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

CORREA, FLORENCIA; RODRIGUEZ, NAZARENA; URBANO, FRANCISCO J.; PERISSINOTTI, PAULA P

Congreso; SAN; 2022

The ventrobasal (VB) is the main somatosensory projection nucleus in the thalamus. Our group reported trophic effects of leptin on the murine thalamocortical somatosensory 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 stems from their unique ability to influence membrane properties such as resting membrane potential (RMP) and input resistance, which in turn are important for determining a given neuron’s role within a circuit. Using the "whole-cell patch-clamp" technique in mice thalamocortical slices, we observed that simultaneous blocking of HCN (30 M ZD7288) and K2P (3 mM Ba2+) channels produced an aberrant and spontaneous firing of VB neurons. Over the concentration range 0.5 to 3 mM, Ba2+ blocks some K2P channels. Blockade of the L-type calcium channels by nitrendipine (1 M) was able to terminate this rhythmic and aberrant firing. We found that development of the thalamocortical system in the absence of endogenous leptin alters the functional expression of HCN and K2P channels in the VB nucleus. HCN current decreased by 22% (n=23, 22) whereas the K2P current increased by 70% (n=5, 5). A fine balance between HCN and K2P channels could regulate neuronal intrinsic excitability. In fact, the transmission mode was increased in VB neurons from the ob/ob.