V-098
Kv7 channel dysfunction and HCN channel modulation shape excitatory synaptic integration in thalamocortical circuits under leptin deficiency.
Sergio Daniel Manterola1,2, Agustin Patxot2, Nicolas Moral Mazzeo2, Francisco Jose Urbano1,3, Paula Patricia Perissinotti1,3
  1. Instituto de Fisiologia, Biologia Molecular y Neurociencias (IFIBYNE-UBA-CONICET)
  2. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires
  3. Departamento de Fisiolofia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires
Presenting Author:
Sergio Daniel Manterola
sdmanterola@yahoo.com.ar
This study investigates how Kv7 potassium channel dysfunction and modulation of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels influence excitatory synaptic integration in ventrobasal (VB) thalamic neurons of leptin-deficient obese (ob/ob) mice versus wild-type (WT). HCN channels mediate the hyperpolarization-activated Ih current, which stabilizes resting membrane potential and input resistance. Electrophysiological recordings from brain slices of WT and ob/ob mice were used to characterize AMPA receptor kinetics (τ1 ≈ 1.19 ms, τ2 ≈ 1.22 ms) as well as Kv7 and HCN levels, which were then incorporated into a realistic multicompartmental NEURON model. AMPA receptors were placed at the dendritic level and activated using a stochastic event generator. WT and ob/ob models were tested under varying Kv7 and HCN conductances. WT responses remained stable, whereas ob/ob neurons—due to Kv7 dysfunction—exhibited heightened sensitivity, with spike output strongly modulated by HCN alterations. In ob/ob neurons, impaired Kv7 function reduces subthreshold stabilization, making excitability highly dependent on HCN activity. This interaction amplifies synaptic variability and responsiveness, suggesting disrupted sensory processing in obesity-related pathophysiology. These findings highlight the critical Kv7-HCN interplay in maintaining excitability stability and implicate their dysfunction as a potential mechanism underlying thalamocortical alterations in obesity.