Electrical membrane properties of rat substantia nigra compacta neurons in an in vitro slice preparation

Kita, Takako; Kita, Hitoshi; Kitai, S.T.

doi:10.1016/0006-8993(86)91454-x

Cited by 176 publications

(111 citation statements)

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“…The physiological and pharmacological properties of these cells have been previously described for dopamine containing neurones of the midbrain in vitro (Llinas et al, 1984;Kita et al, 1986;Grace & Onn, 1989;Lacey et al, 1989;Yung et al, 1991;Hajos & Greenfield, 1993;Mercuri et al, 1995). Because no clear differences were observed between the effects of MAO inhibitors on neurones in the SNc and VTA the data were pooled.…”

Section: Resultsmentioning

confidence: 99%

Electrophysiological effects of monoamine oxidase inhibition on rat midbrain dopaminergic neurones: an in vitro study

Mercuri

Bonci

Siniscalchi

et al. 1996

British J Pharmacology

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1 The effects of the inhibition of monoamine oxidase (MAO) type A and B have been evaluated on the spontaneous firing activity of the dopaminergic (principal) neurones of the rat midbrain intracellularly recorded from a slice preparation. 2 The non-specific MAO inhibitor, pargyline, superfused at a concentration of 10-100 ,uM, decreased or abolished the spontaneous firing discharge of the principal neurones in the subtantia nigra pars compacta and ventral tegmental area. This effect had a slow onset and appeared to be sustained. 3 The administration of the dopamine D2/3 receptor antagonist, sulpiride (100-300 nM), antagonized the pargyline-induced effect, while the superfusion of the dopamine DI receptor antagonist, SCH 23390(1-3 pM) did not counteract the induced inhibition of the firing rate.4 The inhibitor for the MAO A, clorgyline (30-100 gM), reduced the firing rate of the dopaminergic neurones. A similar depressant effect was also observed when a MAO B inhibitor, deprenyl (30-100 gM), was applied. Lower concentrations of both drugs (300 nM-10 gM) did not produce consistent effects on neuronal discharge. 5 Our data suggest that only the blockade of both types of MAO enzymes favours the inhibitory action of endogenous dopamine on somato-dendritic D2/3 autoreceptors.

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Section: Resultsmentioning

confidence: 99%

Electrophysiological effects of monoamine oxidase inhibition on rat midbrain dopaminergic neurones: an in vitro study

Mercuri

Bonci

Siniscalchi

et al. 1996

British J Pharmacology

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“…The subthreshold Ca 2+ -K + oscillatory mechanism underlies the generation of low frequency background firing in a significant subpopulation of DA neurons [7][8][9][10][11][12][13][14][15][16][17][18]51]. However, a number of studies suggest a contribution of Ca 2+ -independent currents to oscillations [26,19,25,27,46].…”

Section: Influence Of Intrinsic Currents On the Type Of Excitabilitymentioning

confidence: 99%

“…The type of excitability is determined by the internal properties of the currents contributing to pacemaking in the DA neuron. L-type Ca 2+ and SK-type Ca 2+ -dependent K + currents are the core currents that traditionally constitute this mechanism [7][8][9][10][11][12][13][14][15][16][17][18] (but see the section on the mechanisms of DA neuron pacemaking). However, our model shows that the mechanism results in type II excitability, in which a hyperpolarizing current blocks the voltage oscillations without restoring a low frequency.…”

Section: The Role Of the Subthreshold Sodium Currentmentioning

confidence: 99%

“…However, it is still a matter of on-going debate in the literature since different experimental results lead to contradicting conclusions, proposing that different currents are critical for the DA neuron spontaneous firing. In a number of experimental and modeling studies it has been shown that spontaneous tonic firing relies on the interactions between the voltage gated calcium (Ca 2+ ) and SK-type Ca 2+ -dependent potassium (K + ) currents [7][8][9][10][11][12][13][14][15][16][17][18][19]. Wilson and Callaway [4] and later Chan et al [19] showed that calcium-driven slow oscillatory potentials (SOPs) drive the spiking rate of the SNc DA neurons.…”

Section: Mechanisms Of Da Neuron Pacemakingmentioning

confidence: 99%

“…The current composition producing low-frequency pacemaking in DA neurons is of vibrant debate among researchers in the field. A number of experimental [7][8][9][10][11][12][13][14][15][16][17][18][19] studies suggests that the maintenance of tonic firing in at least a subpopulation of DA neurons relies on the interactions of the voltage gated calcium (Ca 2+ ) and SK-type Ca 2+ -dependent potassium (K + ) currents Slow pacemaking in our model relies on a subthreshold Ca 2+ -K + oscillatory mechanism, similar to a number of well-established models [4,[20][21][22][23][24]. Interaction between Ca 2+ and Ca 2+ -dependent K + currents periodically brings the neuron to the spike threshold and generates a metronomic firing pattern.…”

Section: Introductionmentioning

confidence: 99%

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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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Tranylcypromine, but not moclobemide, prolongs the inhibitory action of dopamine on midbrain dopaminergic neurons: An in vitro electrophysiological study

Mercuri

Federici

Marinelli

et al. 2000

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Electrical membrane properties of rat substantia nigra compacta neurons in an in vitro slice preparation

Cited by 176 publications

References 16 publications

Electrophysiological effects of monoamine oxidase inhibition on rat midbrain dopaminergic neurones: an in vitro study

Electrophysiological effects of monoamine oxidase inhibition on rat midbrain dopaminergic neurones: an in vitro study

Dopamine neurons change the type of excitability in response to stimuli

Tranylcypromine, but not moclobemide, prolongs the inhibitory action of dopamine on midbrain dopaminergic neurons: An in vitro electrophysiological study

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