Hormonal Effects on Hippocampal Synaptic Structure and Function

Research in my lab is directed toward understanding the interaction(s) between endocrine rhythms and the limbic system of the mammalian brain. Specifically, we study how fluctuating levels of the ovarian steroid hormones, estradiol and progesterone, regulate structure and function of hippocampal circuitry. The hippocampus is a brain region that normally plays an important role in cognitive and sensory information processing and, under pathological conditions, is a circuit that can generate and propagate seizure activity. Our research uses a multi-disciplinary approach that combines light and electron microscopy, electrophysiological recording from hippocampal slices and behavioral testing to understand the "hows" and "whys" of steroid hormone regulation of synaptic connectivity within the hippocampus.

We have found that concerted action of estradiol and progesterone regulates excitatory input to a major group of hippocampal output cells, the CA1 pyramidal cells. Hormone-induced changes in the density and number excitatory synaptic contacts on CA1 pyramidal cells are associated with increased sensitivity to excitatory synaptic input, enhanced synaptic plasticity, and greater susceptibility to seizure activity.

Thus, by regulating the physical substrates of information flow in the brain: dendrites, axons and the synapses that connect them, steroid hormones such as estradiol and progesterone may predispose neural circuitry to function differently in different hormonal states. Our aim is to understand how hormone-induced structural and functional plasticity regulates both normal an pathological brain function.

Hart, S.A., Snyder, M.A., Smejkalova, T. and C.S. Woolley (2007) Estrogen mobilizes a subset of estrogen receptor- a -immunoreactive vesicles in inhibitory presynaptic boutons in hippocampal CA1. J. Neurosci., 27(8): 2102-2111.

Woolley, C.S. (2007) Acute Effects of Estrogen on Neuronal Physiology.  Annual Reviews of Pharmacology and Toxicology 47: 657-680.

Cooke, B.M., and C.S. Woolley (2005) Gonadal hormone dependent structural plasticity of dendrites in the mammalian CNS. J. Neurobiol 64: 34-46. (cover illustration)

Ledoux, V.L. and C.S. Woolley (2005) Evidence that disinhibition is associated with a decrease in number of vesicles available for release at inhibitory synapses. J. Neurosci. 25(4): 971-976.

Cooke, B.M. and C.S. Woolley (2005) Sexually Dimorphic Synaptic Organization of the Medial Amygdala. J. Neurosci. 25(46): 10759-10767.

Rudick, C.N., R.B. Gibbs and C.S. Woolley, "A role for the basal forebrain cholinergic system in estrogen-induced disinhibition of hippocampal pyramidal cells," J. Neurosci. 23(11): 4479-4490, (2003).

Rudick, C.N. and C.S. Woolley, "Selective estrogen receptor modulators regulate phasic activation of hippocampal CA1 pyramidal cells by estrogen," Endocrinology 144(1): 179-187, (2003)

Yankova, M., S.A. Hart and C.S. Woolley, " Estrogen increases synaptic connectivity between single presynaptic inputs and multiple postsynaptic CA1 pyramidal cells: a serial electron microscopic study," Proceedings of the National Academy of Science, USA 98(6): 3525-3530, (2001) (cover illustration)

Rudick, C.N. and C.S. Woolley, "Estrogen regulates functional inhibition of hippocampal CA1 pyramidal cells in the adult female rat," J. Neurosci., 21(17): 6532-6543, (2001)

Hart, S.A., J.D. Patton and C.S. Woolley, "Quantitative analysis of ERa and GAD co-localization in the hippocampus of the adult female rat," J. Comp. Neurol. 440(2), pp. 144-155, (2001).

Woolley, C.S., "Effects of estrogen in the CNS," Cur. Opin. Neurobiol. 9(3): 349-354, (1999).

View all publications by publications by Catherine S. Woolley listed in the National Library of Medicine (PubMed).