Margaret M. McCarthy, Ph.D.
Laboratory of Behavioral Neuroendocrinology
See also Program in Neuroscience
Steroid hormones produced by the gonads and adrenals exert profound influences on the brain both during development and in adulthood. In the rodent there is a neonatal "sensitive" period during which steroids can permanently alter brain morphology and neurochemistry and this in turn regulates a myriad of sex differences in the adult. The cellular and molecular mechanisms that induce these changes are virtually unknown and it is the goal of this laboratory to elucidate those factors that regulate brain differentiation. Using laboratory rodents as an animal model allows for investigation into the control of sexually dimorphic patterns of aggression, anxiety, sexual receptivity and parenting, and thus further our understanding of steroid hormone action in the human brain and its impact on neurological processes. We are currently testing the hypothesis that steroid regulation of the amino acid transmitters, GABA and glutamate, is a fundamental regulatory component of the differentiation process. Steroids can increase or decrease excitatory tone in the brain by altering the ratio of inhibitory to excitatory neurotransmission. This hypothesis is based on previous observations made by us and others that both GABA and glutamate are critically involved in the regulation of two sexually differentiated parameters, the control of the LH-surge at proestrus in the female and sex-specific reproductive behaviors. The use of in situ hybridization histochemistry and the RNase protection assay, which allow for cellular localization and quantification of mRNA, is being used to quantify the synthetic enzymes for GABA and the subunit components of the GABA and glutamate receptors in specific regions of the neonatal brain. Observed changes in gene expression are then tested for causality by administration directly into the neonatal brain of synthetic antisense oligodeoxynucleotides to specific mRNAs.
An additional focus of this laboratory is the potential role played by glial cells in the sexual differentiation of the brain. Sexually dimorphic brain areas have been shown to possess specialized glial cells that exhibit a property defined as phasic synaptic remodeling, which allows for short-term changes in neuronal activity. We are investigating the steroid sensitivity of these cells during development and attempting to determine the mechanism(s) by which early events influence steroid action in the adult brain.
Recent Publications
McCarthy MM, Masters DB, Rimvall K, Schwartz-Giblin S, Pfaff DW 1994 Modulation of female reproductive behavior by infusion of antisense oligodeoxynucleotides for two different genes for GAD. Brain Research 636:209-220.
McCarthy MM 1995 Functional significance of steroid modulation of GABAergic neurotransmission: Analysis at the behavioral, cellular and molecular level. Hormones and Behavior 29:131-140.
Mong JA, Kurzweil RL, Davis AM, Rocca MS, McCarthy MM 1996 Evidence for sexual differentiation of glia in rat brain. Hormones and Behavior 30:553-562.
McCarthy MM, Davis AM, Mong JA 1997 Excitatory neurotransmission and sexual differentiation of the brain. Brain Research Bulletin 44: 487-496.
