Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions

Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-06, Vol.112 (26), p.8106-8111
Main Authors: Fuchikami, Manabu, Thomas, Alexandra, Liu, Rongjian, Wohleb, Eric S., Land, Benjamin B., DiLeone, Ralph J., Aghajanian, George K., Duman, Ronald S.
Format: Article
Language:English
Subjects:
Animal behavior
Animals
Antidepressants
Antidepressive Agents - pharmacology
Behavior, Animal - drug effects
Biological Sciences
Brain
Ketamine - pharmacology
Limbic System - drug effects
Limbic System - physiopathology
Male
Neurons
Optogenetics
Prefrontal Cortex - drug effects
Prefrontal Cortex - physiopathology
Rats
Rats, Sprague-Dawley
Rodents
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Summary:Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1414728112