A new mechanism of synapse-specific neuronal plasticity.

According to current concepts, long-term memory is based on structural-functional changes in particular synaptic connections between neurons in the brain (synapse-specific plasticity), which depend on the processes of translation and transcription. Studies on neurons in the mollusk Aplysia and the mammalian hippocampus have addressed a mechanism of synapse-specific plasticity which does not require synapse-specific molecular genetic processes. Stimulation of a synapse has been shown to lead to activation of intracellular second messengers in the synapse as well as "synaptic tagging"--the formation of mechanisms "recognizing" transcription products. In the neuron body, second messengers induce the synthesis of RNA and protein molecules which are widely distributed in neuron processes and which are inserted selectively only into stimulation-tagged synapses, evoking long-term changes in their functional and morphological characteristics. The results of our studies on common snail defensive behavior command neurons LPl1 and RPl1 suggest the existence of another mechanism controlling synapse-specific plasticity. On acquisition of sensitization, a number of second messengers and the genes controlled by them are involved in supporting the plasticity of defined synaptic inputs of these neurons in snails. The processes of induction of long-term facilitation in the sensory inputs of neurons from chemoreceptors on the head have been shown to involve cAMP and cAMP-dependent transcription factors of the immediate early gene C/EBP (CAAT/enhancer binding protein), while the mechanisms controlling the other sensory input of neurons LPl1 and RPl1--from mechanoreceptors on the head--involve protein kinase C and protein kinase C-dependent transcription factor SRF (serum response factor). The immediate early gene zif268 is involved in controlling the inputs from both chemo-and mechanoreceptors on the head. These results are regarded as experimental support for the hypothesis that the molecular mechanisms of synapse-specific plasticity during learning may form on the basis of a selective neurochemical "projection" of the synaptic connections onto defined genes in the neuron.