Stress and amygdala suppression of metaplasticity in the medial prefrontal cortex.
The term "metaplasticity" refers to the modulation of the ability to induce synaptic plasticity of the form of long-term potentiation (LTP) or long-term depression (LTD) following prior activation of the synapses. While often electrophysiological manipulations are used to demonstrate this phenomenon, prior behavioral manipulations such as exposure to stress were also found to affect the ability to induce LTP and LTD. Interestingly, amygdala stimulation was found to have effects on subsequent LTP induction that resemble those of stress. Here, we report that exposure to stress or basolateral amygdala (BLA) stimulation induces a form of metaplasticity, which prevents the ability of a second episode of stress or BLA activation to suppress LTP in the ventral hippocampus-medial prefrontal cortex (mPFC) pathway. This form of metaplasticity is N-methyl-D-aspartic acid (NMDA)-dependent since the injection of the NMDA partial agonist D-cycloserine prevented the inhibition of LTP induced by prior exposure of stress or BLA activation. Furthermore, blocking NMDA receptors by MK801 before the exposure to stress prevented the ability of the emotional manipulation to inhibit the subsequent modulation of plasticity, resulting in impaired LTP in the mPFC. Taken together, these findings demonstrate a new form of NMDA-dependent emotional metaplasticity in the ventral hippocampus-mPFC pathway.
Richter-Levin
Gal
G
Department of Neurobiology and Ethology, Faculty of Sciences, University of Haifa, Haifa 31905, Israel.
Maroun
Mouna
M
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D003523:Cycloserine / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*
D018683:Excitatory Amino Acid Agents; D016291:Dizocilpine Maleate; D003523:Cycloserine