Theoretical and Computational Neuroscience
Author: Paula Patricia Perissinotti | Email: peripali@gmail.com
Paula Perissinotti1°2°, Andreas Neef3°
1° Instituto de Fisiologia, Biologia Molecular y Neurociencias (IFIBYNE-CONICET)
2° Departamento de Fisiologia, Biologia Molecular y Celular “Prof. Hector Maldonado”. Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Argentina
3° Institute for Dynamics of Biological Networks of the Georg-August University Göttingen, Germany
Leptin deficiency during the development of thalamocortical system has neurotrophic implications (DOI: 10.1007/s00429-018-1645-x). Electrophysiological recordings from brain slices reveal that leptin absence alters the functional expression of the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel, the T-type calcium channel and the Kv7 (M-type) channel in the ventrobasal (VB) nucleus of the thalamus. VB neurons from ob/ob mice display increased excitability and reduced capacitance compared to WT mice.
We integrated into single theoretical model of the VB neuron all experimentally obtained properties of HCN, T-, and M-type channels, along with changes in capacitance. Simulations were conducted using the NEURON simulation environment and the Python programming language. All simulations were performed at room temperature (24°C). Each compartment was modeled using the conductance-based Hodgkin-Huxley equations. Temperature-dependent ionic mechanisms were integrated into these neuron morphologies, including sodium channels (Nav and Nap), leak channels, potassium channels (Kv1, Kv3, Kv7, BK, Kir, A-type, SK, TREK), calcium channels (high-threshold [HVA], low-threshold [LVA] T-type), HCN channels, and calcium clearance mechanisms.
The development of this in silico model of a single VB neuron allows us to characterize how changes in current density and/or localization (somatic/dendritic) of HCN, T-type, and M channels impact neuronal excitability in mouse models.