Viktor Hamburger Award review. Environmental regulation of brain trophic interactions

Emerging evidence indicates that trophic interactions that influence brain development are critical throughout life, mediating processes as diverse as learning, memory and regrowth after injury. This review summarizes recent work suggesting that impulse activity regulates trophic interactions in the brain, allowing the conversion of millisecond-to-millisecond signalling into long-term changes in neural circuit function. For example, depolarizing stimuli regulate trophic factor gene expression, an effect mediated by excitatory transmitters. Responsiveness to trophic factors is also regulated by activity, since depolarization increases the expression of trophic receptor genes. Moreover, different excitatory transmitter receptor subtypes mediate trophic or regressive effects, allowing a neural system to precisely memorialize excitatory or inhibitory experiences. A number of open questions are articulated to define potential future directions.