Neurotrophin Modulation of Hippocampal Synaptic Transmission

Abstract

Publisher Summary Nerve growth factor (NGF) and related members of the neurotrophin gene family are essential for the selective survival and differentiation of specific neurons within the peripheral and central nervous systems. This chapter summarizes several recent studies that suggest a novel role for these trophic factors in the dynamic modulation of synaptic efficacy, both during development and in maturity. The neurotrophin gene family includes NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). Three trk family members, trkA , trkB , and trkC , encode essential components of receptors for these neurotrophins. Neurotrophin receptors exist in several isoforms. The full-length, active forms of the trk family are necessary for the normal development and maintenance of specific neuronal populations. To investigate underlying synaptic mechanisms, the BDNF effect has been characterized in whole-cell voltage-clamp experiments. Recordings of excitatory postsynaptic currents (EPSCs) revealed a marked enhancement within 2-3 min of BDNF exposure. BDNF application has elicited a twofold increase in synaptic charge with a time course similar to the increase in action potential activity. Anoother neurotrophin NT-4, ligands at the trkB receptor, has also rapidly increased both the frequency and amplitude of excitatory synaptic currents in hippocampal neurons. The potentiation of synaptic current amplitude, in particular, results from a phosphorylation-dependent change in postsynaptic responsiveness. Neurotrophins have also been shown to enhance synaptic transmission by increasing presynaptic transmitter release. These results suggest that trophic factors may play a central role in the dynamic modulation of synaptic efficacy. Acute modulation by neurotrophins may constitute an intermediary stage, preceding more stable changes that depend on alterations in gene expression and/or protein synthesis.