Sex steroids and acetylcholine release in the hippocampus

The hippocampus is processing contextual and spatial information in behaving animals. Various environmental stimuli, such as exploration, stress, or learning, increase acetylcholine (ACh) release to activate hippocampal functions. In this chapter, we review the in vivo ACh release property and the physiological function in the hippocampus. By monitoring 24-h ACh release profile in the hippocampus, we found a sex-specific and time-dependent ACh release property, providing a neural basis of sex-specific and time-dependent hippocampal function. In both sexes of rats, gonadectomy, known to impair the hippocampal function, dissociated the appropriate timing of the ACh release and attenuated the release amount. However, testosterone in gonadectomized males or estradiol in gonadectomized females restored the timing and maintained the amount of ACh release. Although the contributing sex hormone was sex-specific, neonatal 17beta-estradiol treatment in female pups successfully masculinized the contributing hormone. Moreover, some rearing conditions affected the sex-specific ACh release, since the influence was sex-specific. These results suggest that (1) estrogen receptor mediates neonatal sexual differentiation of septohippocampal cholinergic system and (2) time of day, circulating sex hormone, and rearing conditions affect the sex-specific ACh release in the hippocampus.