Localization of M2 muscarinic acetylcholine receptor protein in cholinergic and non-cholinergic terminals in rat hippocampus

Rouse, Susan T.; Edmunds, Sharon M.; Yi, Hong; Gilmor, Michelle L.; Levey, Aĺlan I.

doi:10.1016/s0304-3940(00)01011-9

Cited by 79 publications

(61 citation statements)

References 13 publications

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“…2,29 Presynaptic localization of M2 and M4 receptors in the hippocampus shows complementary patterns among the commissural/associational, perforant and septohippocampal pathways, and applies to both cholinergic and noncholinergic terminals. 8,29,30 Furthermore, because of the lack of subtype-specific ligands, contradictory results have been reported regarding the role of specific muscarinic receptor subtypes in regulating hippocampal cholinergic neurotransmission. For example, inhibitory muscarinic autoreceptors in the hippocampus have been classified as M2, M4, or as a mixture of M1 and M4 receptors 25,31,32 (reviewed by Vizi and Kiss 33 ).…”

Section: Discussionmentioning

confidence: 99%

Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice

et al. 2003

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Among the five different muscarinic receptors that have been cloned and characterized, M2 and M4 receptors are localized both post-and presynaptically and are believed to have a pronounced autoreceptor role. The functional importance of these receptors in the regulation of acetylcholine release in the hippocampus and in cognitive processes was investigated by using M2 and M4 receptor single knockout (KO) as well as M2/M4 receptor double KO mice. We found profound alterations in acetylcholine homeostasis in the hippocampus of both M2-and M4-KO mice as well as of the combined M2/M4-KOs, as assessed by in vivo microdialysis. Basal acetylcholine efflux in the hippocampus was significantly increased in M4-KO and was elevated further in M2/M4-KOs. The increase in hippocampal acetylcholine induced by local administration of scopolamine was markedly reduced in M2-KO and completely abolished in M2/M4-KOs. In M2-KO and much more in M2/M4-KOs, the increase in hippocampal acetylcholine triggered by exposure to a novel environment was more pronounced both in amplitude and duration, with a similar trend observed for M4-KOs. Dysregulation of cholinergic function in the hippocampus, as it could result from perturbed autoreceptor function, may be associated with cognitive deficits. Importantly, M2-and M2/M4-KO, but not M4-KO, animals showed an impaired performance in the passive avoidance test. Together these results suggest a crucial role for muscarinic M2 and M4 receptors in the tonic and phasic regulation of acetylcholine efflux in the hippocampus as well as in cognitive processes.

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Section: Discussionmentioning

confidence: 99%

Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice

et al. 2003

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“…The vast majority of M 2 receptors in the hippocampus reside as heteroreceptors on GABAergic terminals (Rouse et al, 2000). Some of these terminals arise either from septal GABA-containing afferents or intrinsic "disinhibitory" GABAergic cells, both of which impinge on other "inhibitory" interneurons (Freund and Antal, 1988;Gulyas et al, 1996;Hajos et al, 1998), which in turn exert powerful inhibitory control over large numbers of principal cells.…”

Section: Discussionmentioning

confidence: 99%

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

et al. 2002

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Hippocampal-dependent learning and memory deficits have been well documented in aging rodents. The results of several recent studies have suggested that these deficits arise from weakened synaptic plasticity within the hippocampus. In the present study, we examined the relationship between hippocampal long-term potentiation (LTP) in vitro and spatial learning in aged (24-26 months) Fischer 344 rats. We found that LTP induced in the CA1 region using theta-frequency stimulation (5 Hz) is selectively impaired in slices from a subpopulation of aged rats that had shown poor spatial learning in the Morris water maze. LTP at 5 Hz in aged rats that did not show learning deficits was similar to that seen in young (4-6 months) controls. We also found that 5 Hz LTP amplitude strongly correlated with individual learning performance among aged rats. The difference in 5 Hz LTP magnitude among aged rats was not attributable to an altered response to 5 Hz stimulation or to differences in the NMDA receptormediated field EPSP. In addition, no performance-related differences in LTP were seen when LTP was induced with 30 or 70 Hz stimulation protocols. Finally, both 5 Hz LTP and spatial learning in learning-impaired rats were enhanced with the selective muscarinic M 2 antagonist ]benzodiazepin-6-one). These findings reinforce the idea that distinct types of hippocampal LTP offer mechanistic insight into age-associated cognitive decline.

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“…In the hippocampus, M 2 , a G i/o -coupled mAChR, is expressed in cholinergic axons arising from the medial septum and diagonal band of Broca and also in GABAergic axons of parvalbumin-containing interneurons (196,445,446). M 2 and CB 1 are thus expressed in axons of distinct basket cells (168,263).…”

Section: Muscarinic Acetylcholine Receptorsmentioning

confidence: 99%

Endocannabinoid-Mediated Control of Synaptic Transmission

Kano¹,

Ohno‐Shosaku²,

Hashimotodani³

et al. 2009

Physiological Reviews

1,311

1,431

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The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

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Localization of M2 muscarinic acetylcholine receptor protein in cholinergic and non-cholinergic terminals in rat hippocampus

Cited by 79 publications

References 13 publications

Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice

Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

Endocannabinoid-Mediated Control of Synaptic Transmission

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