049 | Functional evidence of immature neurons in the adult human hippocampus

Cellular and Molecular Neurobiology

Author: Mariela Fernanda Trinchero | Email: mftrinchero@gmail.com

Mariela F. Trinchero , Magalí Herrero , Sabrina Benas , Carlos A. Ciraolo , Emilio Kropff , María del Carmen García , Alejandro F. Schinder

1° Neuronal Plasticity Laboratory, Fundación Instituto Leloir, Buenos Aires, CONICET
2° Physiology and Algorithms of the brain Laboratory, Fundación Instituto Leloir, Buenos Aires, CONICET
3° Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

The generation of new granule cells (GCs) in the hippocampus is a remarkable form of plasticity that occurs in most mammals. The existence of this process in the human hippocampus has been investigated combining different techniques such as DNA labeling with thymidine analogs or 14C incorporation and, more recently, high-quality immunofluorescence and single-nucleus RNA sequencing that provided evidence for the presence of immature GCs. Approaching adult human neurogenesis from several standpoints is key to fully understand this extraordinary form of structural plasticity. In order to uncover functional evidence of developing GCs, we have set up a protocol for ex vivo electrophysiology in hippocampal slices from patients suffering intractable refractory epilepsy that result in the resection of this structure. Whole cell recordings from GCs belonging to 5 young adult patients showed that most neurons in the granule cell layer exhibit mature features. However, bioinformatic analysis revealed a small cluster of neurons with depolarized membrane potential, high input resistance, and decreased number of spikes elicited by current injection. GCs that belonged to this cluster also displayed a low frequency of excitatory postsynaptic currents, suggesting poor connectivity with entorhinal cortex afferents. Further histological analysis of these samples will unveil whether these immature functional properties correlate with the presence of immature neuronal markers.