The main objective of the research conducted in my laboratory is to identify cell biological correlates of behavior. Specifically, we are investigating the effects of the hormone estrogen on areas of the brain controlling rat female reproductive behavior, i.e., lordosis.
Lordosis is a steroid-dependent mating behavior that requires estrogen action in a specific group of cells within the ventromedial nucleus (VMN) of the rat hypothalamus. Estrogen sets in motion a cascade of events that, together with the appropriate sensory input, results in the dorsiflexion of the vertebral column and rump elevation required for intromission by the male. Because of its dependence on estrogen action in the CNS, lordosis is not a simple reflex. In fact, the sophistication of the system, in terms of the integration of sensory and hormonal events necessary for execution of the behavior and its implication in human behaviors such as mood changes, makes it an intriguing model for the elucidation of other complex human behaviors.
In the hypothalamus, hormonal influences by estrogen and progesterone mobilize the biosynthetic apparatus of VMN neurons in such a way that the manner in which these neurons transmit information (e.g., via neuropeptide and/or neurotransmitter biosynthesis, transsynaptic influences) or receive signals (e.g. alterations at the receptor level, conformational changes in phosphoproteins, morphological changes in synapses) is significantly altered. Our research focuses on the detection of synthetic mechanisms in the VMN, their possible modes of regulation and the identity of specific estrogen-induced proteins. Recently, we have shown that the VMN has the capability for producing nitric oxide (NO), an important molecule in central nervous system function. This gas neuromessenger is synthesized from the amino acid L-arginine by the constitutive enzyme nitric oxide synthase (NOS). Lately, attention has been focused on the involvement of NO in retrograde signalling, the enhancement of synaptic transmission at neighboring synapses and cytotoxicity. Our findings indicate that NOS is localized to neurons containing the estrogen receptor in the VMN. We are presently examining the regulation by estrogen of this enzyme and the role of NO in female reproductive behavior. We propose that the synthesis and/or activation of NO by estrogen provides a link between neuroendocrine and neuronal mechanisms involved in lordosis behavior.
Publications:
1.Rogalski-Wilk, A.A. and Cohen, R.S. 1997. Glyceraldehyde-3-phosphate dehydrogenase activity and F-actin associations in synaptosomes and postsynaptic densities of porcine cerebral cortex. Cellul. Molecul. Neurobiol. 17:51-70.
2.Rachman, I.M., Pfaff, D.W. and Cohen, R.S. 1996. NADPH diaphorase and nitric oxide synthase immunoreactivity in lordosis-relevant neurons of the ventromedial hypothalamus. Brain Res. 689:291-306.
3. Cohen, R.S. and Pfaff, D.W. 1992. Ventromedial hypothalamic neurons in the mediation of long-lasting effects of estrogen on lordosis behavior. Prog. Neurobiol. 38:423-453.
4. Benevento, L.A., Bakkum, B.W., Port, J.D. and Cohen, R.S. 1992. The effects of dark-rearing on the electrophysiology of the rat visual cortex. Brain Res. 572:198-207.
5. Bakkum, B.W., Benevento, L.A. and Cohen, R.S. 1991. Effects of light dark- and dark-rearing on synaptic morphology in the superior colliculus and visual cortex of postnatal and adult rat. J. Neurosci. Res. 28:65-80.