scholarly journals Differential Muscarinic Modulation of Synaptic Transmission in Dorsal and Ventral Regions of the Rat Nucleus Accumbens Core

2014 ◽  
pp. 135-142
Author(s):  
X. JIANG ◽  
J. J. ZHANG ◽  
M. Y. WANG ◽  
N. SUI
Keyword(s):  
Nucleus Accumbens ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Nucleus Accumbens Core ◽  
Concentration Dependent Manner ◽  
Paired Pulse ◽  
Presynaptic Mechanisms

The nucleus accumbens (NAc) core is critical in the control of motivated behaviors. The muscarinic acetylcholine receptors (mAChRs) modulating the excitatory inputs into the NAc core have been reported to impact such behaviors. Recent studies suggest that ventral and dorsal regions of the NAc core seem to be innervated by distinct populations of glutamatergic projection neurons. To further examine mAChRs modulation of these glutamatergic inputs to the NAc core, we employed intracellular recordings in rat NAc coronal slice preparation to characterize: 1) the effects of muscarine, an mAChRs agonist, on membrane properties of the NAc core neurons; 2) depolarizing synaptic potentials (DPSP) elicited by ventral and dorsal focal electrical stimuli; and 3) paired-pulse response with paired-pulse stimulation. Here we report that the paired-pulse ratio (PPR) elicited by dorsal stimuli was greater than that elicited by ventral stimuli. Bath application of muscarine (1-30 μM) decreased both ventral and dorsal DPSP in a concentration-dependent manner, with no effect on electrophysiological properties of NAc core neurons. Muscarine at 30 μM also elicited larger depression of dorsal DPSP than ventral DPSP. Moreover, muscarine increased the PPR of both dorsal and ventral DPSP. These data indicate that the glutamatergic afferent fibers traversing the dorsal and ventral NAc are separate, and that differential decrease of distinct afferent excitatory neurotransmission onto NAc core neurons may be mediated by presynaptic mechanisms.

Riluzole Anesthesia

1996 ◽  
Vol 85 (3) ◽  
pp. 626-634. ◽  
Author(s):  
M. Bruce MacIver ◽  
Shanti M. Amagasu ◽  
Anthony A. Mikulec ◽  
Frances A. Monroe
Keyword(s):  
Butyric Acid ◽  
Brain Slices ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Gamma Amino Butyric Acid ◽  
General Anesthetic ◽  
Output Analysis ◽  
Concentration Dependent Manner ◽  
Paired Pulse ◽  
Amino Butyric Acid

Background Riluzole (RP 54274) is an experimental benzothiazole with anesthetic properties, but little is known about its synaptic or cellular actions. Methods The authors investigated riluzole effects on synaptic response of CA 1 pyramidal neurons in rat hippocampal brain slices. Electrophysiologic recordings of population spikes (PS), excitatory postsynaptic potentials (EPSP), and fiber volleys were studied. Paired pulse stimulation (120 ms interpulse interval) was used to measure effects on gamma-amino butyric acid (GABA)-mediated synaptic inhibition, and stimulus trains (33 Hz) were used to test for use-dependent effects. Results Synaptically evoked PS discharge was blocked in a concentration-dependent manner by riluzole (2.0-20 microM), similar to effects produced by other anesthetics. Paired pulse inhibition was not altered by riluzole. In contrast, 20 microM thiopental produced a marked increase in paired pulse inhibition. Riluzole (5.0 microM) produced a 46.6 +/- 19.8% depression of glutamate-mediated EPSPs, which could account for most of the mate-mediated EPSPs, which could account for most of the depression of PS discharge (54.2 +/- 12.6%) produced by this concentration. Riluzole produced a 36 +/- 17% depression of fiver volley amplitudes, which, based on input/output analysis, could completely account for the depression of EPSPs. The depression of fiber volley amplitudes showed a marked use-dependence; the second and subsequent action potentials in a train were progressively depressed by riluzole to a greater extent than the first action potential. Conclusions Riluzole produced a potent block of excitatory synaptic transmission via depression of presynaptic conduction in glutamatergic nerve fibers. The use-dependent depression observed resembled that produced by some local anesthetics on nerve conduction and sodium channels. The presynaptic action, together with a lack of effect on gamma-amino butyric acid-mediated inhibition, provides a unique mechanism of action for a general anesthetic.

scholarly journals Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior

2019 ◽  
Author(s):  
Anne L. Collins ◽  
Tara J. Aitken ◽  
I-Wen Huang ◽  
Christine Shieh ◽  
Venuz Y. Greenfield ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Female Rats ◽  
Nucleus Accumbens Core ◽  
Cholinergic Interneurons ◽  
Reward Seeking ◽  
Motivated Behavior ◽  
Male And Female Rats ◽  
Seeking Behavior

ABSTRACTBackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.MethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.ResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of β2-containing nicotinic acetylcholine receptors.ConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.

scholarly journals Loss of muscarinic M5 receptor function manifests disparate impairments in exploratory behavior in male and female mice despite common dopamine regulation

2021 ◽  
Author(s):  
John A Razidlo ◽  
Skylar ML Fausner ◽  
Liuchang C Wang ◽  
Salahudeen A Mirza ◽  
Veronica A Alvarez ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Therapeutic Target ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Dopamine Neurons ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Attractive Therapeutic Target ◽  
Dopamine Transmission

There are five cloned muscarinic acetylcholine receptors (M1-M5). Of these, the muscarinic type 5 receptor (M5) is the only one localized to dopamine neurons in the ventral tegmental area and substantia nigra. Unlike M1-M4, the M5 receptor has relatively restricted expression in the brain, making it an attractive therapeutic target. Here we performed an in-depth characterization of M5-dependent potentiation of dopamine transmission in the nucleus accumbens and accompanying exploratory behaviors in male and female mice. We show that M5 receptors potentiate dopamine transmission by acting directly on the terminals within the nucleus accumbens. Using the agonist oxotremorine, we revealed a unique concentration response curve and a sensitivity to repeated stressor exposure. We found that constitutive deletion of M5 receptors reduced exploration of the center of an open field while at the same time impairing normal habituation only in male mice. In addition, M5 deletion reduced exploration of salient stimuli, especially under conditions of high novelty, yet had no effect on hedonia. We conclude that M5 receptors are critical for both engaging with the environment and updating behavioral output in responses to the environment cues, specifically in male mice. A cardinal feature of mood and anxiety disorders is a withdrawal from the environment. These data indicate that boosting M5 receptor activity may be a useful therapeutic target for ameliorating these symptoms of depression and anxiety.

scholarly journals Spinal cholinergic interneurons differentially control motoneuron excitability and alter the locomotor network operational range

2017 ◽  
Author(s):  
Maria Bertuzzi ◽  
Konstantinos Ampatzis
Keyword(s):  
Acetylcholine Receptors ◽  
Neuronal Firing ◽  
Muscarinic Acetylcholine Receptors ◽  
Dependent Manner ◽  
Functional Flexibility ◽  
Cholinergic Interneurons ◽  
Neuronal Mechanisms ◽  
Intrinsic Plasticity ◽  
Unexpected Findings ◽  
Operational Range

SummaryWhile cholinergic neuromodulation is important for locomotor circuit operation, the specific neuronal mechanisms that acetylcholine employs to regulate and fine-tune the speed of locomotion are largely unknown. Here, we show that cholinergic interneurons are present in the zebrafish spinal cord and differentially control the excitability of distinct classes of motoneurons (slow, intermediate and fast) in a muscarinic dependent manner. Moreover, we reveal that m2-type muscarinic acetylcholine receptors (mAChRs) are present in fast and intermediate motoneurons, but not in the slow motoneurons, and that their activation decreases neuronal firing. We also provide evidence that this configuration of motoneuron muscarinic receptors serves as the main intrinsic plasticity mechanism to alter the operational range of motoneuron modules. These unexpected findings provide new insights into the functional flexibility of motoneurons and how they execute locomotion at different speeds.

scholarly journals Role of Muscarinic Acetylcholine Receptors in Breast Cancer: Design of Metronomic Chemotherapy

2019 ◽  
Vol 14 (2) ◽  
pp. 91-100 ◽  
Author(s):  
María E. Sales ◽  
Alejandro J. Español ◽  
Agustina R. Salem ◽  
Paola M. Pulido ◽  
Y. Sanchez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Acetylcholine Receptors ◽  
Metronomic Chemotherapy ◽  
Chemotherapeutic Agents ◽  
Muscarinic Acetylcholine Receptors ◽  
Therapeutic Interventions ◽  
Dependent Manner ◽  
Muscarinic Agonists ◽  
Muscarinic Acetylcholine

Background: muscarinic acetylcholine receptors (mAChRs) have attracted interest as targets for therapeutic interventions in different illnesses like Alzheimer´s disease, viral infections and different tumors. Regarding the latter, many authors have studied each subtype of mAChRs, which seem to be involved in the progression of distinct types of malignancies. Methods: We carefully revised research literature focused on mAChRs expression and signaling as well as in their involvement in cancer progression and treatment. The characteristics of screened papers were described using the mentioned conceptual framework. Results: Muscarinic antagonists and agonists have been assayed for the treatment of tumors established in lung, brain and breast with beneficial effects. We described an up-regulation of mAChRs in mammary tumors and the lack of expression in non-tumorigenic breast cells and normal mammary tissues. We and others demonstrated that muscarinic agonists can trigger anti-tumor actions in a dose-dependent manner on tumors originated in different organs like brain or breast. At pharmacological concentrations, they exert similar effects to traditional chemotherapeutic agents. Metronomic chemotherapy refers to the administration of anti-cancer drugs at low doses with short intervals among them, and it is a different regimen applied in cancer treatment reducing malignant growth and angiogenesis, and very low incidence of adverse effects. Conclusion: The usage of subthreshold concentrations of muscarinic agonists combined with conventional chemotherapeutic agents could be a promising tool for breast cancer therapy.

Inhibitory Effects of Isoflurane and Nonimmobilizing Halogenated Compounds on Neuronal Nicotinic Acetylcholine Receptors

2002 ◽  
Vol 97 (6) ◽  
pp. 1541-1549 ◽  
Author(s):  
Takayuki Matsuura ◽  
Yoshinori Kamiya ◽  
Hideki Itoh ◽  
Tomoko Higashi ◽  
Yoshitsugu Yamada ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Volatile Anesthetics ◽  
Dependent Manner ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Halogenated Compounds ◽  
Concentration Dependent Manner ◽  
Amnesic Effect ◽  
Nicotinic Acetylcholine

Background Neuronal nicotinic acetylcholine receptors (nAchRs) are inhibited by low concentrations of volatile anesthetics. However, it is not clear whether this phenomenon contributes to the anesthetic effects of volatile anesthetics. Effects of a volatile anesthetic (isoflurane) and structurally related nonimmobilizers (F6: 1,2-dichlorohexafluorocyclobutane, F8: 2,3-dichlorooctafluorobutane) on the current mediated through neuronal nAchRs were studied. Method This study investigated neuronal nAchRs in PC12 cells and acutely dissociated rat medial habenula (MHb) neurons. Whole cell currents elicited by 30 microm nicotine were recorded in the absence and presence of the halogenated agents. The minimum alveolar concentrations (MACs) for F6 and F8 were predicted from Meyer-Overton correlation. Results All halogenated compounds inhibited the nicotine-induced current in a concentration-dependent manner in PC12 cells. In MHb neurons, while isoflurane and F6 significantly inhibited the nicotine-induced peak current, F8 failed to inhibit it. The peak currents in the presence of isoflurane at 1.7 MAC, of F6 at 2.4 MAC, and of F8 at 2.2 MAC were 12, 31, and 97% of control, respectively. Conclusions Isoflurane, F6, and F8 inhibited ganglion-type nAchRs in PC12 cells independent from their abilities to produce the anesthetic state. In MHb neurons, isoflurane and F6, which lack the immobilizing effect but has the amnesic effect, inhibited nAchRs. Native brain nicotinic receptors in MHb neurons were almost insensitive to F8, which lacks both the immobilizing and the amnesic effect. These results are consistent with the hypothesis that inhibition of nAchRs in MHb neurons is not important for the anesthetic effect but may contribute to the amnesic effect of these agents.

Actions of nitric oxide-generating sodium nitroprusside in myenteric plexus of guinea pig small intestine

1993 ◽  
Vol 265 (5) ◽  
pp. G887-G893 ◽  
Author(s):  
K. Tamura ◽  
M. Schemann ◽  
J. D. Wood
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Guinea Pig ◽  
Sodium Nitroprusside ◽  
Myenteric Plexus ◽  
Membrane Properties ◽  
Dependent Manner ◽  
Membrane Excitability ◽  
Concentration Dependent Manner ◽  
Myenteric Neurons

Sodium nitroprusside (NaNP) was used as a donor of nitric oxide (NO) to investigate actions of NO on electrical and synaptic behavior of single myenteric neurons in guinea pig small intestine. NaNP (10 microM-1 mM) did not affect resting membrane properties of the neurons, except for an occasional decrease in input resistance and hyperpolarization attributable to suppression of excitatory transmitter release. NaNP did not alter fast nicotinic neurotransmission but suppressed noncholinergic slow excitatory postsynaptic potentials (slow EPSPs) in a concentration-dependent manner. Pretreatment with either methylene blue or oxyhemoglobin reduced the inhibitory action of NaNP on the slow EPSPs. Slow EPSP-like responses to microejected substance P or 5-hydroxytryptamine were unaffected by NaNP. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, did not affect resting membrane excitability or excitatory synaptic events in any of the myenteric neurons. The results suggest that NO may not be released extensively as a neurotransmitter at synapses within the myenteric plexus. If myenteric neurons are exposed to NO released from nonneural sources, then the principal action is expected to be presynaptic inhibition of slow synaptic excitation.

Sign in / Sign up

Export Citation Format

Share Document