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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
Published on: October 29, 2012
Cholinergic interneurons control local circuit activity and cocaine conditioning.
Ilana B Witten1, Shih-Chun Lin, Matthew Brodsky
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|December 18, 2010
Summary
Cholinergic interneurons in the nucleus accumbens, though rare, powerfully control brain circuits. Silencing these neurons blocked cocaine conditioning, revealing their critical role in drug addiction.
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Cholinergic neurons are widespread, impacting many brain processes.
- Lack of specificity in pharmacological modulation limits understanding of cholinergic neuron roles.
- Causal roles of cholinergic neurons in neural circuits remain unclear.
Purpose of the Study:
- To investigate the function of cholinergic interneurons in the nucleus accumbens.
- To determine the specific control these neurons exert over neural circuits.
- To explore the involvement of these neurons in cocaine addiction.
Main Methods:
- Optogenetics for direct excitation/inhibition of nucleus accumbens cholinergic interneurons.
- In vivo and slice electrophysiology to record neural activity.
- Freely moving mammalian behavioral paradigms, including cocaine conditioning.
Main Results:
- Cholinergic interneurons, despite being <1% of local neurons, exert dominant control over nucleus accumbens circuit activity.
- These neurons are activated by cocaine.
- Silencing cocaine-induced cholinergic interneuron activity blocked cocaine conditioning.
Conclusions:
- Nucleus accumbens cholinergic interneurons play a critical role in modulating neural circuits.
- These neurons are essential for the development of cocaine addiction.
- Targeting these specific neurons may offer novel therapeutic strategies for addiction.
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