Ketamine produces rapid antidepressant action in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here Fuchikami and colleagues studied if modulation of neuronal activity in the infralimbic prefrontal cortex underlies the antidepressant and anxiolytic actions of ketamine. Neuronal inactivation of the infralimbic prefrontal cortex completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models; ketamine microinfusion into infralimbic prefrontal cortex reproduced behavioral actions of systemic ketamine. Optogenetic stimulation of the infralimbic prefrontal cortex produced rapid and long-lasting antidepressant and anxiolytic effects. These effects were associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of infralimbic prefrontal cortex are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.
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Fuchikami M, Thomas A, Liu R, Wohleb ES, Land BB, DiLeone RJ, Aghajanian GK and Duman RS: Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. PNAS 112(26): 8106-8111 (2015).
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http://www.ncbi.nlm.nih.gov/pubmed/26056286