Estrogen-induced remodeling of hypothalamic neural circuitry

For decades, sexual behavior has been a valuable model system for behaviora l neuroscientists studying the neural basis of motivated behaviors. One str iking example of a change in motivation is the binary switch in sexual rece ptivity that occurs during the estrous cycle in female rats. Investigations of the neural basis of this change in behavior have fundamentally advanced our understanding of both behaviorally relevant neural pathways and basic mechanisms of steroid action in the brain. These advances have made this be havioral model system a staple of neuroendocrinology. A challenge that rema ins before us, given our current understanding of the circuitry and chemist ry, is to develop a coherent model of how neural plasticity in the hypothal amus contributes to the dependence of this behavior on motivational state. This review will focus on the ventromedial nucleus of the hypothalamus, esp ecially its ventrolateral subdivision. First, the anatomical, neurochemical , and functional aspects of the macro- and microcircuitry of this brain reg ion will be discussed, followed by a discussion of the likely mechanisms of estrogen action within the ventrolateral VMH. Then, the evidence for estro gen-induced neural plasticity will be considered, including a comparison wi th the effects of estrogen on synaptic organization in other brain regions. Finally, a working model of neural plasticity within the ventrolateral VMH microcircuitry will be presented as a starting point for future experiment s to verify or, more likely, revise and expand.