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The Journal of Neuroscience, May 6, 2009, 29(18):5992-6000; doi:10.1523/JNEUROSCI.0230-09.2009

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Behavioral/Systems/Cognitive
The Basal Forebrain Cholinergic System Is Required Specifically for Behaviorally Mediated Cortical Map Plasticity

Dhakshin Ramanathan,¹ Mark H. Tuszynski,^1,2 and James M. Conner¹

¹Department of Neurosciences, University of California, San Diego, La Jolla, California 92093-0626, and ²Veterans Affairs Medical Center, San Diego, California 92161

Correspondence should be addressed to either Dr. James M. Conner or Dr. Mark H. Tuszynski, Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, Mail Code 0626, La Jolla, CA 92023, Email: jmconner{at}ucsd.edu or Email: mtuszynski{at}ucsd.edu

The basal forebrain cholinergic system has been implicated in the reorganization of adult cortical sensory and motor representations under many, but not all, experimental conditions. It is still not fully understood which types of plasticity require the cholinergic system and which do not. In this study, we examine the hypothesis that the basal forebrain cholinergic system is required for eliciting plasticity associated with complex cognitive processing (e.g., behavioral experiences that drive cortical reorganization) but is not required for plasticity mediated under behaviorally independent conditions. We used established experimental manipulations to elicit two distinct forms of plasticity within the motor cortex: facial nerve transections evoke reorganization of cortical motor representations independent of behavioral experience, and skilled forelimb training induces behaviorally dependent expansion of forelimb motor representations. In animals that underwent skilled forelimb training in conjunction with a facial nerve lesion, cholinergic mechanisms were required for mediating the behaviorally dependent plasticity associated with the skilled motor training but were not necessary for mediating plasticity associated with the facial nerve transection. These results dissociate the contribution of cholinergic mechanisms to distinct forms of cortical plasticity and support the hypothesis that the forebrain cholinergic system is selectively required for modulating complex forms of cortical plasticity driven by behavioral experience.

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Received Jan. 15, 2009; revised Feb. 23, 2009; accepted March 10, 2009.

Correspondence should be addressed to either Dr. James M. Conner or Dr. Mark H. Tuszynski, Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, Mail Code 0626, La Jolla, CA 92023, Email: jmconner{at}ucsd.edu or Email: mtuszynski{at}ucsd.edu

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