The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons.
The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions 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 (hyperpolarization-activated cationic current), IT (low-threshold calcium current), and INaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of IA (fast transient A-type potassium current) and IKir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between 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) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation.
Consejo Nacional de Investigaciones Científicas y Técnicas, Física Estadística e Interdisciplinaria, Centro Atómico Bariloche, San Carlos de Bariloche, Rio Negro, Argentina; Smilow Neuroscience Program, New York University Medical Center, New York, New York; and amarillo@cab.cnea.gov.ar.
Yimy
Y
Amarillo
Smilow Neuroscience Program, New York University Medical Center, New York, New York; and.
Edward
E
Zagha
Consejo Nacional de Investigaciones Científicas y Técnicas, Física Estadística e Interdisciplinaria, Centro Atómico Bariloche, San Carlos de Bariloche, Rio Negro, Argentina; Comisión Nacional de Energía Atómica, Centro Atómico Bariloche and Instituto Balseiro, San Carlos de Bariloche, Rio Negro, Argentina.
German
G
Mato
Smilow Neuroscience Program, New York University Medical Center, New York, New York; and.
Bernardo
B
Rudy
Consejo Nacional de Investigaciones Científicas y Técnicas, Física Estadística e Interdisciplinaria, Centro Atómico Bariloche, San Carlos de Bariloche, Rio Negro, Argentina;
Marcela S
MS
Nadal
D000200:Action Potentials; D000818:Animals; D008564:Membrane Potentials; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013787:Thalamic Nuclei / Q000166:cytology / Q000502:physiology*
D012964:Sodium; D011188:Potassium
repetitive burst firing; resting membrane potential; subthreshold conductances; thalamocortical neuron