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Related Experiment Video

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Acetylcholine Engages Distinct Amygdala Microcircuits to Gate Internal Theta Rhythm.

Joshua X Bratsch-Prince1, James W Warren1, Grace C Jones1

  • 1Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina 29208.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|March 4, 2024
PubMed
Summary

Acetylcholine (ACh) triggers theta oscillations in the basolateral amygdala (BLA) via cholecystokinin interneurons, facilitating emotional memory. This mechanism reveals how salient stimuli enhance brain states for memory formation.

Keywords:
acetylcholineamygdalaemotioninterneuronoscillationtheta

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Area of Science:

  • Neuroscience
  • Neurophysiology
  • Molecular Biology

Background:

  • Acetylcholine (ACh) from basal forebrain neurons modulates attention and memory by inducing brain states associated with theta oscillations.
  • Theta oscillations in the basolateral amygdala (BLA) are linked to emotional memory, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the cellular and circuit mechanisms by which acetylcholine (ACh) induces theta oscillations in the basolateral amygdala (BLA).
  • To investigate the role of specific interneuron populations and muscarinic receptors in generating ACh-induced BLA theta oscillations.

Main Methods:

  • In vitro brain slice electrophysiology in male and female mice.
  • Stimulation with acetylcholine (ACh) and assessment of local field potentials in the BLA.
  • Pharmacological manipulation targeting M3 muscarinic receptors and specific interneuron populations (CCK, SOM, PV).

Main Results:

  • Large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials.
  • ACh-induced theta requires M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons, independent of external glutamate.
  • A functional circuit involving somatostatin (SOM) interneurons inhibiting CCK interneurons gates BLA theta, with ACh inhibiting SOM INs.
  • Parvalbumin (PV) interneurons, involved in baseline oscillations, are not required for ACh-induced theta, indicating a cellular switch.
  • Theta activity is more readily evoked in the BLA compared to the cortex or hippocampus.

Conclusions:

  • Acetylcholine (ACh) induces a cellular switch in the BLA, establishing internally driven theta oscillations through CCK interneurons.
  • A SOM→CCK interneuron circuit gates these ACh-induced theta oscillations in the BLA.
  • This mechanism suggests how salient stimuli, via ACh, shift the BLA into a network state conducive to emotional memory formation.