A NEW TWIST IN AN OLD STORY - THE ROLE FOR CROSSTALK OF NEURONAL AND TROPHIC ACTIVITY

A number of recent findings suggest a reciprocal interaction between n eurotransmitters and neurotrophins functioning at the level of the syn apse, which may be relevant not only for plasticity changes in the mat ure nervous system, but also for the development of synaptic connectiv ity and for survival or maturation of neurons prior to target contact. Thus, neurotrophin-induced attenuation of frequency-dependent depleti on of releasable synaptic vesicle pools of neurotransmitter at synapse s may participate in Hebbian and non-Hebbian forms of LTP, as a charac teristic of mature synaptic contacts. Subsequent to nerve/ target cont act, neurotrophins also appear to mediate contact-induced enhancement of neurotransmitter release; this may participate in a developmental i mprovement of synapse efficacy, stabilization of synaptic contacts, an d maturation of ''conductive'' functional synapses. Coincident with a transmitter-induced elevation of cytosolic Ca2+ levels within growth c ones, a local neurotrophin-mediated increase in released neurotransmit ter occurring subsequent to stabilization of a distinct synaptic conta ct may then participate in the refinement of synapses with retention o f those neurites affected by neurotrophins and withdrawal of those neu rites not affected by neurotrophins. Finally, prior to nerve/target co ntact, Ca2+ channel-generated spontaneous neuronal activity as well as co-expression of neurotrophins and their receptors may play a role in maturational changes. (C) 1997 Elsevier Science Ltd.