Wu M, Xu C, Alreja M (2002) Physiological and pharmacological characteristics of the inhibitory muscarinic response in septohippocampal cholinergic neurons. Neuroscience 2002 Abstracts 35.7. Society for Neuroscience, Orlando, FL.
Summary: Septohippocampal cholinergic neurons in the MSDB provide the hippocampus with almost its entire ACh and also release ACh locally within the MSDB. The released ACh sustains activity in the GABAergic limb of the septohippocampal pathway. Septohippocampal cholinergic neurons undergo atrophy in neurodegenerative disorders associated with loss of cognition. In a recent study we demonstrated that 65% of septohippocampal cholinergic neurons are inhibited by ACh via muscarinic receptors. Because of the importance of ACh and septohippocampal cholinergic neurons in cognition, we studied the physiological and pharmacological properties of the muscarinic response in MSDB neurons. Using intracellular and whole-cell recordings, we tested the effects of muscarine on retrogradely-labeled septohippocampal cholinergic neurons in vitro in rat brain slices. The cells were labeled using the Cy3-192IgG, a selective marker of septohippocampal cholinergic neurons. Prolonged (10-15 mins) but not short (1-2 min) applications of muscarine or oxotremorine produced a marked desensitization (>50%). The muscarine-induced outward current was found to be mediated via direct as well as indirect mechanisms. It reversed at Ek and was blocked by external barium. The M2/M4 antagonist, methoctramine blocked the muscarine response in only 10% of the neurons tested and tropicamide, an M4-prefering antagonist, blocked the muscarine response in 5/5 neurons tested, suggesting possible involvement of M4 receptors.
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