The domain of neuronal firing on a plane of input current and conductance.
The activation of neurotransmitter receptors increases the current flow and membrane conductance and thus controls the firing rate of a neuron. In the present work, we justified the two-dimensional representation of a neuronal input by voltage-independent current and conductance and obtained experimentally and numerically a complete input-output (I/O) function. The dependence of the steady-state firing rate on the input current and conductance was studied as a two-parameter I/O function. We employed the dynamic patch clamp technique in slices to get this dependence for the whole domain of two input signals that evoke stationary spike trains in a single neuron (Ω-domain). As found, the Ω-domain is finite and an additional conductance decreases the range of spike-evoking currents. The I/O function has been reproduced in a Hodgkin-Huxley-like model. Among the simulated effects of different factors on the I/O function, including passive and active membrane properties, external conditions and input signal properties, the most interesting were: the shift of the right boundary of the Ω-domain (corresponding to the exCitation block) leftwards due to the decrease of the maximal potassium conductance; and the reduction of the Ω-domain by the decrease of the maximal sodium concentration. As found in experiments and simulations, the Ω-domain is reduced by the decrease of extracellular sodium concentration, by cooling, and by adding slow potassium currents providing interspike interval adaptation; the Ω-domain height is increased by adding color noise. Our modeling data provided a generalization of I/O dependencies that is consistent with previous studies and our experiments. Our results suggest that both current flow and membrane conductance should be taken into account when determining neuronal firing activity.
Ioffe Physical-Technical Institute of the Russian Academy of Sciences, Politekhnicheskaya str., 26, 194021, St.-Petersburg, Russia. elena.smirnova@mail.ioffe.ru.
E Yu
EY
Smirnova
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
A V
AV
Zaitsev
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
K Kh
KKh
Kim
Ioffe Physical-Technical Institute of the Russian Academy of Sciences, Politekhnicheskaya str., 26, 194021, St.-Petersburg, Russia.|Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia.
A V
AV
Chizhov
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D001921:Brain / Q000166:cytology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D012964:Sodium; D011188:Potassium
Dynamic clamp; Firing rate; Hodgkin-Huxley model; Membrane parameters; Shunting; Two-dimensional neuronal input-output function