Chapter 17 Neurotransmitter receptors and ionic conductances regulating the activity of neurones in substantia nigra pars compacta and ventral tegmental area

doi:10.1016/S0079-6123(08)61351-5

Progress in Brain Research

Volume 99, 1993, Pages 251-276

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The use of in vitro electrophysiological techniques has permitted new vistas to be opened onto the ionic and receptor mechanisms subserving synaptic transmission in dopamine neurones, as in other areas of mammalian brain. Functional correlates of receptors described previously by neurochemical techniques have been demonstrated; also functional receptors have been demonstrated whose existence was little suspected (muscarinic and glycinekaurine). An interesting, but perhaps less well established phenomena includes the synergy between CCK and dopamine, the idea that ligand-gated potassium channels may also be sulphonylurea-sensitive and ATP-gated and that NMDA receptor activation may cause an outward current due to an ion exchange pump. Although not all studies have attempted to discriminate between substantia nigra and VTA, where comparisons are possible there is as yet very little reason to suppose that mesolimbo-cortical dopamine neurones, originating in the VTA, possess either different membrane properties or neurotransmitter receptors from nigrostriatal neurones. Their basic electrophysiological characteristics appear the same, both for dopamine and non-dopamine interneurones; dopamine cells from both the areas are hyperpolarized by D₂ receptor activation, but not affected by opioids, whereas the reverse is true for non-dopamine cells; dopamine cells from both regions are depolarized by acetylcholine acting on both nicotinic and muscarinic receptors; and they all receive synaptic input mediated by GABA, acting on GABA_A and GABA_B receptors, and glutamate (or aspartate), acting on NMDA and non-NMDA type receptors.

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Cell Types in the Different Nuclei of the Basal Ganglia
2016, Handbook of Behavioral Neuroscience
Citation Excerpt :
For example, in the rat striatum only a minority of the predominant medium-sized spiny neurons (Table 5.1) are active at any one time, with active neurons widely separated (Wickens, 1993; Wilson and Groves, 1981). By contrast, the SN consists of projection neurons that are larger (Table 5.1) and exhibit tonic or pacemaker-like activity (Lacey, 1993; Nakanishi et al., 1987). The pacemaker-like activity for the SN is evident for both the dopamine neurons of the SNc (Lacey, 1993) (see chapter: Neurophysiology of Substantia Nigra Dopamine Neurons: Modulation by GABA and Glutamate) and the GABA neurons of the SNr (Nakanishi et al., 1987) (see chapter: The Substantia Nigra Pars Reticulata).
The past 15–20 years has yielded considerable new knowledge on the different types of neurons and interneurons within the basal ganglia. This chapter reviews the new knowledge, along with the historical knowledge. Key topics and their functional consequences reviewed include: (1) the existence of local inhibitory connections between neighboring striatal spiny projection neurons, and between striatal interneurons and projection neurons, (2) new knowledge on the absolute number of neurons, interneurons, and astrocytes within the basal ganglia, and associated structures such as the lateral habenula, using modern stereological methods, and (3) newly identified striatal interneurons and external globus pallidus projection neurons. The new anatomical and electrophysiological knowledge has advanced understanding of information processing within the basal ganglia and associated structures. Technical advances in serial sectioning and image collection for electron microscopy, and in optogenetics and transgenic mouse/rat lines to identify specific neuronal subpopulations, may facilitate future progress.
Neurophysiology of Substantia Nigra Dopamine Neurons: Modulation by GABA and Glutamate
2016, Handbook of Behavioral Neuroscience
Citation Excerpt :
Most of the afferents to the SN are GABAergic, and at least 70% of the synapses formed on nigral DA neurons are GABAergic (Bolam and Smith, 1990; Gulley and Smithberg, 1971; Ribak et al., 1976; Rinvik and Grofova, 1970). Both GABAA and GABAB receptors have been identified on DA neurons (Lacey, 1993; Lacey et al., 1988; Sugita et al., 1992). Stimulation of each type, both in vivo and in vitro, produces an inhibitory response although with different time courses and ionic bases (Cameron and Williams, 1993; Engberg et al., 1993; Lacey et al., 1988).
The nigrostriatal dopamine (DA) system is crucial to a large array of behaviors ranging from voluntary motor function to higher cognitive processes. Nigrostriatal neurons in vivo fire in three distinct patterns, modulated by afferent input. At least 70% of the inputs to nigral DA neurons are GABAergic, arising from the striatum, the globus pallidus, the rostromedial tegmental nucleus, and axon collaterals from the substantia nigra pars reticulata (SNr) projection neurons. Manipulation of these inputs, in particular those originating in SNr, produces dramatic effects on nigrostriatal neuron firing patterns. Since many or most of the afferents to the substantia nigra synapse on both nigrostriatal DA neurons and SNr GABAergic projection neurons, the response of nigral DA neurons to both excitatory and inhibitory afferents reflects a complex interplay between the intrinsic properties of the nigrostriatal neurons, the patterns and rate of the afferent input, and the synaptic interactions between SNr GABAergic neurons and the nigrostriatal DA neurons.
Generating bursts (and pauses) in the dopamine midbrain neurons
2014, Neuroscience
Citation Excerpt :
Furthermore, the SK channel-mediated post-burst pauses might as well be activated by other G-protein-linked receptors that activate release of Ca2+ from stores, including the α-adrenergic receptor and muscarinic acetylcholine receptor. Both GABAA and GABAB receptors have been identified on DA neurons (Lacey et al., 1988; Sugita et al., 1992; Lacey, 1993). Stimulation of each type, both in vivo and in vitro, produces an inhibitory response although with different time courses and ionic bases (Lacey et al., 1988; Cameron and Williams, 1993; Engberg et al., 1993).
Dopamine (DA) midbrain neurons project to several striatal and cortical target areas and are essentially involved in a puzzling variety of important brain functions such as action selection and motor performance, motivation and reward-based learning, but also working memory and cognition. These neurons act via the release of their (main) neurotransmitter, dopamine, which binds to metabotropic dopamine receptors of the D1 or D2 type on target neurons. Axonal but also dendritic dopamine release is essentially controlled by calcium-triggered exocytosis of dopamine-filled synaptic vesicles primarily driven by electrical activity of the dopamine neuron, which generates patterns of actions potentials in the somato-dendritic domain and distributes them along its axonal tree. Thus, recording the behaviorally relevant pattern of electrical activity in DA neurons and identifying the underlying biophysical mechanisms that integrate afferent synaptic inputs and intrinsic excitability constitute a crucial element for defining the physiological roles of the midbrain DA system. Electrical activity of midbrain DA neurons in vivo is characterized by tonic background activity in a narrow frequency range (ca. 1–8 Hz) interrupted by either transient (i.e. phasic, <500 ms) sequences of high-frequency firing (>15 Hz), so called “bursts”, or transient pauses of electrical activity, where DA neurons generate no action potentials. This review focuses on the properties of these phasic activity changes in midbrain DA neurons. It updates recent progress on the expanding behavioral contexts, associated with phasic electrical activity in DA neurons beyond the classical (canonical) reward prediction error model. The review also highlights recently defined contributions of synaptic inputs for burst and pause generation and the roles of distinct postsynaptic ion channels in midbrain DA neurons.
Microinjections of a dopamine D1 receptor antagonist into the ventral tegmental area block the expression of cocaine conditioned place preference in rats
2014, Behavioural Brain Research
Stimulation of dopamine (DA) D1 receptors in the ventral tegmental area (VTA) is involved in primary rewards. In the current study we investigated whether VTA D1 receptor stimulation likewise plays a role in mediating the rewarding effects of cocaine-associated stimuli, using the cocaine conditioned place preference (CPP) paradigm. Rats were prepared with cannulae so as to allow microinjections in the VTA and later conditioned to a cocaine-associated environment using the CPP paradigm. Prior to each conditioning session rats were injected with either saline or cocaine (10 mg/kg, intraperitoneally) and then placed in one of the two sides of the CPP apparatus. Sessions lasted 30 min a day over a period of eight days, such that rats alternated daily between consistently experiencing cocaine in one side and saline in the other. On the test day, which was conducted one day after conditioning, rats were given bilateral microinjections of one of four doses of the D1 antagonist, SCH 23390, (0, 2, 4 or 8 μg/0.5 μl) directly into the VTA and allowed free access to both sides of the apparatus. Preference for either side was measured as time spent in each side and compared to the same measures taken before conditioning. The D1 antagonist produced a dose-related, significant reduction in the preference for the cocaine-paired side compared to vehicle. These data suggest that the expression of cocaine conditioned place preference requires stimulation of VTA D1 receptors and, as such, are the first to suggest a role for VTA dendritically released DA in cocaine-, or other reward-, related learning.
Cell Types in the Different Nuclei of the Basal Ganglia
2010, Handbook of Behavioral Neuroscience
Citation Excerpt :
With respect to neuronal activity rate, the dominant population of GABA neurons within the SNr are able to fire spontaneously at high frequency and are tonically activated by excitatory glutamatergic neurons of the STN (Nakanishi et al., 1987; Bevan et al., 1994). Within the SNc, its dominant population of dopamine neurons seem to sustain pacemaker-like firing that is intrinsically generated, as well as bursting activity when stimulated (Lacey, 1993). By contrast, only a minority of the predominant population of GABA medium-spiny neurons within the striatum are thought to be activated at any one point in time (Wickens, 1993).
This chapter reviews that the basal ganglia (BG) can be subdivided into dorsal and ventral aspects. The dorsal aspect of the basal ganglia in rodents and higher vertebrates consists of four major nuclei. These nuclei are the striatum, the globus pallidus, the subthalamic nucleus (STN) and the substantia nigra (SN). The striatum in rodents is a single nucleus, also called the caudateputamen. In higher vertebrates the striatum is comprised of the caudate nucleus and the putamen, which are partitioned by the internal capsule. The globus pallidus consists of external (GPe) and internal (GPi) segments. In rodents, the external segment is also known as the globus pallidus and the internal segment is equivalent to the entopeduncular nucleus. The chapter discusses that GPe is used when referring to the rodent globus pallidus and GPi is used when referring to the rodent entopeduncular nucleus. Each pallidal segment has different afferents and efferents and is functionally unique. The SN is also divided into two parts that are functionally distinct. The pars reticulata (SNr) and the pars compacta (SNc) share mostly similar afferents but have different outputs. The main output of the SNr is to the thalamus, while the SNc primarily consists of dopaminergic neurons that principally innervate the striatum. The SNr and GPi are the major output nuclei of the basal ganglia. Cconsiderable knowledge on the different types of neurons and interneurons in the basal ganglia has been gained in the past 10–15 years. There has also been an advance in knowledge of the absolute number of neurons, interneurons and astrocytes within the dorsal aspect of the basal ganglia, as well as the absolute number of neurons in associated structures.
Ethanol Action on Dopaminergic Neurons in the Ventral Tegmental Area. Interaction with Intrinsic Ion Channels and Neurotransmitter Inputs
2010, International Review of Neurobiology
The dopaminergic system originating in the midbrain ventral tegmental area (VTA) has been extensively studied over the past decades as a critical neural substrate involved in the development of alcoholism and addiction to other drugs of abuse. Accumulating evidence indicates that ethanol modulates the functional output of this system by directly affecting the firing activity of VTA dopamine neurons, whereas withdrawal from chronic ethanol exposure leads to a reduction in the functional output of these neurons. This chapter will provide an update on the mechanistic investigations of the acute ethanol action on dopamine neuron activity and the neuroadaptations/plasticities in the VTA produced by previous ethanol experience.

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Chapter 17 Neurotransmitter receptors and ionic conductances regulating the activity of neurones in substantia nigra pars compacta and ventral tegmental area

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Brain Res.

Cell Signal

Neuroscience

Brain Res.

Neuron

Brain Res.

Neuroscience

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Neuroscience

Brain Res.

Brain Res.

Neuroscience

Trends Pharmacol. Sci.

Trends Pharmacol. Sci.

Neuroscience

Brain Res.

Brain Res.

Neuropharmacology

Brain Res.

Neuropeptides

Neurosci. Lett.

Eur. J. Pharmacol.

Neuroscience

Neuroscience

Neuroscience

Brain Res.

Brain Res.

Neuroscience

Neuroscience

Biochem. Biophys. Res. Commun.

Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.

Neuroscience

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Brain Res.

Behav. Brain Res.

M-currents and other potassium currents in bullfrog sympathetic neurones.

J. Physiol., (Lond.)

Dopamine “autoreceptors”: pharmacological characterisation by microiontophoretic single cell recording studies.

Naunyn Schmiedebergs Arch. Pharmacol.

Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K+ channels.

Science

Ultrastructural localisation of tyrosine hydroxylase in the rat ventral tegmental area: relationship between immunolabelling density and neuronal associations.

J. Neurosci.

Acetylcholine activates an inward current in single mammalian smooth muscle cells.

Nature

The cholinergic innervation of the rat substantia nigra: a light and electron microscopic immunohistochemical study.

Exp. Brain Res.

Inositol phosphates and cell signalling.

Nature

Dopamine-containing systems in the CNS.

Catecholaminergic brain stem regulatory systems.

Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K⁺ channels.