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

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

Congreso; https://san2020.saneurociencias.org.ar/; 2020

INTRODUCTION 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. It is involved in many neuron-level functions, which include regulation of membrane resistance, selective filtering for coincident inputs, modulation of intrinsic cellular frequency characteristics. Obesity is characterized by disrupted sleep architecture and sleep/wake disturbances (Dixon et al. 2007; Laposky et al. 2006; Vgontzas et al. 1998). Leptin deficient mice display a mutation in the ?obese? gene (i.e., homozygous ob/ob mice), develop severe obesity after the fifth postnatal week and manifest impaired sleep consolidation (Laposky et al. 2006). The thalamocortical (TC) system is the neuronal substrate of rhythmic synchronized activity during slow wave sleep. TC neurons display an intrinsic pacemaker activity, which is synchronized throughout the thalamocortical network (Steriade et al., 1997). IH underlying pace-maker activity and its regulation is considered an important mechanism for the control of rhythmic burst firing during the sleep-wake cycle. 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).