The interplay of seven sub-threshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

GERMAN MATO; YIMY AMARILLO; MARCELA NADAL; BERNARDO RUDY; EDWARD ZAGHA

JOURNAL OF NEUROPHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2014

0022-3077

P { margin-bottom: 0.08in; direction: ltr; color: rgb(0, 0, 0); widows: 2; orphans: 2; }A:link { color: rgb(0, 0, 255); } The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at sub-threshold potentials. Using patch clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven sub-threshold ion currents of TC neurons and quantify their individual contribution to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing Ih, IT and INaP move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady activation of IA and IKir. Using the computational model we show that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. Three amplifying variables (activation of IT, activation of INaP and activation of IKir) and three recovering variables (inactivation of IT, activation of IA and activation of Ih) determine the propensity ?or lack thereof? of TC neurons to fire bursts repetitively. The specific roles that of each of these variables play during the intrinsic oscillation were also determined.