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Selective optogenetic stimulation of cholinergic axons in neocortex
Abigail Kalmbach1, Tristan Hedrick, Jack Waters
1Department of Physiology, Feinberg School of Medicine, Northwestern Univ., Chicago, IL 60611, USA.
Journal of Neurophysiology
|January 13, 2012
Summary
Researchers developed a novel method to selectively stimulate acetylcholine (ACh) release in the neocortex. This technique uses optogenetics to target cholinergic neurons, overcoming limitations of previous non-selective stimulation methods.
Area of Science:
- Neuroscience
- Neurophysiology
- Optogenetics
Background:
- Acetylcholine (ACh) plays a critical role in neocortical functions including arousal, attention, and memory.
- Cholinergic projections to the neocortex originate mainly from the nucleus basalis, which also releases other neurotransmitters.
- Non-selective stimulation methods have hindered research into the specific functions of ACh in the neocortex.
Purpose of the Study:
- To develop a method for the selective stimulation of cholinergic axons in the neocortex.
- To enable precise investigation of acetylcholine's role in neocortical function.
Main Methods:
- Utilized the Cre-lox system and viral vectors to express channelrhodopsin-2 in nucleus basalis cholinergic neurons.
- Optogenetically targeted cholinergic axons projecting to the neocortex.
- Stimulated expressing neurons with blue light and recorded local field potentials in anesthetized mice.
Main Results:
- Selective expression of channelrhodopsin-2 in cholinergic neurons and their axons was confirmed.
- Illumination of the neocortex with blue light induced neuronal depolarization and desynchronization of local field potentials.
- Observed effects indicate light-evoked, selective release of acetylcholine (ACh).
Conclusions:
- A novel optogenetic technique allows for the selective stimulation of cholinergic neurotransmission in the neocortex.
- This method overcomes previous limitations of non-specific neurotransmitter release.
- The technique provides a powerful new tool for studying the physiological roles of ACh in the neocortex.
