Electrophysiological and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat

Richards, Christopher D.; Shiroyama, Takashi; Kitai, S.T.

doi:10.1016/s0306-4522(97)00093-6

Cited by 222 publications

(241 citation statements)

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“…To date, in vitro electrophysiological studies have considered DA midbrain neurons mainly as a single population (Pucak and Grace, 1994;K itai et al, 1999), which shows low-frequency pacemaker activity, broad action potentials followed by a pronounced afterhyperpolarization, and a pronounced sag component that is mediated by hyperpolarization-activated, cyclic nucleotide-regulated cation (I h , HC N) (for review, see Santoro and Tibbs, 1999) channels (Sanghera et al, 1984;Grace and Onn, 1989;Lacey et al, 1989;Richards et al, 1997). However, in vivo studies have highlighted f unctional differences between subgroups of DA neurons (Wilson et al, 1977;Chiodo et al, 1984;Greenhoff et al, 1988;Shepard and German, 1988;).…”

mentioning

confidence: 99%

I_hChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

et al. 2002

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Dopaminergic (DA) midbrain neurons in the substantia nigra (SN) and ventral tegmental area (VTA) are involved in various brain functions such as voluntary movement and reward and are targets in disorders such as Parkinson's disease and schizophrenia. To study the functional properties of identified DA neurons in mouse midbrain slices, we combined patchclamp recordings with either neurobiotin cell-filling and triple labeling confocal immunohistochemistry, or single-cell RT-PCR. We discriminated four DA subpopulations based on anatomical and neurochemical differences: two calbindin D 28 -k (CB)-expressing DA populations in the substantia nigra (SN/CBϩ) or ventral tegmental area (VTA/CBϩ), and respectively, two calbindin D 28 -k negative DA populations (SN/CBϪ, VTA/CBϪ). VTA/ CBϩ DA neurons displayed significantly faster pacemaker frequencies with smaller afterhyperpolarizations compared with other DA neurons. In contrast, all four DA populations possessed significant differences in I h channel densities and I h channel-mediated functional properties like sag amplitudes and rebound delays in the following order: SN/CBϪ 3 VTA/ CBϪ 3 SN/CBϩ 3 VTA/CBϩ. Single-cell RT-multiplex PCR experiments demonstrated that differential calbindin but not calretinin expression is associated with differential I h channel densities. Only in SN/CBϪ DA neurons, however, I h channels were actively involved in pacemaker frequency control. In conclusion, diversity within the DA system is not restricted to distinct axonal projections and differences in synaptic connectivity, but also involves differences in postsynaptic conductances between neurochemically and topographically distinct DA neurons.

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confidence: 99%

I_hChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

et al. 2002

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“…Although the majority of the dopaminergic somata in substantia nigra are in the pars compacta, there exist scattered groups of dopaminergic neurons within pars reticulata. However, the morphology and physiology of these neurons appear identical to those of the pars compacta dopaminergic neurons (Richards et al, 1997).…”

Section: Introductionmentioning

confidence: 84%

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

2004

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“…Lobb et al [70] modified our previous model [24] to capture the balance of the inhibition and excitation and disinhibition bursts. In these models, a high maximal frequency (>10 Hz) can be achieved by tonic activation of the AMPAR or in response to depolarizing current injection, which contradicts experimental observations [7,34]. To the contrary, a number of experimental studies suggest that stimulation of NMDA receptors evokes a burst of high-frequency firing, whereas AMPA receptor activation evokes modest increases in firing [37][38][39][40] (but see [61,71]).…”

Section: Related Studies Of Nmda-gaba Balance In Da Neuronsmentioning

confidence: 92%

“…Intrinsic firing frequencies of these neurons were set to a range of 12-22 Hz, similar to what is observed experimentally [34,102,103]. The activity of each GABA neuron contributes to the activation of the GABAR current entering the DA neuron by increasing the gating variable according to the equation…”

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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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Electrophysiological and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat

Cited by 222 publications

References 89 publications

I_hChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

I_hChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

Dopamine neurons change the type of excitability in response to stimuli

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Electrophysiological and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat

Cited by 222 publications

References 89 publications

IhChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

IhChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

Dopamine neurons change the type of excitability in response to stimuli

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I_hChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

I_hChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain