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Updated: Jun 13, 2026

Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice
Published on: October 27, 2020
A neurochemical yin and yang: does serotonin activate and norepinephrine deactivate the prefrontal cortex?
1The Zanvyl Krieger Mind/Brain Institute, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218, USA. pfitz@mbi.mb.jhu.edu
Introduction:
The prefrontal cortex (PFC) receives serotonergic input from the dorsal raphe nucleus of the brainstem, as well as noradrenergic input from another brainstem nucleus, the locus coeruleus. A large number of studies have shown that these two neurotransmitter systems, and drugs that affect them, modulate the functional properties of the PFC in both humans and animal models.
Results:
Here I examine the hypothesis that serotonin (5-HT) plays a general role in activating the PFC, whereas norepinephrine (NE) plays a general role in deactivating this brain region. In this manner, the two neurotransmitter systems may have opposing effects on PFC-influenced behavior. To assess this hypothesis, three primary lines of evidence are examined comprising the effects of 5-HT and NE on impulsivity, cognitive flexibility, and working memory.
Discussion:
While all of the existing data do not unequivocally support the activation/deactivation hypothesis, there is a large body of support for it.
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