We have evidence that neuronal activity, including that driven by afferent input, regulates acquisition and loss of the DA Ganetespib phenotype by substantia nigra pars compacta (SNc) neurons in adult mice. Hypotheses The aims of the present study were to determine whether the environment or behavior regulates the number of SNc DA neurons in adult mice, and whether this is mediated by
afferent input. Methods Adult mice were subject to two different environments/behaviors: “mating” for 1 week or “environment enrichment” (EE) for 2 weeks; then the Inhibitors,research,lifescience,medical numbers of tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) immunopositive (TH+) and immunonegative (TH−) SNc neurons were counted. Results More TH+ neurons were present in mated males whereas less TH+ neurons were present in mated females. Also, more TH+ neurons were Inhibitors,research,lifescience,medical present in EE males, and this increase was completely abolished by concurrent local infusion of GABAA receptor antagonists. Conclusions The number of DA neurons in the adult SNc is not fixed, but readily increases and decreases in response to environmental stimuli and/or behaviors. These changes are mediated Inhibitors,research,lifescience,medical by afferent
input relaying information about the environment or behavior to SNc neurons. Keywords: Dopamine, midbrain, plasticity Introduction Behavioral adaptation to our environment is mediated by changes in our nervous system. In adults these changes include altered connectivity between neurons (synaptic plasticity) and limited generation of new neurons (neurogenesis). There is, however, evidence of another form of “plasticity,”
Inhibitors,research,lifescience,medical which involves neurons changing the levels of expression of, or identity of their neurotransmitter (Zigmond et al. 1980; Baker et al. 1983; Black et al. 1985, 1987; Richard et al. 1988; Biguet et al. 1989; Schalling et al. 1989; Liaw et al. 1992; Aumann et al. 2011; Dulcis et al. 2013). For example, acquisition or loss of the capacity of hypothalamic Inhibitors,research,lifescience,medical neurons to synthesize and more release dopamine (DA) in response to environmental stimuli has functional and behavioral consequences for adult rats (Dulcis et al. 2013). We too have reported evidence for acquisition and loss of the DA phenotype by adult substantia nigra pars compacta (SNc) neurons in response to altered neuronal activity (Aumann et al. 2008, 2011) or following 6-hydroxy-dopamine Brefeldin_A (6-OHDA) lesions (Stanic et al. 2003). Our data further suggest that afferent input to SNc regulates this “DA phenotype switching” (Aumann et al. 2011). This implicates behavior and/or the environment in regulating the number of DA neurons in the adult SNc, via afferent input. The aims of the present study were to determine: (1) whether the number of SNc DA neurons changes in mice undergoing natural behaviors; (2) which kinds of behavior best induce these changes; and (3) whether afferent input is involved.