title: Dopamine Neurons Change the Type of Excitability in Response to Stimuli.
abstract: The dynamics of neuronal excitability determine the neuron's response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency "balanced" state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or co-activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I excitability in dopamine neurons might be important for low firing rates and fine-tuning basal dopamine levels, while switching excitability to type II during NMDAR and AMPAR activation may facilitate a transient increase in dopamine concentration, as type II neurons are more amenable to synchronization by mutual excitation.
authors.affiliation: Department of Physics, Indiana University, Bloomington, Indiana, United States of America.|Department of Mathematical sciences, Indiana University - Purdue University, Indianapolis, Indiana, United States of America.
authors.forename: Ekaterina O
authors.identifier: 0000-0001-9131-7756
authors.initials: EO
authors.lastname: Morozova
authors.affiliation: Institute of Applied Physics, Nizhny Novgorod, Russia.
authors.forename: Denis
authors.identifier: 0000-0003-4367-8965
authors.initials: D
authors.lastname: Zakharov
authors.affiliation: Group of Neural Theory, INSERM U960 LNC, IEC, Ecole Normale Superieure PSL University, Paris.|Center for Cognition and Decision Making, NRU HSE, Moscow, Russia.
authors.forename: Boris S
authors.initials: BS
authors.lastname: Gutkin
authors.affiliation: Addiction Neuroscience Program, Indiana University - Purdue University, Indianapolis, Indiana, United States of America.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Lapish
authors.affiliation: Department of Mathematical sciences, Indiana University - Purdue University, Indianapolis, Indiana, United States of America.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kuznetsov
mesh_terms: D002118:Calcium / Q000378:metabolism; D019295:Computational Biology; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000502:physiology*; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D012964:Sodium; D002118:Calcium; D004298:Dopamine