ABSTRACT
The neurotrophin family of signaling proteins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT)-3, and NT-4/5 have long been recognized as playing a critical role in the survival, differentiation, and outgrowth of select peripheral and central neuron populations during development (Davies, 1994; Levi Montalcini, 1987; Lindsay, 1996; Lewin and Barde, 1996). Neurotrophins continue to be expressed widely in the adult brain, yet the functions of neurotrophins in the adult brain have been hard to define. Recent breakthroughs suggest a broad role for neurotrophins in regulating the structure and function of both developing and adult neural networks (Thoenen, 1995; Prakash et al., 1996; Lewin and Barde, 1996). A core hypothesis is that neurotrophins regulate activity-dependent synaptic plasticity (Thoenen, 1995). Empirical support has come in a spate of studies on two widely studied forms of activity-dependent synaptic plasticity: long-term potentiation (LTP) of synaptic transmission in the hippocampus and synaptic stabilization in the developing visual cortex (Akaneya et al., 1997; Cabelli et al., 1997; Cabelli et al., 1995; Bonhoeffer, 1996). Focusing on the hippocampus, this chapter will highlight recent advances pointing to a causal role for neurotrophins in longterm potentiation of excitatory synaptic transmission. Finally, some implications of these findings for neurotrophin-based management of Alzheimer’s disease will be considered.
