Experience-dependent increase in cAMP-responsive element binding protein in synaptic and nonsynaptic mitochondria of the rat hippocampus.

Cyclic AMP-responsive element binding protein (CREB) plays a pivotal role in the formation of long-term memory in Drosophila, Aplysia, mice and rats. Recently, we were able to demonstrate that CREB and its serine 133 phosphorylated form p-CREB are localized in synaptic and nonsynaptic mitochondria of the rat brain. Here we report on the effect of a one-trial inhibitory avoidance training procedure on mitochondrial CREB from the rat hippocampus. This aversively motivated training task is associated with a time-dependent increase (34-35%) in both p-CREB and CREB immunoreactivities detected in synaptic mitochondria of the hippocampus. In nonsynaptic mitochondria, p-CREB levels increased in both trained and shocked animals. In addition to CREB, two CRE-element binding repressors, CREB-2 and CREM-1, were also detected in purified brain mitochondria. No changes were observed in CREB-2 and CREM-1 immunoreactivities in hippocampal synaptic mitochondria after an inhibitory avoidance training. Taken together the present findings represent the first evidence showing that brain mitochondrial CREB may participate in plasticity-dependent changes associated with a behavioural training procedure.