, 2020, 581(7807):1-5. 
• Fernandez DC*, Fogerson P, Ospri L, Layne R, Akasako M, Singer J, Berson D, Hattar S*. Light affects mood through a novel retina-brain circuit. Cell, 2018, Sep 20;175(1):71-84.e18. 
• Fernandez DC, Chang Y, Hattar S, Chen S. Architecture of retinal projections to the central circadian pacemaker PNAS, 2016, 113(21):6047-52 

Ivana Bussi (University of Washington.) ivanabussi@gmail.com PhD. Universidad Nacional de Quilmes.

• Padilla S.L., Perez J.G., Ben-Hamo M., Johnson C.W., Sanchez R.E.A., Bussi I.L., Palmiter R.D., De La Iglesia H.O. “Kisspeptin neurons in the arcuate nucleus of the hypothalamus orchestrate circadian rhythms and metabolism”. Current Biology 29(4):592-604.e4, 2020.
• Sanchez R.E.A., Bussi I.L., Ben-Hamo M., Caldart C., Catterall W., De La Iglesia H.O. “Circadian Regulation of Sleep in a Pre-Clinical Model of Dravet Syndrome: Dynamics of Sleep Stage and Siesta Re-entrainment”. Sleep 42 (12), zsz173, 2019.
• Acosta J., Bussi I.L., Esquivel M., Hotch C., Golombek D.A., Agostino P.V. “Circadian modulation of motivation in mice”. Behavioural Brain Research 382, 112471, 2020. 
• Bussi I.L., Sanchez R.A.E., De La Iglesia H.O. “Vasopressin Neurons: Master Integrators of Time and Homeostasis”. Trends in Neuroscience 43 (11): 839-841, 2020.

Esteban Beckwith (IFIByNE, FCEN, UBA) estebanbeck@gmail.com PhD, Universidad de Buenos Aires

• Crystal M Vincent*, Esteban J Beckwith*, Carolina J Simoes da Silva, William H Pearson, Katrin Kierdorf, Giorgio F Gilestro, Marc S Dionne. “Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster” PLoS Pathog. 2022. doi: 10.1371/journal.ppat.1010826.
• Saloni Rose, Esteban J Beckwith, Charlotte Burmester, Robin C May, Marc S Dionne and Carolina Rezaval.  “Pre-copulatory reproductive behaviours are preserved in Drosophila melanogaster infected with bacteria”. Proc. R. Soc. B. 2022 DOI: 10.1098/rspb.2022.0492.
• Alice S. French, Quentin Geissmann, Esteban J. Beckwith and Giorgio F. Gilestro. “Sensory processing during sleep in Drosophila melanogaster”. Nature. 2021. DOI: 10.1038/s41586-021-03954-w.
• Esteban J. Beckwith* and Alice S. French. “Sleep in Drosophila and Its Context”. Frontiers in Physiology. 2019. DOI: 10.3389/fphys.2019.01167. 
• Quentin Geissmann*, Esteban J. Beckwith* and Giorgio F. Gilestro. “Most sleep does not serve a vital function. Evidence from Drosophila melanogaster” Science Advances. 2019. DOI: 10.1126/sciadv.aau9253.

Program:

• Acosta-Rodriguez, V. Circadian Rhythms in Aging and Longevity

Caloric restriction (CR) without malnutrition promotes health and longevity in mammals, yet the mechanisms are poorly understood. We previously reported that classic CR protocols not only reduce the total intake, but also induce chronic cycles of 2-hour feeding and 22-hour fasting in mice. Thus, it was unclear whether calories, fasting or feeding time could independently contribute to longevity. To disentangle this, we tested a control group fed ad libitum (AL) vs five 30% CR protocols varying how often and when mice had access to food. We included classic CR protocols in which mice consumed their allotment as a single meal in less than 2h at the beginning of the day or night (CR-day and CR-night), or smaller meals distributed over 12h (CR-day-12h and CR-night-12h), or evenly spread out throughout 24h (CR-spread) to avoid nocturnal-biased feeding pattern adopted by nocturnal rodents. We found that CR alone, without fasting, extends lifespan by 10%. However, longevity benefits are boosted to 20% if any fasting period is present and to 35% when feeding/fasting cycles match their natural clock-driven activity. Transcriptomic analysis in the liver under AL show that with aging, inflammation and metabolic pathways are up and downregulated, respectively. In the longest-lived group, night-feeding reduces such aging- related alterations, maintains robust 24h oscillations in gene expression at older ages, and improves glucose and hormonal homeostasis. We also identified genes sensitive to caloric intake, fasting, and feeding time. Our results demonstrate that circadian interventions promote longevity and provide a novel perspective to further explore mechanisms of aging.

• Diego C. Fernandez. Environmental light influences behavior through distinct retina-brain circuits

Animal physiology is profoundly modulated by daily changes in light. In mammals, light is detected by the retina and routed to brain areas. Among them, visual centers drive image-forming functions, whereas a wide range of retino-recipient brain targets process light signals to control innate processes, including sleep/wake cycles, metabolism, and affective behavior. In the lab we apply a curiosity-driven approach to address some of the following questions: What are the mechanisms and the neuronal circuits that allow us to extract time information from changes in light? Are these mechanisms similar to those that generate an internal representation of the visual scene? Can lighting conditions affect the way the brain communicates with other systems? What are the processes that govern the development and maturation of circuits processing environmental signals? The information obtained from this basic approach becomes particularly relevant for investigating the neural basis of disorders linked to deleterious environmental factors, such as light pollution and circadian disruption. Therefore, elucidating the pathways by which irregular light exposure impacts brain homeostasis would expand the opportunities to develop innovative therapeutics strategies, including non-pharmacological interventions. In a broader view, understanding how artificial lighting sources affect our physiology is critical in the design of better lighting conditions for improving human health and the environmental impact.

• Ivana L. Bussi. Fear keeps my mice awake during the day.

Circadian rhythms are behavioral and physiological rhythms with a period close to 24hs. They can be synchronized by stimuli of different nature, being the light-dark cycle the most powerful synchronizer in mammals. Fearful stimuli, such as the threat of predation, are likely to appear with a 24h periodicity. We hypothesized that cycling fearful stimuli presented during the active phase of the mice could lead to a shift in the temporal distribution of behavior.

To mimic more natural conditions in the lab, we built a set up consisting of a nesting area separated from a foraging area from which animals need to seek all their food and water. The foraging area can be rendered dangerous by applying an aversive stimulus, mild electric foot shocks. Throughout different experiments, we timed foot shocks to match the active phase or the resting phase in mice subjected to different light conditions. We showed that when random foot shocks are delivered in a 12-h window during the active phase, mice switch the phase of their foraging and home-cage activity to the opposite “safe” phase. Upon release into constant conditions mice continue foraging and feeding with the same phase as when the fearful stimulus was present. Taken together these results suggest that cyclic fear not only acts as a synchronizer of circadian rhythms in mice but also leaves a time stamp on a circadian oscillator, resetting the phase of foraging and home-cage activity behavior. This concept is particularly important for memory and learning research as it incorporates a new variable to be considered at the time of performing fear conditioning tasks in mice.

• Esteban Beckwith. Social interactions impact sleep and the clock 

A large number of species have a social organization, where the interaction with other conspecifics is crucial for the individual and the specie. Social interactions perceived as positive are associated with improved health. Conversely, social isolation has been shown to negatively affect behaviour and health. In particular, increased aggression, anxiety, food consumption, changes in activity levels, and deficits in learning and memory are all consequences of a socially impoverished environment. In humans, the perception of being excluded from social interaction is sufficient for an increase in neural activity and leads to poor sleep quality, which in turn leads to a large number of physiological and behavioural deficits. Like in humans, the negative consequences of social isolation are observed in other social species. 

Drosophila melanogaster has become essential for exploring the neurobiological bases of behaviour. Recent work has established that this fly is a social animal. Drosophila flies form non-stochastic interaction networks, which depend on chemical cues, both gustatory and olfactory, use social information to modulate decision making, are capable of training their circadian clock using social cues, and establish hierarchies among males. All this has shown that the social context imposes relevant changes in physiology and behaviour, and enables the use of this model to explore behavioural and social strategies that are adaptive for the species, as well as their genetic and molecular bases. 

In this presentation, I will discuss results from the laboratory where we show that the social context modulates locomotion, sleep and can set the pace of the circadian clock. 

Chairs:
Daniella Agrati – dagrati@fcien.edu.uy Sección Fisiología, Facultad de Ciencias. Universidad de la República. Uruguay.
Natalia Uriarte – natiuria@fcien.edu.uy Laboratorio de Neurociencias, Facultad de Ciencias. Universidad de la República. Uruguay.

Symposium summary

Sexual and maternal behaviors are highly conserved among mammals. These affiliative behaviors are characterized by proximity seeking between individuals, which reflects their strong motivational basis. The neuroendocrine basis of these reproductive behaviors have been extensively studied in the laboratory rat as a reference model, however much remains yet to be understood about the complexity of their regulation.

The objective of this symposium is to look at sexual and maternal behaviors, beyond the standard conditions of study, in more challenging reproductive contexts and models, to deepen our analysis of their complexity. To this aim, the symposium will bring together neuroscientists from different geographic regions focused on the study of sexual and maternal behaviors in the female rat in non-classical reproductive periods, such as adolescence and litter overlapping, and models of pathologies, such as diabetes and depression. We expect that this conjunction of experimental approaches will promote discussion and critical analysis of current and future research directions, as well as regional collaborations.

Speakers:

Daniella Agrati. Sección Fisiología, Facultad de Ciencias, Universidad de la República. Uruguay.
Title: “Development of sexual motivation in the female rat throughout adolescence”.
Abstract: In-person presentation: This talk will describe the maturation of female rat sexual motivation and behavior throughout adolescence employing different behavioral models. It will also delve into the possible role of sex steroids – their levels and receptor expression in the sexual neural circuitry- in this developmental process.

Alonso Fernández-Guasti. Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, México.
Titlte: “Alterations in the sexual behavior of diabetic female rats”
Abstract: In-person presentation: This talk will focus on the alterations in the expression of sexual behavior and motivation of female rats in a streptozotocin-induced model of diabetes mellitus type 1 and type 2. It will also deepen into the effect of insulin treatment on these behavioral deficits and the changes in the activation of the sexual neural circuit that may underlie them.

Mariana Pereira. Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, Estados Unidos.
Tiltle: “How mothers mother? Neurobiology of Maternal Sensitivity”.
Abstract: In-person presentation: This talk will focus on the neurobiological mechanisms that allow mothers to dynamically coordinate caregiving decisions to resolve the constantly changing needs of their offspring, as well as to provide mechanistic insight into how maternal sensitivity is compromised by postpartum depression.

Natalia Uriarte. Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República. Uruguay.
Title: “Flexibility in behavioral strategies of mother rats raising pups of different ages”.
Abstract: In-person presentation: This talk will focus on the behavioral and cognitive adaptations that mothers exhibit while caring for their offspring in challenging reproductive contexts such as the overlapping litter model in the rat. Emphasis will be placed on the neural basis underlying this behavioral flexibility.

Organizer

Alejandro Schinder – Fundación Instituto Leloir Buenos Aires, Argentina
E-mail: aschinder@leloir.org.ar 

Symposium summary

Brain function relies on the establishment of proper circuits occurring during development, followed by the subsequent ability to refine and rewire specific neuronal connections according to environmental and physiological requirements. Multiple regions of the cortex maintain the capacity for remodeling, expressing mechanisms that are already present in the developing brain, such as activity-dependent synaptic modification. This symposium will present three distinct examples of cortical remodeling that illustrate the dynamic capacity for activity-dependent modification. Guillermina Lopez-Bendito will tell us about the refinement of thalamic projections reaching the barrel cortex that occurs during perinatal development. Dan Shulz will share his latest discoveries on the plasticity in the adult somatosensory cortex using a brain-machine interphase (BMI) approach where barrel cortex maps become rewired over time to control a mechanical arm. Alejandro Schinder will talk about remodeling of hippocampal networks through the integration of adult-born neurons, a process that is largely modulated by the activity of local circuits.

Speakers

Guillermina López-Bendito Institute of Neuroscience (IN), Developmental Neurobiology Unit, Alicante, Spain
Title: Development and Plasticity of Sensory Circuits
Abstract Our research team runs several related projects studying the cellular and molecular mechanisms involved in the development of axonal connections in the brain. In particular, our aim is to uncover the principles underlying thalamocortical axonal wiring, maintenance and ultimately the rewiring of connections, through an integrated and innovative experimental programme. The development of the thalamocortical wiring requires a precise topographical sorting of its connections. Each thalamic nucleus receives specific sensory information from the environment and projects topographically to its corresponding cortical. A second level of organization is achieved within each area, where thalamocortical connections display an intra-areal topographical organization, allowing the generation of accurate spatial representations within each cortical area.

Therefore, the level of organization and specificity of the thalamocortical projections ismuch more complex than other projection systems in the CNS. The central hypothesis of our laboratory is that thalamocortical wiring influences and maintains the functional architecture of the brain. We also believe that rewiring and plasticity events can be triggered by activity-dependent mechanisms in the thalamus. In this talk, I will present our recent data on the activity-dependent mechanisms involved in sensory circuits development and how these circuits acquire sensory-modality specificity. I will also present data on the role of thalamic spontaneous activity in promoting neuroplastic cortical changes following sensory deprivation. Within these projects we are using several experimental programs, these include optical imaging, manipulation of gene expression in vivo, cell and molecular biology, biochemistry, cell culture, sensory deprivation paradigms and electrophysiology.

Daniel E. Shulz Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Saclay, France
Title: Probing tactile feature encoding, sensori-motor integration and neuronal plasticity in mice through a cortical closed-loop brain-machine interface
Abstract: Tactile information is acquired and processed in the brain through concerted interactions between movement and sensation. We study neuronal processes responsible for the coding of sensorimotor information by using a comprehensive approach including electrophysiological, imaging, optogenetic and behavioral strategies in rodents. We use this knowledge to implement  sensory feedback injected to the brain for improving the motor control of a brain machine interface.

Alejandro Schinder Fundación Instituto Leloir, Buenos Aires, Argentina
Activity-dependent integration of developing neurons of the adult hippocampus
Abstract: Learning and memory involve a delicate balance between networks capable of persistent information storage and circuits that rewire to adapt to environmental demands or learn new behavioral traits. The hippocampus undergoes extensive rewiring due to its capacity to generate new neurons that will contribute with thousands of new connections, integrate within preexisting structures, and provide alternative paths for information processing. Neuronal growth in the adult hippocampus recapitulates aspects of perinatal development although at slower pace, demanding >8 weeks in the mouse dentate gyrus. Over this time, molecular identity, morphology, electrical properties and synaptic connections evolve dynamically towards a mature granule cell phenotype. This process results in developing neurons expressing distinct functional properties as they move towards maturation. In my talk I will discuss how different forms of activity influence neuronal maturation and function, present recent data on the molecular principles responsible for bringing neural stem cells through the pathway to granule cells, and share evidence on the role of developing neurons and their enhanced plasticity in spatial encoding in the hippocampus.