Behavioral Depression-Related Modifications of the Properties of Glutamatergic Synapses in the Basolateral Amygdalar Nucleus in Rats

Abstract

Behavioral depression evoked by social isolation of experimental rats was accompanied by changes in the properties of glutamatergic synapses in the basolateral amygdalar nucleus, BLAN; the amplitude of field EPSP (fEPSP) decreased, long-term potentiation was intensified, while long-term depression of synaptic transmission was weakened. These modifications could be reproduced in vitro by application of 100 nM deoxycorticosterone or, partially, of 1 μM prednisolone to brain slices of intact rats, but were absent in the case of application of 100 nM dexamethasone. Observed in vivo social isolation-evoked changes in the properties of glutamatergic synapses could be prevented by subcutaneous injections of 2 mg/kg spironolactone (twice a day over 72 h of isolation). In vitro, 2 μM spironolactone eliminated modulating effects of deoxycorticosterone and inverted effects of prednisolone on the plastic properties of glutamatergic synapses. Inhibitors of transcription and ribosomal protein synthesis, doxorubicin (100 μM) and levomycetin (2 mM), respectively, prevented effects of deoxycorticosterone on synaptic transmission. The influence of the latter hormone on synaptic transmission in the BLAN was suppressed by an inhibitor of protein kinase C, polymixin B (50 μM), but significantly increased by an inhibitor of tyrosine phosphatases, sodium orthovanadate (1 mM). Suppression of synaptic transmission, which was evoked by deoxycorticosterone, was not accompanied by changes in the paired-pulse facilitation and amplitude of the NMDA component of fEPSP, while the amplitude of the AMPA component decreased. We suppose that these changes are based on intensification of synthesis of the proteins involved in endocytosis of the AMPA receptors, which results in intensification of endocytosis and a drop in the number of AMPA receptors in the postsynaptic thickenings. These changes of the fundamental properties of synaptic transmission facilitate the development of long-term potentiation of synaptic transmission, but weaken long-term depression of the transmission. The pattern of deoxycorticosterone-induced modifications of the plastic properties of glutamatergic synapses corresponds well to the main statements of the theory of metaplasticity.