Environmental and behavioral modulation of the number of substantia nigra dopamine neurons in adult mice

Abstract

BackgroundRecent evidence indicates that hypothalamic neurons acquire or lose the capacity to synthesize and release dopamine (DA) in response to environmental stimuli, and this has functional and behavioral consequences for adult rats. We have evidence that neuronal activity, including that driven by afferent input, regulates acquisition and loss of the DA 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.MethodsAdult mice were subject to two different environments/behaviors: “mating” for 1 week or “environment enrichment” (EE) for 2 weeks; then the numbers of tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) immunopositive (TH+) and immunonegative (TH−) SNc neurons were counted.ResultsMore TH+ neurons were present in mated males whereas less TH+ neurons were present in mated females. Also, more TH+ neurons were present in EE males, and this increase was completely abolished by concurrent local infusion of GABAA receptor antagonists.ConclusionsThe 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 by afferent input relaying information about the environment or behavior to SNc neurons.

Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice

“…However, EE with GABA A receptor antagonist infusion (either 10 µM picrotoxin or 5 µM bicuculline) completely abolished this increase (right two columns in Figure 2). Note, these data are from the SNc contralateral to the infusion cannula, and are almost identical to the effects observed in the ipsilateral SNc which were reported in 6 . Figure 1: Effects of gender pairing on the number of SNc TH+ neurons.…”

“…These data were previously published in 6 . The present data were compiled in replicate experiments performed as part of that previous study, but have not been published elsewhere.…”

“…changes in density of oxytocin, vasopressin and corticotrophin-releasing hormone cells in hypothalamus 9 ). Indeed, after 7 days of continuous pairing with the opposite gender, we show here and elsewhere 6 (1) DA neurogenesis in the adult mouse midbrain occurs either not at all [10][11][12][13][14] , or at rates much lower than can account for the addition of approximately 500 new SNc DA neurons in a week 15,16 . (2) Studies quantifying changes in number of SNc neurons following 2 week infusions of various drugs targeting the electrical activity of midbrain neurons have consistently revealed equal (again approximately 10%) but opposite changes TH+ and TH-cells, resulting in no net change in the total cell number 4,5 .…”

“…Our hypothesis was they are also associated with longer-lasting changes in midbrain DA signaling brought about by changes in the number of midbrain DA neurons. Here and elsewhere 6 , evidence is presented that this is indeed the case.…”

“…Possibilities include sex steroids, which may underlie both the baseline differences in number of TH+ midbrain neurons in males and females, as well gender-specific changes (increases in males and decreases in females) following pairing reported here and previously 6 . Another possibility is activity-dependent regulation of TH expression.…”