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

Abstract

Background: Recent 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.

Methods: ADULT 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.

Results: More 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.

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 by afferent input relaying information about the environment or behavior to SNc neurons.

Keywords: Dopamine; midbrain; plasticity.

Figure 1

Changes in the number of tyrosine hydroxylase immunopositive (TH+) neurons in the adult mouse midbrain with mating behavior. Mean ± SE number of TH+ neurons in the substantia nigra pars compacta (SNc;A), ventral tegmental area (VTA;B), and locus ceruleus (LC;C). Differences between control and mated mice within each gender were observed only in the midbrain (SNc and VTA), not in the noradrenergic LC. Mated males had more midbrain TH+ neurons whereas mated females had less midbrain TH+ neurons. Also, control females had more midbrain TH+ neurons than control males. *, significant difference, ns, no significant difference (two-way ANOVA with Tukey multiple comparisons, see Table 1). SE, standard error; ANOVA, analysis of variance.

Figure 2

Changes in the number of tyrosine hydroxylase immunopositive (TH+) neurons in the adult mouse midbrain with environment enrichment. Mean ± SE number of TH+ neurons in the substantia nigra pars compacta (SNc;A), ventral tegmental area (VTA; B), and locus ceruleus (LC;C). Data are from adult male mice only. Differences between standard housed (SH), running wheel only (RW), and environment-enriched (EE) mice were observed only in the midbrain (SNc and VTA), not in the noradrenergic LC. More TH+ neurons were observed in RW mice compared with SH mice in VTA, and EE resulted in further increases in TH+ neurons in both SNc and VTA. *Significant difference (one-way ANOVA with Tukey multiple comparisons, see Table 2). SE, standard error; ANOVA, analysis of variance.

Figure 3

GABA_A receptor blockade completely abolishes the environment enrichment-induced increase in number of tyrosine hydroxylase immunoreactive (TH+) neurons in the substantia nigra pars compacta (SNc). (A) Photomicrographs through SNc showing TH immunoreactive neurons (black reaction product) in SH and EE mice receiving local infusion into SNc of vehicle or the GABA_A receptor antagonist 5 μmol/L bicuculline. SNr, substantia nigra pars reticulata; VTA, ventral tegmental area; *damage caused by the infusion cannula (the infusion cannula was located at a different rostrocaudal level of SNc in the other sections). (B) Mean ± SE number of TH+ SNc neurons in mice subjected to different environments (SH or EE) and different drug infusions (vehicle, 10 μmol/L picrotoxin, or 5 μmol/L bicuculline). *Significant difference (two-way ANOVA with Tukey multiple comparisons, see Table 3) between vehicle- and picrotoxin-infused mice (the same differences exist between vehicle- and bicuculline-infused mice also, but are not shown). SE, standard error; ANOVA, analysis of variance; SH, standard housed; EE, environment-enriched.