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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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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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Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
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Related Experiment Video

Updated: Sep 4, 2025

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry CIS-FSCV to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine
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Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry CIS-FSCV to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

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Dopamine D2Rs coordinate cue-evoked changes in striatal acetylcholine levels.

Kelly M Martyniuk1,2, Arturo Torres-Herraez2,3, Daniel C Lowes2,3

  • 1Department of Neuroscience, Columbia University, New York, United States.

Elife
|July 20, 2022
PubMed
Summary
This summary is machine-generated.

Dopamine D2 receptors on cholinergic interneurons do not initiate the cholinergic pause but prolong it, impacting action motivation. This research explores dopamine and acetylcholine (ACh) interactions in natural behaviors.

Keywords:
acetylcholinecircuitdopaminemotivationmouseneuromodulationneurosciencestriatum

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Area of Science:

  • Neuroscience
  • Neurobiology
  • Behavioral Neuroscience

Background:

  • Acetylcholine (ACh) and dopamine (DA) signaling in the striatum are crucial for reward processing and motivated behavior.
  • The precise in vivo regulation of ACh by DA, particularly during natural behaviors, remains incompletely understood.
  • A key debate concerns whether DA induces or modulates the cue-evoked cholinergic pause via D2 receptors (D2Rs).

Purpose of the Study:

  • To investigate the role of D2Rs on striatal cholinergic interneurons (CINs) in regulating ACh and DA dynamics during cue-evoked behaviors.
  • To determine if CIN D2Rs are necessary for initiating the cholinergic pause or modulate its duration and recovery.
  • To elucidate the contribution of ACh signaling, modulated by D2Rs, to action initiation and motivation.

Main Methods:

  • Simultaneous measurement of ACh and DA levels using genetically encoded sensors in mice.
  • Pharmacological and genetic inactivation of D2Rs specifically in CINs.
  • Behavioral analysis of cue-elicited action initiation (lever pressing) and correlation with neurochemical signals.

Main Results:

  • CIN D2R inactivation did not affect the initiation of cue-induced ACh decrease but prolonged its duration and inhibited ACh rebound.
  • Cue-evoked DA release remained unaltered by CIN D2R inactivation.
  • D2R inactivation significantly reduced the temporal correlation between DA and ACh signals, both during cue presentation and intertrial intervals.
  • Behaviorally, D2R antagonism increased lever press latency, which correlated with the duration of the cue-evoked ACh decrease.

Conclusions:

  • CIN D2Rs are not essential for initiating the cue-evoked cholinergic pause but play a critical role in its temporal dynamics and subsequent recovery.
  • D2Rs on CINs coordinate DA and ACh signaling, suggesting a broader role in regulating striatal circuit activity.
  • The modulation of ACh signaling by D2Rs is implicated in the motivation to initiate actions, highlighting the importance of this interaction in behavioral control.