Altered HCN channel function in thalamic ventrobasal neurons of leptin-deficient mice

ROCHA, AGUSTIN; KARGIEMAN, LUCILA; URBANO, FRANCISCO J.; PERISSINOTTI, PAULA P.; GROSSO, TOMAS

CABA

Congreso; XXXV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2020

The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel is a voltage-gated ion channel that carry the H-current (IH). The expression of HCN1-4 isoforms is abundant in the thalamus. This channel is activated at sub-threshold potentials and works as an intrinsic and slow voltage-clamp that tends to stabilize the resting membrane potential, regulating the neuronal excitability and the synaptic integration. Leptin is a pleiotropic hormone that regulates numerous CNS functions. The dense distribution of leptin receptor mRNA in the thalamus suggests that leptin could act as a neuromodulator of thalamocortical activity. Here, we studied the electrophysiological expression of IH in ventrobasal (VB) neurons in brain slices from wildtype (WT) or the leptin-deficient mouse (ob/ob). IH density was increased by 22% in WT females compared to WT males. However, IH density was altered regardless of the gender in the ob/ob mice. Similarly, IH density decreased by 22% in ob/ob males (WT, n=23; ob/ob, n=22) and 16% in ob/ob females (WT, n=14; ob/ob, n=11). The time constant of deactivation was slower in the ob/ob compared to the WT for either males or females. In order to study whether IH alterations could be reversed, leptin was injected in vivo through a cannula implanted in the VB nucleus of ob/ob mice. We found that 24 hours after injecting leptin, IH density reached values as observed in WT, confirming that alterations of HCN channel function could be reversed by leptin.