Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting

Morozova, Ekaterina

doi:10.25006/ia.4.s2-a18.10

Cited by 7 publications

(27 citation statements)

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“…The biophysical model of the DA neuron is a conductance-based one-compartmental model modified from [91] where v is the voltage and c m is the membrane capacitance. There are eight intrinsic currents of the DA neuron: a calcium current ( I Ca ), a calcium-dependent potassium current ( I KCa ), a potassium current ( I K ), a direct rectifier current ( I DR ), a subthreshold sodium current ( I sNa ), a hyperpolarization-activated current ( I h ), a fast sodium current ( I Na ), and a leak current ( I leak ).…”

Section: Methodsmentioning

confidence: 99%

“…Since the GABA neurons powerfully modulate DA neuron activity via direct, monosynaptic inhibitory connections [55,97–100], one can expect multiple GABA neurons to make connections with a single DA neuron. Second, we found that our results are valid for a wide range of the number of GABA neurons and start to change only if the number becomes small (10 or lower) [91]. …”

Section: Methodsmentioning

confidence: 99%

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Dopamine Neurons Change the Type of Excitability in Response to Stimuli

et al. 2016

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dopamine Neurons Change the Type of Excitability in Response to Stimuli

et al. 2016

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show abstract

“…Since the GABA neurons powerfully modulate DA neuron activity via direct, monosynaptic inhibitory connections [55,[97][98][99][100], one can expect multiple GABA neurons to make connections with a single DA neuron. Second, we found that our results are valid for a wide range of the number of GABA neurons and start to change only if the number becomes small (10 or lower) [91].…”

Section: Synaptic Inputsmentioning

confidence: 76%

“…The biophysical model of the DA neuron is a conductance-based one-compartmental model modified from [91] …”

Section: Methodsmentioning

confidence: 99%

Dopamine neurons change the type of excitability in response to stimuli

Morozova

Zakharov²,

Gutkin

et al. 2016

Preprint

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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 coactivation 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. Author SummaryDopamine neurons play a central role in guiding motivated behaviors. However, complete understanding of computations these neurons perform to encode rewarding and salient stimuli is still forthcoming. Network connectivity influences neural responses to stimuli, but so do intrinsic excitability properties of individual neurons, as such properties define synchronization qualities and neural coding strategy. We investigated the excitability type of the DA neuron and found that, depending on the synaptic and intrinsic current composition, DA neurons can switch from type I to type II excitability. In short, without synaptic inputs or under balanced excitatory and inhibitory inputs DA neurons exhibits type I excitability, w...

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“…These two types of cells as constituents of the 'ventral tegmental area microcircuit model challenges the classical view that GABA neurons exclusively reduce dopamine neuron firing and bursting' [13] . DA and GABAergic cells are distinguished by both action and membrane potential (AP and MP) properties as the former exhibits robust sag that is absent in the latter [14] .…”

Section: Vta Da Neuronsmentioning

confidence: 87%

Addictive neurons

2018

Ther Targets Neurol Dis

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Since the reward center is considered to be the area tegmentalis ventralis of the hypothalamus, logically its neurons could mainly be responsible for addiction. However, the literature asserts that almost any neurons of CNS can respond to one or another addictive compound. Obviously not only addictive nicotine, but also alcohol, amphetamine, cannabis, cocaine, heroin and morphine may influence dopaminergic cells alone in VTA. Moreover, paradoxically some of these drugs ameliorate symptoms, counterbalance syndromes, cure diseases and improve health, not only those related to the CNS and in adults, but also almost all other organs and in children, e.g. epilepsy.

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Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting

Cited by 7 publications

References 0 publications

Dopamine Neurons Change the Type of Excitability in Response to Stimuli

Dopamine Neurons Change the Type of Excitability in Response to Stimuli

Dopamine neurons change the type of excitability in response to stimuli

Addictive neurons

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