Estrogen acts on maternal circuitry to establish maternal behaviour in otherwise non-maternal rats. The precise mechanisms by which estrogen primes maternal circuitry are unknown; however, the medial preoptic area (MPOA) stimulates maternal behaviour whilst the medial amygdala (MeA) inhibits it. This thesis aimed to address the link between estrogen sensitivity, astroglia and maternal behaviour. Maternal care influences maternal behaviour of female offspring. One mechanism underlying this influence is differential estrogen sensitivity within the MPOA. Estrogen receptor alpha (ERalpha) expression was examined in offspring of High and Low licking/grooming (LG) dams within the MPOA. Enhanced expression ERalpha was limited to the medial preoptic nucleus in offspring of High LG dams and the anteroventral periventricular nucleus in Low LG dams. Adult nulliparous offspring of High and Low LG dams were assessed for maternal responsiveness using the pup sensitization paradigm. Offspring of Highs showed maternal behaviour significantly earlier than offspring of Lows. Brains of pup-exposed and pup-naive High and Low offspring were analyzed for astroglial markers glial fibrillary acidic protein (GFAP) and glutamine synthetase. Pup-naive animals showed more GFAP positive cells within the posteroventral MeA, with no differences within the MPOA and no effect of maternal care. Glutamine synthetase, a glial-derived enzyme necessary for glutamate production, showed greater expression within the MeA of High LG pup-naive animals; with no maternal care differences observed in pup-experienced animals. Thus, long-lasting changes within maternal circuitry established in early life are reflected in regionally specific enhanced estrogen sensitivity and latency to display maternal behaviour, but the effects are less clear with respect to astroglia.

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We are interested in understanding the molecular mechanisms that govern synaptic growth and plasticity. Recent evidence from several laboratories suggests that small GTPases play an important role in the promotion of neurite outgrowth; however, their role in the control of synaptic growth and functional plasticity is not well understood. The goal of this thesis is to investigate the role of small GTPases (including Rac, Rho and Cdc42) in the regulation of synaptic growth in vivo, using the Drosophila larval neuromuscular junction (NMJ) synapses as a model system. Our results show that presynaptic overexpression of Rac, but not of Rho or Cdc42, positively regulates both synaptic structure and function. Genetic loss of Rac leads to embryonic lethality, making it impossible to assess the full loss-of-function phenotype using conventional mutants. To circumvent this, we use the MARCM (Mosaic Analysis with a Repressible Cell Marker) technique to generate single motor neuron clones devoid of all genetic copies of Rac. Our data suggest that Rac activity is crucial for normal synaptic development. In support of this conclusion, we demonstrate that genetic removal of trio, a guanine nucleotide exchange factor (GEF) that is known to activate Rac, leads to a drastic reduction in the number of synaptic boutons. In addition, genetic removal of one copy of trio is sufficient to suppress the gain-of-function phenotype of Rac. Moreover, we demonstrate that partial removal of the fragile X mental retardation gene (dfmr1), a known suppressor of Rac, enhances the gain-of-function phenotype of Rac. Taken together, our findings support a model in which Rac signaling positively regulates synaptic growth and function at the Drosophila larval NMJ.

No description available.