Dysfunctional dopaminergic (DAergic) neurotransmission between the substantia nigra pars compacta (SNc) and the dorsal striatum (the nigrostriatal pathway) causes several prominent movement disorders (e.g. the motor symptoms of Parkinson's disease, dystonias and dyskinesias). Both too much and too little DA signalling can be problematic and nigrostriatal DAergic transmission is maintained at normal levels by several homeostatic mechanisms acting over timescales of milliseconds to weeks: e.g. binding of DA to tyrosine 3-monooxygenase (EC 1.14.16.2) (tyrosine Received November 1, 2010; revised manuscript received December 13, 2010; accepted December 14, 2010. Address correspondence and reprint requests to T. D. Aumann, Florey Neuroscience Institutes, The University of Melbourne, Parkville, Victoria, Australia 3010. E-mail: tim.aumann@florey.edu.auAbbreviations used: D2R, D 2 dopamine receptor; DA, dopamine; EGF, epidermal growth factor; FGF, fibroblast growth factor; GDNF, glial cellderived neurotrophic factor; GFP, green fluorescent protein; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate-buffered saline; RRF, retrorubral field; SDS, sodium dodecyl sulfate; SK, small-conductance, Ca 2+ -activated potassium; SNc, substantia nigra pars compacta; TH, tyrosine hydroxylase; TTX, tetrodotoxin; VTA, ventral tegmental area. AbstractStriatal delivery of dopamine (DA) by midbrain substantia nigra pars compacta (SNc) neurons is vital for motor control and its depletion causes the motor symptoms of Parkinson's disease. While membrane potential changes or neuronal activity regulates tyrosine hydroxylase (TH, the rate limiting enzyme in catecholamine synthesis) expression in other catecholaminergic cells, it is not known whether the same occurs in adult SNc neurons. We administered drugs known to alter neuronal activity to mouse SNc DAergic neurons in various experimental preparations and measured changes in their TH expression. In cultured midbrain neurons, blockade of action potentials with 1 lM tetrodotoxin decreased TH expression beginning around 20 h later (as measured in real time by green fluorescent protein (GFP) expression driven off TH promoter activity). By contrast, partial blockade of small-conductance, Ca 2+ -activated potassium channels with 300 nM apamin increased TH mRNA and protein between 12 and 24 h later in slices of adult midbrain. Twoweek infusions of 300 nM apamin directly to the adult mouse midbrain in vivo also increased TH expression in SNc neurons, measured immunohistochemically. Paradoxically, the number of TH immunoreactive (TH+) SNc neurons decreased in these animals. Similar in vivo infusions of drugs affecting other ion-channels and receptors (L-type voltage-activated Ca 2+ channels, GABA A receptors, high K + , DA receptors) also increased or decreased cellular TH immunoreactivity but decreased or increased, respectively, the number of TH+ cells in SNc. We conclude that in adult SNc neurons: (i) TH expression is activity-dependent and begins to change 20 h following sustained chang...

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Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females.