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

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Abstract
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.