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Related Concept Videos

Cholinergic Receptors: Muscarinic01:25

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The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
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Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
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Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
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Cholinergic Neurons: Neurotransmission01:23

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Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
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Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

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Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
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Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
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Molecularly defined and functionally distinct cholinergic subnetworks.

Xinyan Li1, Hongyan Yu2, Bing Zhang2

  • 1Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 4030030, China; Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China.

Neuron
|September 21, 2022
PubMed
Summary
This summary is machine-generated.

Researchers discovered two distinct types of cholinergic neurons in the medial septum (MS) that differ in gene expression and connectivity. These neuron subsets play separate roles in regulating anxiety and spatial memory.

Keywords:
anxiety-like behaviorscalbindin D28Kcholinergic neuronshippocampusmedial septumspatial memory

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Behavioral Science

Background:

  • Cholinergic neurons in the medial septum (MS) are crucial for forebrain functions like memory and attention.
  • Previous research has largely overlooked the diversity within MS cholinergic neuron populations, hindering understanding of their functional roles.

Purpose of the Study:

  • To investigate the organizational principles and functional diversity of MS cholinergic neurons.
  • To identify distinct subpopulations of MS cholinergic neurons and their specific roles in behavior.

Main Methods:

  • Topographical mapping and genetic marker analysis to identify distinct cholinergic neuron subsets (D28K+ vs. D28K-).
  • Electrophysiological recordings to characterize neuronal signatures.
  • Molecular analysis of marker gene expression (kcnh1, aifm3, cacna1h, gga3).
  • Circuit tracing and functional studies (gain- and loss-of-function) in the hippocampus.

Main Results:

  • Identified two topographically segregated cholinergic neuron subsets (D28K+ and D28K-) in mice, macaques, and humans.
  • These subsets exhibit unique electrophysiological properties and express mutually exclusive gene markers.
  • Demonstrated differential connectivity with hippocampal neuronal classes, forming distinct circuits.
  • Showed that these circuits differentially modulate anxiety-like behavior and spatial memory.

Conclusions:

  • MS cholinergic neurons comprise functionally distinct subpopulations with unique molecular and circuitry underpinnings.
  • These findings provide a framework for understanding how cholinergic system diversity contributes to complex cognitive and emotional functions.
  • Highlights the importance of considering neuronal heterogeneity for a comprehensive understanding of brain function.