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Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex
Caitlin E Askew1, Alberto J Lopez1, Marcelo A Wood1
1Department of Neurobiology and Behavior, Center for Hearing Research, University of California, Irvine, Irvine, California.
Synapse (New York, N.Y.)
|May 14, 2019
Summary
Nicotine enhances sensory processing by exciting VIP neurons in the auditory cortex. This leads to disinhibition of pyramidal neurons, improving cognitive and sensory functions.
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Nicotine improves cognitive and sensory functions by activating nicotinic acetylcholine receptors in the cortex.
- Nicotine amplifies stimulus-evoked responses in sensory cortex, but specific cell types and circuits involved are unclear.
Purpose of the Study:
- To investigate the role of specific neuronal cell types and circuits in the nicotinic modulation of the mouse auditory cortex.
- To elucidate the cellular and synaptic mechanisms underlying nicotine's effects on sensory processing.
Main Methods:
- Whole-cell recordings from pyramidal (Pyr) neurons and inhibitory interneurons (PV, SOM, VIP) in mouse auditory cortex.
- Application of nicotine and receptor antagonists.
- Chemogenetic manipulation using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs).
Main Results:
- Nicotine strongly depolarized and excited VIP neurons, weakly depolarized Pyr neurons, and had no effect on SOM or PV neurons.
- Nicotine enhanced spontaneous inhibitory postsynaptic currents (sIPSCs) in Pyr, VIP, and SOM neurons, but not PV neurons.
- Inhibition of VIP neurons prevented nicotine's effects on Pyr neurons, suggesting VIP cells mediate nicotinic modulation.
Conclusions:
- Nicotine excites VIP neurons, which in turn disinhibit Pyr neurons, potentially enhancing auditory stimulus response.
- VIP cells also directly inhibit Pyr neurons, influencing synaptic input integration.
- These mechanisms contribute to nicotine's beneficial effects on cognitive and sensory function.
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