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J Neurosci DOI:10.1523/JNEUROSCI.0092-12.2013

Cortical control of affective networks.

Publication TypeJournal Article
Year of Publication2013
AuthorsKumar, S, Black, SJ, Hultman, R, Szabo, ST, DeMaio, KD, Du, J, Katz, BM, Feng, G, Covington, HE, Dzirasa, K
JournalJ Neurosci
Date Published2013 Jan 16
KeywordsAffect, Animals, Anxiety, Behavior, Animal, Cerebral Cortex, Male, Mice, Nerve Net, Neurons

Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thy1-Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thy1-Chr2 mice: an effect that is observed >10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy1-Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders.


Alternate JournalJ. Neurosci.
PubMed ID23325249
PubMed Central IDPMC3711588
Grant ListP50 MH060451 / MH / NIMH NIH HHS / United States
R37MH073853 / MH / NIMH NIH HHS / United States
RC1 MH088434 / MH / NIMH NIH HHS / United States
RC1-MH088434 / MH / NIMH NIH HHS / United States
R37 MH073853 / MH / NIMH NIH HHS / United States
P50MH060451-09S1 / MH / NIMH NIH HHS / United States