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 neurotransmitters and neurotrophins functioning at the level of the synapse, which may be relevant not only for plasticity changes in the mature nervous system, but also for the development of synaptic connectivity and for survival or maturation of neurons prior to target contact. Thus, neurotrophin-induced attenuation of frequency-dependent depletion of releasable synaptic vesicle pools of neurotransmitter at synapses may participate in Hebbian and non-Hebbian forms of LTP, as a characteristic of mature synaptic contacts. Subsequent to nerve/target contact, neurotrophins also appear to mediate contact-induced enhancement of neurotransmitter release; this may participate in a developmental improvement of synapse efficacy, stabilization of synaptic contacts, and maturation of "conductive" functional synapses. Coincident with a transmitter-induced elevation of cytosolic Ca2+ levels within growth cones, a local neurotrophin-mediated increase in released neurotransmitter occurring subsequent to stabilization of a distinct synaptic contact may then participate in the refinement of synapses with retention of those neurites affected by neurotrophins and withdrawal of those neurites not affected by neurotrophins. Finally, prior to nerve/target contact, Ca2+ channel-generated spontaneous neuronal activity as well as co-expression of neurotrophins and their receptors may play a role in maturational changes.