scholarly journals Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens

2015 ◽  
Vol 112 (26) ◽  
pp. 8124-8129 ◽  
Author(s):  
Jung Hoon Shin ◽  
Martín F. Adrover ◽  
Jürgen Wess ◽  
Veronica A. Alvarez
Keyword(s):  
Glutamate Release ◽  
Cholinergic Transmission ◽  
Ach Release ◽  
Axonal Projections ◽  
Midbrain Neurons ◽  
Glutamate Transmission ◽  
Neuron Terminals ◽  
Dependent Mechanism ◽  
Da Release ◽  
Ach Receptors

Cholinergic transmission in the striatum functions as a key modulator of dopamine (DA) transmission and synaptic plasticity, both of which are required for reward and motor learning. Acetylcholine (ACh) can elicit striatal DA release through activation of nicotinic ACh receptors (nAChRs) on DA axonal projections. However, it remains controversial how muscarinic ACh receptors (mAChRs) modulate striatal DA release, with studies reporting both potentiation and depression of striatal DA transmission by mAChR agonists. This study investigates the mAChR-mediated regulation of release from three types of midbrain neurons that project to striatum: DA, DA/glutamate, and glutamate neurons. We found that M5 mAChRs potentiate DA and glutamate release only from DA and DA/glutamate projections from the midbrain. We also show that M2/M4 mAChRs depress the nAChR-dependent mechanism of DA release in the striatum. These results suggest that M5 receptors on DA neuron terminals enhance DA release, whereas M2/M4 autoreceptors on cholinergic terminals inhibit ACh release and subsequent nAChR-dependent DA release. Our findings clarify the mechanisms of mAChR-dependent modulation of DA and glutamate transmission in the striatum.

scholarly journals Dopamine Release Neuroenergetics in Mouse Striatal Slices

2020 ◽  
Author(s):  
Msema Msackyi ◽  
Yuanxin Chen ◽  
Wangchen Tsering ◽  
Ninghan Wang ◽  
Jingyu Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nucleus Accumbens ◽  
Oxidative Phosphorylation ◽  
Neurodegenerative Disorder ◽  
Dorsal Striatum ◽  
Striatal Slices ◽  
Axonal Projections ◽  
Specific Vulnerability ◽  
Da Release

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disease. Dopamine (DA) neurons in the substantia nigra par compacta with axonal projections to the dorsal striatum (dSTR) degenerate in PD while in contrast, DA neurons in the ventral tegmental area with axonal projections to the ventral striatum including the nucleus accumbens (NAcc) shell, are largely spared. To understand the pathogenesis of PD, it is important to study the neuroenergetics of DA neurons. This study aims to uncover the relative contribution of glycolysis and oxidative phosphorylation (OxPhos) to evoked DA release in the striatum. We measured evoked DA release in mouse striatal brain slices by fast-scan cyclic voltammetry every 2 minutes. Blocking OxPhos caused a greater reduction in evoked DA release in the dSTR compared to the NAcc shell, and blocking glycolysis caused a greater reduction in evoked DA release in the NAcc shell than in the dSTR. Furthermore, when glycolysis was bypassed in favor of direct OxPhos, evoked DA release in the NAcc shell was decreased by ∼50% over 40 minutes whereas evoked DA release in the dSTR was largely unaffected. These results demonstrated that the dSTR relies primarily on OxPhos for energy production to maintain evoked DA release whereas the NAcc shell relies more on glycolysis. Using two-photon imaging, we consistently found that the oxidation level of the DA terminals was higher in the dSTR than in the NAcc shell. Together, these findings partially explain the specific vulnerability of DA terminals in the dSTR to degeneration in PD.Significant statementThe neuroenergetics of dopaminergic neuron is important to understand Parkinson’s disease (PD), a neurodegenerative disorder associated with mitochondrial dysfunctions. However, the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to presynaptic energy demands in DA terminals are unclear. We addressed this question by measuring DA release in the dorsal striatum and nucleus accumbens (NAcc) shell of mouse brain using FSCV under reagents blocking different energy systems. We found that the NAcc shell relies on both glycolysis and OxPhos to maintain DA release while the dSTR relies heavily on OxPhos. We demonstrate the different neuroenergetics of DA terminals in these two brain areas, providing new fundamentally important insight into the specific vulnerability of DA terminals in the dSTR to degeneration in PD.

scholarly journals Neurexins Regulate GABA Co-release by Dopamine Neurons

2021 ◽  
Author(s):  
Charles Ducrot ◽  
Gregory de Carvalho ◽  
Benoit Delignat-Lavaud ◽  
Constantin Delmas ◽  
Nicolas Giguere ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dopamine Neurons ◽  
Electrophysiological Recording ◽  
Conditional Deletion ◽  
Synaptic Cell Adhesion Molecules ◽  
Midbrain Dopamine ◽  
Neuron Terminals ◽  
Reduced Rate ◽  
Activity Dependent ◽  
Da Release

Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain of these neurons is highly complex, with a large subset of non-synaptic release sites and a smaller subset of synaptic terminals from which glutamate or GABA are released. The molecular mechanisms regulating the connectivity of DA neurons and their neurochemical identity are unknown. Here we tested the hypothesis that the trans-synaptic cell adhesion molecules neurexins (Nrxns) regulate DA neuron neurotransmission. Conditional deletion of all Nrxns in DA neurons (DAT::Nrxns KO) revealed that loss of Nrxns does not impair the basic development and ultrastructural characteristics of DA neuron terminals. However, loss of Nrxns caused an impairment of DA transmission revealed as a reduced rate of DA reuptake following activity-dependent DA release, decreased DA transporter levels, increased vesicular monoamine transporter expression and impaired amphetamine-induced locomotor activity. Strikingly, electrophysiological recording revealed an increase of GABA co-release from DA neuron axons in the striatum of the KO mice. These findings reveal that Nrxns act as key regulators of DA neuron connectivity and DA-mediated functions.

scholarly journals Isolation of Hydroxyoctaprenyl-1′,4′-hydroquinone, a new Octaprenylhydroquinone from the Marine Sponge Sarcotragus spinosulus and Evaluation of its Pharmacological Activity on Acetylcholine and Glutamate Release in the Rat Central Nervous System

2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Angela Bisio ◽  
Ernesto Fedele ◽  
Anna Pittaluga ◽  
Guendalina Olivero ◽  
Massimo Grilli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pharmacological Activity ◽  
Marine Sponge ◽  
Glutamate Release ◽  
Rat Hippocampus ◽  
Cholinergic Transmission ◽  
New Class ◽  
Mammalian Central Nervous System

Three polyprenyl-1′,4′-hydroquinone derivatives, heptaprenyl-1′,4′-hydroquinone (1), octaprenyl-1′,4′-hydroquinone (2), and hydroxyoctaprenyl-1′,4′-hydroquinone (3) were isolated from the marine sponge Sarcotragus spinosulus collected at Baia di Porto Conte, Alghero (Italy). Our findings indicate that the compounds isolated from S. spinosulus can significantly modulate the release of glutamate and acetylcholine in the rat hippocampus and cortex and might, therefore, represent the prototype of a new class of drugs regulating glutamatergic and cholinergic transmission in the mammalian central nervous system.

Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide

1990 ◽  
Vol 259 (6) ◽  
pp. G934-G939 ◽  
Author(s):  
M. W. Mulholland ◽  
S. Jaffer
Keyword(s):  
Myenteric Plexus ◽  
Acetylcholine Release ◽  
Calcitonin Gene Related Peptide ◽  
Ach Release ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Dependent Mechanism ◽  
Stimulation Of

The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.

scholarly journals Cholinergic suppression of visual responses in primate V1 is mediated by GABAergic inhibition

2012 ◽  
Vol 108 (7) ◽  
pp. 1907-1923 ◽  
Author(s):  
Anita A. Disney ◽  
Chiye Aoki ◽  
Michael J. Hawken
Keyword(s):  
Glutamate Release ◽  
Cell Types ◽  
Cholinergic Receptor ◽  
Receptor Subtypes ◽  
Specific Cell ◽  
Visual Responses ◽  
Ach Release ◽  
Anatomical Studies ◽  
Gain Enhancement ◽  
Tuning Width

Acetylcholine (ACh) has been implicated in selective attention. To understand the local circuit action of ACh, we iontophoresed cholinergic agonists into the primate primary visual cortex (V1) while presenting optimal visual stimuli. Consistent with our previous anatomical studies showing that GABAergic neurons in V1 express ACh receptors to a greater extent than do excitatory neurons, we observed suppressed visual responses in 36% of recorded neurons outside V1's primary thalamorecipient layer (4c). This suppression is blocked by the GABAA receptor antagonist gabazine. Within layer 4c, ACh release produces a response gain enhancement (Disney AA, Aoki C, Hawken MJ. Neuron 56: 701–713, 2007); elsewhere, ACh suppresses response gain by strengthening inhibition. Our finding contrasts with the observation that the dominant mechanism of suppression in the neocortex of rats is reduced glutamate release. We propose that in primates, distinct cholinergic receptor subtypes are recruited on specific cell types and in specific lamina to yield opposing modulatory effects that together increase neurons' responsiveness to optimal stimuli without changing tuning width.

Ventilatory output and acetylcholine: perturbations in release and muscarinic receptor activation

1994 ◽  
Vol 77 (5) ◽  
pp. 2275-2284 ◽  
Author(s):  
M. D. Burton ◽  
K. Nouri ◽  
S. Baichoo ◽  
N. Samuels-Toyloy ◽  
H. Kazemi
Keyword(s):  
Muscarinic Receptors ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Dependent Manner ◽  
Cholinergic Transmission ◽  
Ach Release ◽  
Tetraethylammonium Chloride ◽  
Spinal Axis ◽  
Dose Dependent ◽  
Stimulation Of

Cholinergic transmission may be part of the normal neurochemical processes that support spontaneous ventilation. If this is true, perturbations in acetylcholine (ACh) turnover should alter ventilatory output in a predictable manner. With the use of the isolated perfused brain stem-spinal axis from the neonatal rat, the effects of modifiers of ACh release and blockers of muscarinic receptors on spontaneous C4 (phrenic) output were determined. Vesamicol and cetiedil, inhibitors of ACh release, caused depression and cessation of the C4 output in a dose-dependent manner when added to the perfusate. Muscarinic blockers, particularly M1 and M3 blockers, caused a similar depression. 4-Aminopyridine and tetraethylammonium chloride, facilitators of ACh release, caused stimulation of C4 (phrenic) output. The depressive effects of the blockers and inhibitors were reversible with facilitation of ACh release except in the case of cetiedil. These findings are consistent with the view that the synaptic turnover of endogenous ACh is an important part of the normal neurochemical process that supports and modulates ventilation.

scholarly journals Kainate receptors regulate development of glutamatergic synaptic circuitry in the rodent amygdala

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Maria Ryazantseva ◽  
Jonas Englund ◽  
Alexandra Shintyapina ◽  
Johanna Huupponen ◽  
Vasilii Shteinikov ◽  
...  
Keyword(s):  
Information Processing ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Physiological Mechanism ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Development ◽  
Synaptic Circuitry ◽  
Amygdaloid Nuclei ◽  
Dependent Mechanism

Perturbed information processing in the amygdala has been implicated in developmentally originating neuropsychiatric disorders. However, little is known on the mechanisms that guide formation and refinement of intrinsic connections between amygdaloid nuclei. We demonstrate that in rodents the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first 10 postnatal days, before external inputs underlying amygdala-dependent behaviors emerge. During this restricted period of synaptic development, kainate-type of ionotropic glutamate receptors (KARs) are highly expressed in the BLA and tonically activated to regulate glutamate release via a G-protein-dependent mechanism. Genetic manipulation of this endogenous KAR activity locally in the newborn LA perturbed development of glutamatergic input to CeA, identifying KARs as a physiological mechanism regulating formation of the glutamatergic circuitry in the amygdala.

scholarly journals Kainate-type of glutamate receptors regulate wiring of intrinsic glutamatergic connectivity in the amygdala

2019 ◽  
Author(s):  
Maria Ryazantseva ◽  
Jonas Englund ◽  
Alexandra Shintyapina ◽  
Johanna Huupponen ◽  
Asla Pitkänen ◽  
...  
Keyword(s):  
Information Processing ◽  
Glutamate Receptors ◽  
G Protein ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Physiological Mechanism ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Development ◽  
Amygdaloid Nuclei ◽  
Dependent Mechanism

SummaryPerturbed information processing in the amygdala has been implicated in developmentally originating neuropsychiatric disorders. However, little is known on the mechanisms that guide formation and refinement of intrinsic connections between amygdaloid nuclei. We demonstrate that the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first ten postnatal days, before external inputs underlying amygdala dependent behaviors emerge. During this restricted period of synaptic development, kainate-type of ionotropic glutamate receptors (KARs) are highly expressed in the BLA and tonically activated to regulate glutamate release via a G-protein dependent mechanism. Genetic manipulation of this endogenous KAR activity locally in the newborn LA perturbed development of glutamatergic input to CeA, identifying KARs as a physiological mechanism regulating wiring of the intrinsic glutamatergic circuitry in the amygdala.

scholarly journals Muscarinic and Nicotinic Modulation of Neocortical Layer 6A Synaptic Microcircuits Is Cooperative and Cell-Specific

2019 ◽  
Vol 30 (6) ◽  
pp. 3528-3542 ◽  
Author(s):  
Danqing Yang ◽  
Robert Günter ◽  
Guanxiao Qi ◽  
Gabriele Radnikow ◽  
Dirk Feldmeyer
Keyword(s):  
Differential Expression ◽  
Somatosensory Cortex ◽  
Pyramidal Cell ◽  
Glutamate Release ◽  
Synaptic Connections ◽  
Presynaptic Neuron ◽  
Synaptic Release ◽  
Low Concentrations ◽  
Behavioral States ◽  
Ach Receptors

Abstract Acetylcholine (ACh) is known to regulate cortical activity during different behavioral states, for example, wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic ACh receptors (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M 4 and M1 mAChRs, respectively. At ~ 1 mM, ACh depolarized exclusively CT PCs via α4β2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via α4β2 nAChRs when the presynaptic neuron was a CT PC. Thus, in L6A, the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening CT output while weakening CC synaptic signaling.

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