224 | Effect of leptin on mechanical sensitivity in Ob/Ob and WT mice.

Neural excitability, synaptic transmission and neuron-glia interactions

Author: Florencia Paz Correa | Email: florenciacorrea92@hotmail.com

Florencia Paz Correa , Verónica De la Fuente , Paula Perissinotti

1° Ifibyne (UBA, Conicet)

Leptin performs numerous actions in the brain. We reported that leptin has effects on somatosensory thalamic networks by decreasing GABAergic release from the thalamic reticular nucleus and the firing frequency of neurons in the Ventrobasal nucleus (VB). Electrophysiological recordings in the obese Ob/Ob mice supported that the development of the thalamocortical system in the absence of endogenous leptin decreases the functional expression of the HCN channel (H current) in the VB. This channel influences membrane properties and synaptic integration within a neuron circuit. In Ob/Ob mice, although they lack circulating leptin, the receptor remains functional. It is for this reason that by applying exogenous leptin, we expected to see a modification in the neuronal signals that relay somatosensory information (mechanical sensitivity, pain, itch) to the cortex. In this work, we cannulated the VB and injected leptin (1ug) in one hemisphere and vehicle in the other. Twenty-four hours later, we either performed patch clamp experiments or a behavioral study (Von Frey test) to assess the mechanical sensitivity of the animals. We found that leptin application increased the H-current density recorded in thalamocortical slices, thus restoring its dysregulation observed in the ob/ob mice (WT, n=9; Ob/Ob, n=7, ANOVA, p<0.05). The application of Leptin induced mechanical allodynia (2-way RMANOVA: genotype and treatment, WT: n=6, Ob/Ob: n=7, p=0.03 for treatment).