Leptin deficiency leads to a functional dysregulation of HCN and potassium channels in the somatosensory thalamus of the mouse

CORREA FP; RODRIGUEZ N; URBANO FJ; PERISSINOTTI PP

Ciudada Autonoma de Buenos Aires

Congreso; XXVII Annual Meeting Sociedad Argentina de Investigación en Neurociencias (SAN); 2022

Sociedad Argentina de Investigación en Neurociencias (SAN)

The ventrobasal (VB) is the main somatosensory projection nucleus in the thalamus. Our group reported trophic effects of leptin on the murine thalamocortical sonatosensory circuit. The hyperpolarization- activated Cyclic Nucleotide-gated (HCN2/4) channel and members of the two-pore­ domain background potassium (K2P) Channel Family (TASK and TREK) are abundantly expressed in the thalamus. The pivotal function played by HCN and K2P channels sets from their unique ability to influence membrane properties such as resting membrane potential and input resistance, which in turn are important for determining a given neuron's rote within a circuit. Here, we studied the electrophysiological expression of HCN and K2P channels in VB neurons in thalamic slices from the leptin-deficient obese mouse (ob/ob). We observed that simultaneous blocking of HCN (30 uM ZD7288) and K2P (3 mM Ba2+) channels produced an aberrant and spontaneous firing of VB neurons, which was reverted after blocking L-type calcium channels (1 uM Nitrendipine). We found that development of the thalamocortical system in the absence of endogenous leptin altered the functional expression of HCN and K2P channels in the VB nucleus. HCN current decreased by 22°/o (n=23, 22; WT, ob/ob) whereas the K2P current increased by 70% (n=5,5; WT, ob/ob). A fine balance between HCN and K2P channels could regulate neuronal intrinsic excitability. In fact, the transmision mode was increased in VB neurons from the ob/ob.