Muscarinic receptors mediate direct inhibition of GABA release from rat striatal nerve terminals

doi:10.1016/0304-3940(90)90099-U

Neuroscience Letters

Volume 116, Issue 3, 24 August 1990, Pages 347-351

https://doi.org/10.1016/0304-3940(90)90099-U Get rights and content

Abstract

The effects of acetylcholine (ACh) on the depolarization-evoked release of [³H]γ-aminobutyric acid ([³H]GABA) have been investigated using synaptosomes prepared from rat corpus striatum and depolarized by superfusion with 9 mM KCl. Acetylcholine inhibited the [³H]GABA overflow in a concentration-dependent manner. The maximal effect was about 50%. The IC₅₀ value (concentration producing half-maximal effect) amounted to 1 μM, in the absence of acetylcholinesterase inhibitors. The effect of ACh on the K⁺-evoked [³H]GABA release was counteracted by the muscarinic receptor antagonist atropine, but not by the nicotinic receptor antagonist mecamylamine or by the selective M₁ antagonist pirenzepine. The data show that muscarinic receptors with low affinity for pirenzepine are localized on GABAergic nerve endings in rat corpus striatum where they may directly inhibit the release of GABA.

References (29)

S.G. Butcher et al.
Origin and modulation of acetylcholine activity in the neostriatum
Brain Res.
(1974)
D.L. Cheney et al.
Choline acetyltransferase activity and mass fragmentographic measurement of acetylcholine in specific nuclei and tracts of rat brain
Neuropharmacology
(1975)
J.A. Girault et al.
In vivo release of [³H]γ-aminobutyric acid in the rat neostriatum. I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents
Neuroscience
(1986)
M. Herkenham
Mismatches between neurotransmitter and receptor localizations in brain: observations and implications
Neuroscience
(1987)
F. Javoy et al.
Involvement of the dopamine nigrostriatal system in the picrotoxin effect on striatal acetylcholine levels
Brain Res.
(1977)
P.L. McGeer et al.
Neostriatal choline acetylase and cholinesterase following selective brain lesions
Brain Res.
(1971)
A. Pittaluga et al.
Studies on [³H]GABA and endogenous GABA release in rat cerebral cortex suggest the presence of autoreceptors of the GABA_B type
Eur. J. Pharmacol.
(1987)
M. Raiteri et al.
A simple apparatus for studying the release of neurotransmitters from synaptosomes
Eur. J. Pharmacol.
(1974)
F.O. Schmitt
Molecular regulators of brain function: a new view
Neuroscience
(1984)
A.N.M. Schoffelmeer et al.
Comparison between electrically evoked and potassium induced ³H-noradrenaline release from rat neocortex slices: role of calcium ions and transmitter pools
Neurochem. Int.
(1981)

J.C. Stoof et al.

GABA modulates the release of dopamine and acetylcholine from rat caudate nucleus slices

Eur. J. Pharmacol.

(1979)

C. Bianchi et al.

GABA induced changes in acetylcholine release from slices of guinea-pig brain

Naunyn-Schmiedeberg's Arch. Pharmacol.

(1982)

J.P. Bolam et al.

A type of aspiny neuron in the rat neostriatum accumulates [³H]gamma-aminobutyric acid: combination of Golgi-staining, autoradiography and electron microscopy

J. Comp. Neurol.

(1983)

J.T. Coyle et al.

Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea

Nature

(1976)

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Cholinergic regulation of GABAergic interneurons has been shown in a number of recent studies and cholinergic terminals have been found to innervate GABAergic interneurons, particularly FS interneurons (Chang and Kita, 1992). Collectively, acetylcholine acts to reduce evoked striatal GABAergic release via muscarinic receptors (Marchi et al., 1990; Raiteri et al., 1990). However, interaction with FS interneurons occurs via both nicotinic and muscarinic receptors in a complex manner.
Dystonia is a movement disorder of both genetic and non-genetic causes, which typically results in twisted posturing due to abnormal muscle contraction. Evidence from dystonia patients and animal models of dystonia indicate a crucial role for the striatal cholinergic system in the pathophysiology of dystonia. In this review, we focus on striatal circuitry and the centrality of the acetylcholine system in the function of the basal ganglia in the control of voluntary movement and ultimately clinical manifestation of movement disorders. We consider the impact of cholinergic interneurons (ChIs) on dopamine–acetylcholine interactions and examine new evidence for impairment of ChIs in dysfunction of the motor systems producing dystonic movements, particularly in animal models. We have observed paradoxical excitation of ChIs in the presence of dopamine D2 receptor agonists and impairment of striatal synaptic plasticity in a mouse model of DYT1 dystonia, which are improved by administration of recently developed M1 receptor antagonists. These findings have been confirmed across multiple animal models of DYT1 dystonia and may represent a common endophenotype by which to investigate dystonia induced by other types of genetic and non-genetic causes and to investigate the potential effectiveness of pharmacotherapeutics and other strategies to improve dystonia.
Giant GABA<inf>A</inf> receptor mediated currents in the striatum, a common signature of Parkinson's disease in pharmacological and genetic rodent models
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The former are silent and the latter display the same single-spike firing pattern in vitro before and after dopaminergic depletion [1]. The absence of effect by blockers of nicotinic or muscarinic cholinergic receptors and the similar tonic pattern of activity of cholinergic interneurons (TANs) observed both in the presence and absence of dopaminergic innervation [1] rules out any effect due to alteration of the presynaptic inhibition of GABA release by cholinergic receptors [2,3] or to TANs dysfunctioning [4]. We identified a similar GABAA signature in the striatum of 6- to 19-month-old PINK1 deficient mice.
Oscillatory giant GABA_A receptor-mediated currents recorded from medium spiny neurons (MSNs) of the striatum in vitro are an electrophysiological signature of dysfunctioning dopaminergic synaptic transmission. This is a common early signature of Parkinson's disease in pharmacological and genetic mice models. Recorded from at least 40% of MSNs, these currents are present both after and up to 10 months before motor signs, and are suppressed by chronic levodopa treatment or chronic lesion of the subthalamic nucleus. Giant GABA_A receptor-mediated currents may result from the diverse changes in the GABAergic striatal circuitry identified after dysfunction in dopaminergic transmission. Fast spiking (FS) interneurons are more strongly electrically coupled and a subpopulation of FS interneurons sprouts onto D2-type MSNs. On the other hand, low threshold spiking (LTS) interneurons shift to an excessive and recurrent bursting pattern. All these effects are likely to lead to profound dysfunction in the striatal GABAergic network, given that MSN responses to cortical inputs are highly dependent on GABAergic inputs and that GABAergic interneurons play a fundamental role in network oscillations.
Interaction between gamma-aminobutyric acid type A (GABA<inf>A</inf>) receptor agents and scopolamine in the nucleus accumbens on impairment of inhibitory avoidance memory performance in rat
2013, Behavioural Brain Research
Citation Excerpt :
The interaction between the cholinergic and GABAergic systems may also be reciprocal in nature. It has been shown that GABA inhibits striatal cholinergic interneurons [30,31], whereas acetylcholine (ACh) exerts both excitatory and inhibitory impact on GABAergic activity mediated by different muscarinic receptor subtypes [27,32,33]. It is unknown to what extent there exists a functional interaction between the GABAergic and cholinergic systems in the NAc to influence IA memory, although it has been suggested that there exists a mutual crosstalk between both GABAergic and cholinergic neurons in the NAc [34].
We designed this study to investigate effects of intra-nucleus accumbens (intra-NAc) infusions of GABA_A receptors agonist (muscimol) and antagonist (bicuculline) by themselves and their interaction with scopolamine on inhibitory avoidance (IA) memory performance. This study used a step-through IA task to assess memory in male Wistar rats. The results showed that post-training intra-NAc infusions of muscimol at doses of 0.01 and 0.02 μg/rat significantly impaired IA memory performance, while bicuculline (0.1, 0.2 and 0.4 μg/rat) had no effect. Post-training intra-NAc infusions of scopolamine at dose of 0.5 μg/rat impaired IA memory performance by itself, and in combination with an ineffective dose of muscimol increased impairment of IA memory performance. The results also showed that post-training intra-NAc infusions of bicuculline prevented the impairing effect of higher doses of scopolamine on IA memory performance. Pre-test intra-NAc infusions of muscimol (0.01 and 0.02 μg/rat) and bicuculline (0.001, 0.01 and 0.1 μg/rat) impaired IA memory performance. The results also revealed that pre-test intra-NAc infusions of scopolamine (0.25 and 0.5 μg/rat) impaired IA memory performance, and its co-infusions with an ineffective dose of muscimol (0.005 μg/rat) increased impairment of IA memory performance. Interestingly, pre-test intra-NAc infusions of bicuculline impaired performance by itself, but did not prevent the impairing effect of scopolamine. It can be concluded that GABA_A and muscarinic receptors of the NAc may have an interaction in modulation of IA memory performance, which may result from affecting output neurons in the NAc directly or indirectly via cholinergic and GABAergic interneurons.
Spontaneous firing and evoked pauses in the tonically active cholinergic interneurons of the striatum
2011, Neuroscience
Citation Excerpt :
Another disinhibitory route by which M1-type mAChRs increase the excitability of SPNs is by enhancing release of endocannabinoids postsynaptically from SPNs, which activate CB1 receptors presynaptically on GABAergic terminals thereby suppressing inhibition of SPNs (location 5 in Fig. 4) (Narushima et al., 2007). In contrast, activation of presynaptic mAChRs, primarily of the M2 type, reduces synaptic transmission both at glutamatergic synapses (location 3) (Akaike et al., 1988; Malenka and Kocsis, 1988; Higley et al., 2009) and at GABAergic synapses (location 6) (Marchi et al., 1990; Koos and Tepper, 2002). Of special interest is the effect of mAChRs on the cholinergic interneurons themselves via autoreceptors (location 7 in Fig. 4).
The tonically active neurons (TANs) are a population of neurons scattered sparsely throughout the striatum that show intriguing patterns of firing activity during reinforcement learning. Following repeated pairings of a neutral stimulus with a primary reward, TANs develop a transient cessation of firing activity in response to the stimulus, termed the “conditioned pause response.” In tasks where specific cues are arranged to signal the probability of particular outcomes, the pause response to both cue and outcome may differ in ways that suggest the involvement of different inputs to the same neuron. Here we review the cellular properties of cholinergic interneurons and describe the response to their afferents in terms of inducing TAN-like pauses in tonic firing. Recent work has shown that thalamostriatal inputs to cholinergic neurons transiently suppress firing activity via dopamine release. Because these pauses are initiated by subcortical pathways with limited sensory processing abilities, we propose that they are an ideal correlate for the pauses observed in TANs in response to cues signaling trial initiation. On the other hand, pauses that accompany outcome presentation contain higher-level information, including an apparent sensitivity to reward prediction error. Thus, these pauses may be mediated by cortical inputs to cholinergic interneurons. Although there is evidence linking cholinergic pauses to synaptic plasticity, much remains to be discovered about the effect of this relatively sparse but influential population on the striatal learning system.
This article is part of a Special Issue entitled: Function and Dysfunction of the Basal Ganglia.
The cholinergic system and neostriatal memory functions
2011, Behavioural Brain Research
The striatum is one of the major forebrain regions that strongly expresses muscarinic and nicotinic cholinergic receptors. This article reviews the current knowledge and our new findings about the striatal cholinoceptive organization and its role in a variety of cognitive functions. Pharmacological and genetic manipulations have indicated that the cholinergic and dopaminergic system in the striatum modulate each other's function. In addition to modulating the dopaminergic system, nicotinic cholinergic receptors facilitate GABA release, whereas muscarinic receptors attenuate GABA release. The striatal cholinergic system has also been implicated in various cognitive functions including procedural learning and intradimensional set shifting. Together, these data indicate that the cholinergic system in the striatum is involved in a diverse set of cognitive functions through interactions with other neurotransmitter systems including the dopaminergic and GABAergic systems.
Nicotinic and muscarinic cholinergic receptors coexist on GABAergic nerve endings in the mouse striatum and interact in modulating GABA release
2009, Neuropharmacology
Muscarinic cholinergic receptors (mAChRs) and nicotinic cholinergic receptors (nAChRs) regulating GABA release from striatal nerve endings were studied by monitoring release of previously accumulated [³H]GABA or endogenous GABA from superfused mouse striatal synaptosomes. Oxotremorine inhibited the release of [³H]GABA elicited by depolarization with 4-aminopyridine (4-AP), an effect antagonized by atropine. Agonists at nAChRs, including the α₄β₂^∗ subunit-selective RJR2403, provoked the release of [³H]GABA as well as of the endogenous transmitter; these effects also were prevented by oxotremorine and pilocarpine suggesting coexpression of functional mAChRs and α₄β₂^∗ nAChRs on GABAergic nerve endings. The inhibitory effects of oxotremorine on the release of [³H]GABA evoked by 4-AP or by RJR2403 were: (i) prevented by the M₂/M₄ mAChR antagonist himbacine; (ii) insensitive to the M2 antagonist AFDX116; (iii) blocked by the selective M₄ mAChR antagonists MT3, thus indicating the involvement of receptors of the M₄ subtype. In conclusion, in the corpus striatum, acetylcholine released from cholinergic interneurons can activate α₄β₂^∗ nAChRs mediating release of GABA; this evoked release can be negatively modulated by M₄ mAChRs coexpressed on the same GABAergic terminals.

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Muscarinic receptors mediate direct inhibition of GABA release from rat striatal nerve terminals

Abstract

Brain Res.

Neuropharmacology

Neuroscience

Neuroscience

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Neuroscience

Neurochem. Int.

Eur. J. Pharmacol.

GABA induced changes in acetylcholine release from slices of guinea-pig brain

Naunyn-Schmiedeberg's Arch. Pharmacol.

A type of aspiny neuron in the rat neostriatum accumulates [3H]gamma-aminobutyric acid: combination of Golgi-staining, autoradiography and electron microscopy

J. Comp. Neurol.

Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea

Nature

A type of aspiny neuron in the rat neostriatum accumulates [³H]gamma-aminobutyric acid: combination of Golgi-staining, autoradiography and electron microscopy