The interplay of seven sub - threshold conductances controls the resting membrane potential and the 4 oscillatory behavior of thalamocortical neurons

26 The signaling properties of thalamocortical (TC) 27 neurons depend on the diversity of ion conductance 28 mechanisms that underlie their rich membrane 29 behavior at sub-threshold potentials. Using patch 30 clamp recordings of TC neurons in brain slices from 31 mice and a realistic conductance-based 32 computational model, we characterized seven sub33 threshold ion currents of TC neurons and quantify 34 their individual contribution to the total steady-state 35 conductance at levels below tonic firing threshold. 36 We then used the TC neuron model to show that the 37 resting membrane potential results from the 38 interplay of several inward and outward currents 39 over a background provided by the potassium and 40 sodium leak currents. The steady-state conductances 41 of depolarizing Ih, IT and INaP move the membrane 42 potential away from the reversal potential of the 43 leak conductances. This depolarization is 44 counteracted in turn by the hyperpolarizing steady 45 state current of IA and IKir. Using the computational 46 model, we show that single parameter variations 47 compatible with physiological or pathological 48 modulation, promote burst firing periodicity. The 49 balance between three amplifying variables 50 (activation of IT, activation of INaP and activation of 51 IKir) and three recovering variables (inactivation of 52 IT, activation of IA and activation of Ih) determine 53 the propensity –or lack thereof– of repetitive burst 54 firing of TC neurons. We also determined the 55 specific roles that each of these variables have 56 during the intrinsic oscillation. 57