Nicholas Brecha, Ph.D.

Detailed Biography
Neurochemical and Anatomical Pathways in the Vertebrate Retina that Mediate Vision Dr. Brecha’s major research interest is concerned with understanding the functional organization of the mammalian retina by elucidating its morphology and neurochemistry. Specific investigations are focused on defining the microcircuitry of the inner retina, evaluating the neurochemical organization and regulation of both its fast (amino acid) and slow (peptide) transmitter systems, and the function of bipolar, amacrine and ganglion cell populations, which are major retinal cell types that play critical roles in the processing of visual information. Recent investigations concerned with peptide-containing cell populations are defining the cellular expression patterns of tachykinin, somatostatin, neuropeptide Y and opiate receptors, and their functional role in modulating bipolar cell responsiveness. Morphological studies have shown that peptide receptor subtypes are selectively expressed by different populations of bipolar, amacrine and ganglion cells. These observations have provided important clues to the organization of the retinal microcircuits mediating different aspects of vision, as well as the sites of action of several previously identified retinal transmitter substances. A new research direction, developed over the past three years has been focused on determining the function of peptides in the retina. The rationale of these studies is to define the cellular actions of peptides found in the retina, which we hypothesize modulate cellular responsiveness, to influence ion channels and other intercellular messenger systems. Initial studies have focused on somatostatin; our findings demonstrate that this peptide inhibits both K+ and Ca2+ ion channels in the axonal terminals of bipolar cells and photoreceptors at low concentrations. Interestingly, these cells prominently express the somatostatin receptor subtype, sst2A suggesting this action is mediated through this receptor. These investigations provide further support for a role of somatostatin in the presynaptic modulation of transmitter release from retinal cells.

Liu Xue, Hirano Arlene A, Sun Xiaoping, Brecha Nicholas C, Barnes Steven Calcium channels in rat horizontal cells regulate feedback inhibition of photoreceptors through an unconventional GABA- and pH-sensitive mechanism The Journal of physiology, 2013; .
Zampighi GA, Schietroma C, Zampighi LM, Woodruff M, Wright EM, Brecha NC Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PLoS One, 2011; 6(3): e16944.
Zampighi Guido A, Schietroma Cataldo, Zampighi Lorenzo M, Woodruff Michael, Wright Ernest M, Brecha Nicholas C Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PloS one, 2011; 6(3): e16944.
Hirano AA, Brandstätter JH, Morgans CW, Brecha NC SNAP25 expression in mammalian retinal horizontal cells J Comp Neurol, 2011; 519(5): 972-88.
Hirano Arlene A, Brandstätter Johann Helmut, Morgans Catherine W, Brecha Nicholas C SNAP25 expression in mammalian retinal horizontal cells The Journal of comparative neurology, 2011; 519(5): 972-88.
Guo C, Hirano AA, Stella SL Jr, Bitzer M, Brecha NC Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter J Comp Neurol, 2010; 518(10): 1674-69.
Guo Chenying, Hirano Arlene A, Stella Salvatore L, Bitzer Michaela, Brecha Nicholas C Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter The Journal of comparative neurology, 2010; 518(10): 1647-69.
Lee H, Brecha NC Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells Eur J Neurosci, 2010; 31(8): 1388-401.
Lee Helen, Brecha Nicholas C Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells The European journal of neuroscience, 2010; 31(8): 1388-401.
Farrell SR, Raymond ID, Foote M, Brecha NC, Barnes S Modulation of voltage-gated ion channels in rat retinal ganglion cells mediated by somatostatin receptor subtype 4 J Neurophysiol, 2010; 104(3): 1347-54.
Raymond ID, Pool AL, Vila A, Brecha NC A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells Vis Neurosci. 2009 Nov;26(5-6):453-65, 2009; 26(5-6): 453-65.
Raymond Iona D, Pool Angela L, Vila Alejandro, Brecha Nicholas C A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells Visual neuroscience, 2009; 26(5-6): 453-65.
Stella SL Jr, Hu WD, Brecha NC Adenosine suppresses exocytosis from cone terminals of the salamander retina Neuroreport, 2009; 20(10): 923-9.
Stella Salvatore L, Hu Wanda D, Brecha Nicholas C Adenosine suppresses exocytosis from cone terminals of the salamander retina Neuroreport, 2009; 20(10): 923-9.
Guo Chenying, Stella Salvatore L, Hirano Arlene A, Brecha Nicholas C Plasmalemmal and vesicular gamma-aminobutyric acid transporter expression in the developing mouse retina The Journal of comparative neurology, 2009; 512(1): 6-26.
Stella Salvatore L, Li Stefanie, Sabatini Andrea, Vila Alejandro, Brecha Nicholas C Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina Brain research, 2008; 1215(1): 20-9.
Raymond Iona D, Vila Alejandro, Huynh Uyen-Chi N, Brecha Nicholas C Cyan fluorescent protein expression in ganglion and amacrine cells in a thy1-CFP transgenic mouse retina Molecular vision, 2008; 14(1): 1559-74.
Anselmi Nicholas C, Stella Nicholas C, Brecha Nicholas C, Sternini Nicholas C Galanin inhibition of voltage-dependent Ca(2+) influx in rat cultured myenteric neurons is mediated by galanin receptor 1 Journal of neuroscience research, 2008; 512(1): 1107-14.
Hirano Arlene A, Brandstätter Johann Helmut, Vila Alejandro, Brecha Nicholas C Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes Visual neuroscience, 2008; 24(4): 489-502.
Stella Salvatore L, Hu Wanda D, Vila Alejandro, Brecha Nicholas C Adenosine inhibits voltage-dependent Ca2+ influx in cone photoreceptor terminals of the tiger salamander retina Journal of neuroscience research, 2007; 85(5): 1126-37.
Wang Yuan, Luksch Harald, Brecha Nicholas C, Karten Harvey J Columnar projections from the cholinergic nucleus isthmi to the optic tectum in chicks (Gallus gallus): a possible substrate for synchronizing tectal channels The Journal of comparative neurology, 2006; 494(1): 7-35.
Casini Giovanni, Rickman Dennis W, Brecha Nicholas C Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in monkey and human retina Investigative ophthalmology & visual science, 2006; 47(4): 1682-90.
Chang Bo, Heckenlively John R, Bayley Philippa R, Brecha Nicholas C, Davisson Muriel T, Hawes Norm L, Hirano Arlene A, Hurd Ronald E, Ikeda Akihiro, Johnson Britt A, McCall Maureen A, Morgans Catherine W, Nusinowitz Steve, Peachey Neal S, Rice Dennis S, Vessey Kirstan A, Gregg Ronald G The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses Visual neuroscience, 2006; 23(1): 11-24.
Hirano Arlene A, Brandstätter Johann H, Brecha Nicholas C Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina The Journal of comparative neurology, 2005; 488(1): 70-81.
D’Angelo I, Brecha NC. Y2 receptor expression and inhibition of voltage-dependent Ca2+ influx into rod bipolar cell terminals, Neuroscience, 2004; 125(4): 1039-49.
Minnis JG, Patierno S, Kohlmeier SE, Brecha NC, Tonini M, Sternini C. Ligand-induced mu opioid receptor and endocytosis and recycling in enteric neurons, Neuroscience, 2003; 119(1): 33-42.
Oh Su-Ja, D’Angelo Iona, Lee Eun-Jin, Chun Myung-Hoon, Brecha Nicholas C Distribution and synaptic connectivity of neuropeptide Y-immunoreactive amacrine cells in the rat retina The Journal of comparative neurology, 2002; 446(3): 219-34.
Casini, G Sabatini, A Catalani, E Willems, D Bosco, L Brecha, NC Expression of the neurokinin 1 receptor in the rabbit retina Neuroscience. , 2002; 115(4): 1309-21.
D’Angelo Iona, Oh Su-Ja, Chun Myung-Hoon, Brecha Nicholas C Localization of neuropeptide Y1 receptor immunoreactivity in the rat retina and the synaptic connectivity of Y1 immunoreactive cells The Journal of comparative neurology, 2002; 454(4): 373-82.
Cueva Juan G, Haverkamp Silke, Reimer Richard J, Edwards Robert, Wässle Heinz, Brecha Nicholas C Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells The Journal of comparative neurology, 2002; 445(3): 227-37.
Kang, WS Lim, MY Lee, EJ Kim, IB Oh, SJ Brecha, NC Park, CB Chun, MH Light- and electron-microscopic analysis of neuropeptide Y-immunoreactive amacrine cells in the guinea pig retina Cell and tissue research. , 2001; 306(3): 363-71.
Casini, G Brecha, NC Bosco, L Rickman, DW Developmental expression of neurokinin-1 and neurokinin-3 receptors in the rat retina The Journal of comparative neurology. , 2000; 421(2): 275-87.
Melone, M Brecha, NC Sternini, C Evans, C Conti, F Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex Neuroscience. , 2000; 100(3): 439-43.
Sternini, C Brecha, NC Minnis, J D’Agostino, G Balestra, B Fiori, E Tonini, M Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors Neuroscience. , 2000; 98(2): 233-41.
Akopian, A., Johnson, J., Gabriel, R., Brecha, N.C. and P. Witkovsky Somatostatin modulates voltage-gated K+ and Ca2+ currents in rod and cone photoreceptors of the salamander retina, Journal of Neuroscience 20:929-936, 2000; 20: 929-936.
Johnson, J Wu, V Wong, H Walsh, JH Brecha, NC Somatostatin receptor subtype 2A expression in the rat retina Neuroscience. , 1999; 94(3): 675-83.
Johnson, J Wong, H Walsh, JH Brecha, NC Expression of the somatostatin subtype 2A receptor in the rabbit retina The Journal of comparative neurology. , 1998; 393(1): 93-101.
Casini, G Rickman, DW Sternini, C Brecha, NC Neurokinin 1 receptor expression in the rat retina The Journal of comparative neurology. , 1997; 389(3): 496-507.
Johnson, J., Chen, T.K., Rickman, D.W., Evans, C., and Brecha, N.C Multiple g-aminobutyric acid plasma membrane transporters (GAT-1, GAT-2 and GAT-3) in the rat retina, Journal of Comparative Neurology, 1996; 375: 212-224.
Rickman, DW Blanks, JC Brecha, NC Somatostatin-immunoreactive neurons in the adult rabbit retina The Journal of comparative neurology. , 1996; 365(3): 491-503.
Brecha, N., Johnson, J., Kui, R., Anton, B., Keith Jr., D., Evans, C., and Sternini, C. Mu opioid receptor immunoreactivity is expressed in the retina and retinal-recipient nuclei, Analgesia, 1995; 1: 331-334.
Corey, JL Davidson, N Lester, HA Brecha, N Quick, MW Protein kinase C modulates the activity of a cloned gamma-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular redistribution of the transporter The Journal of biological chemistry. , 1994; 269(20): 14759-67.

James Bisley, Ph.D.

Dr Bisley received his Ph.D. from the University of Melbourne in Australia where he studied the peripheral somatosensory system. He did his first post-doc at the University of Rochester working with Dr Tatiana Pasternak, where he studied the neural mechanisms underlying memory for motion. In 1999, he went to Washington, DC where he worked with Dr Michael E. Goldberg at Georgetown University and the National Eye Institute, studying the neural mechanisms underlying visuo-spatial attention. Dr Bisley moved to Columbia University with Dr Goldberg in 2002 and joined UCLA in 2006.

Arcizet F., Mirpour K., Foster D.J., Charpentier C.J., Bisley J.W. LIP activity in the inter-stimulus interval of a change detection task biases the behavioral response Journal of Neurophysiology, 2015; jn.00604.2015.
Mirpour K., Bisley J.W. Remapping, Spatial Stability, and Temporal Continuity: From the Pre-Saccadic to Postsaccadic Representation of Visual Space in LIP Cerebral Cortex, 2015; 15(12): .
Zelinsky G.J., Bisley J.W. The what, where, and why of priority maps and their interactions with visual working memory Annals of the New York Academy of Sciences, 2015; 1339(12): 154-64.
Krishna B.S., Ipata A.E., Bisley J.W., Gottlieb J., Goldberg M.E. Extrafoveal preview benefit during free-viewing visual search in the monkey Journal of Vision, 2014; 14(1): .
Mirpour K., Bisley J.W. Evidence for differential top-down and bottom-up suppression in posterior parietal cortex Philosophical Transactions of the Royal Society of London B, 2013; 368(1628): 20130069.
Wottawa C.R., Cohen J.R., Fan R.E., Bisley J.W., Culjat M.O., Grundfest W.S., Dutson E.P. The role of tactile feedback in grip force during laparoscopic training tasks Surgical Endoscopy, 2013; 27(4): 1111-8.
Shariat Torbaghan S., Yazdi D., Mirpour K., Bisley J.W. Inhibition of return in a visual foraging task in non-human subjects Vision Research, 2012; 74(4): 2-9.
Mirpour K., Bisley J.W. Anticipatory remapping of attentional priority across the entire visual field The Journal of Neuroscience, 2012; 32(46): 16449-57.
Mirpour K., Bisley J.W. Dissociating activity in the lateral intraparietal area from value using a visual foraging task Proceedings of the National Academy of Sciences of the United States of America, 2012; 109(25): 10083-8.
Arcizet F., Mirpour K., Bisley J.W. A pure salience response in posterior parietal cortex Cerebral Cortex, 2011; 21(11): 2498-506.
Ong W.S., Bisley J.W. A lack of anticipatory remapping of retinotopic receptive fields in the middle temporal area J Neurosci, 2011; 31(29): 10432-6.
Bisley J.W., Mirpour K., Arcizet F., Ong W.S. The role of the lateral intraparietal area in orienting attention and its implications for visual search Euro J Neurosci, 2011; 33(11): 1982-90.
Bisley J.W. The neural basis of visual attention J Physiol, 2011; 589(Pt 1): 49-57.
Bisley J.W., Goldberg M.E. Attention, intention, and priority in the parietal lobe Ann Rev Neurosci, 2010; 33(6): 1-21.
Mirpour K., Ong W.S., Bisley J.W. Microstimulation of posterior parietal cortex biases the selection of eye movement goals during search J Neurophysiol, 2010; 104(6): 3021-8.
Culjat M.O., Bisley J.W., King C.-H., Wottawa C., Fan R.E., Dutson E.P., Grundfest W.S. Tactile feedback in surgical robotics, Surgical Robotics – Systems, Applications and Visions, 2010; 449-468.
Mirpour K., Arcizet F., Ong W.S., Bisley J.W. Been there, seen that: a neural mechanism for performing efficient visual search J Neurophysiol, 2009; 102(6): 3481-91.
Ong W.S., Hooshvar N., Zhang M., Bisley J.W. Psychophysical evidence for spatiotopic processing in area MT in a short-term memory for motion task J Neurophysiol, 2009; 102(4): 2435-40.
King C.-H., Culjat M.O., Franco M., Lewis C.E., Dutson E.P., Grundfest W.S., Bisley J.W. Tactile feedback induces reduced grasping force in robot-assisted surgery, IEEE Trans Haptics , 2009; 2: 103-110.
Bisley J.W., Ipata A.E., Krishna B.S., Gee A.L., Goldberg M.E. The lateral intraparietal area: a priority map in posterior parietal cortex, Cortical Mechanisms of Vision, 2009; 9-34.
Ipata A.E., Gee A.L., Bisley J.W., Goldberg M.E. Neurons in the lateral intraparietal area create a priority map by the combination of disparate signals Exp Brain Res, 2009; 192(3): 479-88.
King C.-H., Culjat M.O., Franco M.L., Bisley J.W., Dutson E., Grundfest W.S. Optimization of a pneumatic balloon tactile display for robot-assisted surgery based on human perception IEEE Trans Biomed Eng, 2008; 55(11): 2593-600.
Gee A.L., Ipata A.E., Gottlieb J., Bisley J.W., Goldberg M.E. Neural enhancement and pre-emptive perception: the genesis of attention and the attentional maintenance of the cortical salience map Perception, 2008; 37(3): 389-400.
Fan R.E., Culjat M.O., King C.-H., Franco M.L., Boryk R., Bisley J.W., Dutson E., Grundfest W.S. A haptic feedback system for lower-limb prostheses IEEE Trans Neural Syst Rehabil Eng, 2008; 16(3): 270-7.
Ganguli S., Bisley J.W., Roitman J.D., Shadlen M.N., Goldberg M.E., Miller K.D. One-dimensional dynamics of attention and decision making in LIP Neuron, 2008; 58(1): 15-25.
Gee A.L., Ipata A.E., Bisley J.W., Gottlieb J., Goldberg M.E. On the agnosticism of spikes: salience, saccades, and attention in the lateral intraparietal area of the monkey, Sensorimotor Foundations of Higher Cognition: Attention and Performance XXII, 2007; 3-25.
Ipata A.E., Gee A.L., Goldberg M.E., Bisley J.W. Activity in the lateral intraparietal area predicts the goal and latency of saccades in a free viewing visual search task J. Neurosci, 2006; 26(14): 3656-3661.
Ipata A.E., Gee A.L., Gottlieb J., Bisley J.W., Goldberg M.E. LIP responses to a popout stimulus are reduced if it is overtly ignored Nat Neurosci, 2006; 9(8): 1071-1076.
Bisley J.W., Goldberg M.E. Neural correlates of attention and distractibility in the lateral intraparietal area J Neurophysiol, 2006; 95(3): 1696-717.
Goldberg M.E., Bisley J.W., Powell K.D., Gottlieb J. Saccades, salience and attention: the role of the lateral intraparietal area in visual behavior Prog Brain Res, 2006; 155: 157-175.
Bisley J.W., Zaksas D., Droll J.A., Pasternak T. Activity of neurons in cortical area MT during a memory for motion task J Neurophysiol, 2004; 91(1): 286-300.
Bisley J.W., Krishna B.S., Goldberg M.E. A rapid and precise on-response in posterior parietal cortex J Neurosci, 2004; 24(8): 1833-8.
Bisley J.W., Goldberg M.E. The role of the parietal cortex in the neural processing of saccadic eye movements Adv Neurol, 2003; 93: 141-57.
Pasternak T., Bisley J.W., Calkins D. Visual information processing in the primate brain, Biological Psychology, 2003; 139-185.
Bisley J.W., Goldberg M.E. Neuronal activity in the lateral intraparietal area and spatial attention Science, 2003; 299(5603): 81-6.
Bisley J.W., Zaksas D., Pasternak T. Microstimulation of cortical area MT affects performance on a visual working memory task J Neurophysiol, 2001; 85(1): 187-96.
Zaksas D., Bisley J.W., Pasternak T. Motion information is spatially localized in a visual working-memory task J Neurophysiol, 2001; 86(2): 912-21.
Bisley J.W., Goodwin A.W., Wheat H.E. Slowly adapting type I afferents from the sides and end of the finger respond to stimuli on the center of the fingerpad J Neurophysiol, 2000; 84(1): 57-64.
Bisley J.W., Pasternak T. The multiple roles of visual cortical areas MT/MST in remembering the direction of visual motion Cereb Cortex, 2000; 10(11): 1053-65.
Goodwin A.W., Macefield V.G., Bisley J.W. Encoding of object curvature by tactile afferents from human fingers J Neurophysiol, 1997; 78(6): 2881-8.
Bisley J.W., Rees S.M., McKinley M.J., Hards D.K., Oldfield B.J. Identification of osmoresponsive neurons in the forebrain of the rat: a Fos study at the ultrastructural level Brain Res, 1996; 720(1-2): 25-34.

Felix Schweizer Ph.D.

Academic Titles/Accomplishments/Affiliations:

Director, Neurosciences Interdepartmental Program
Vice-Chair for Education, Department of Neurobiology
Member, Neuroscience GPB Home Area
Collaborator, Vestibular Neuroscience Laboratory
Member, Brain Research Institute
Cell & Developmental Biology GPB Home Area
Molecular, Cellular & Integrative Physiology GPB Home Area

Felix E. Schweizer was born in Basel, Switzerland and conducted his graduate research in the laboratory of Prof. Max M. Burger under the direction of Dr. Theo Schafer. He received his PhD degree in biochemistry summa cum laude from the University of Basel in 1989. From 1990 to 1994, he was a post-doctoral fellow in the Department of Molecular and Cellular Physiology at Stanford University in the laboratory of Prof. Richard W. Tsien. From 1994 to 1998, he was postdoctoral fellow in the Department of Neurobiology at Duke University in the laboratory of Professor George J. Augustine. Dr. Schweizer joined the Department of Neurobiology in the David Geffen School of Medicine at UCLA in 1998 as Assistant Professor and was promoted to Full Professor in 2010. Dr. Schweizer’s research interests concern the molecular mechanisms by which neurons communicate, the regulation of communication by neurons and how alterations in neuronal communication might contribute to neuronal diseases. The Schweizer laboratory uses electrophysiological and optical tools to investigate the dynamic molecular mechanisms underlying the regulation of neurotransmitter release. We are particularly interested in the role of protein ubiquitination in regulating neuronal excitability and synaptic transmission. In collaboration with Dr. James Wohlschlegel, we used multiplexed SILAC and identified synaptic proteins that are dynamically regulated. We are now in the process to test the role of individual proteins in cultured neurons, brain slices and, in collaboration with Dr. David Krantz, in Drosophila. In addition, we are characterizing transmission at the first synapse of the vestibular system, i.e. between utricular sensory hair cells and primary afferent neurons. In collaboration with Dr. Larry Hoffman we are finding that changing the gravitational load alters synaptic structures. We are now using serial EM and EM tomography in addition to physiology and cell biology to define in more detail the transfer function between head-movement input and afferent nerve-firing output.

Paul E Micevych Ph.D.

Research interest:
The research of the laboratory is focused on steroid hormone interactions with the central nervous system. Throughout life, sex steroid hormones profoundly influence the structure and function of specific circuits that regulate reproduction and reproductive behaviors. Previous work had focused on the regulation of neuropeptide and transmitter expression. However, relatively little is known about the mechanisms by which steroids affect postsynaptic activation and signal transduction. The laboratory has three major interests: STEROID MODULATION OF mu-OPIOID RECEPTOR (MOR) ACTIVATION Estrogen treatment of ovariectomized rats initially has an inhibitory action on circuits mediating sexual receptivity (lordosis), but eventually induces sexual receptivity. We have determined that an important component of this inhibition is due to the activation of MOR circuits in the medial preoptic area. Taking advantage of G protein-coupled receptor (GPCR) internalization following activation of the receptor by an endogenous ligand, we determined that activation of MOR is correlated with an inhibition of lordosis. Behaviorally, progesterone augments estrogen action. We have determined that progesterone relieves MOR-mediated inhibition, through the termination of opioid release in the medial preoptic area. Is the MOR-inhibition dependent on estrogen receptors? Working with Dr. Emilie Rissman, (University of Virginia), we have determined that estrogen activation of MOR circuits is dependent on the expression of the estrogen receptor-a (ERa). Although MOR and opioid expression appears nominal in ERa knockout (ERaKO) mice, and MOR-selective opioids internalize MOR, estrogen does not induce internalization. These results and the rapid time course of internalization suggest that the ERa is acting through a nongenomic mechanism. REGULATION OF NEUROSTEROID BIOSYNTHESIS Although it is well known that the brain can synthesize neurosteroids, it has been difficult to determine the function of these steroids in the regulation of reproduction. We have recently determined that peripheral estrogen stimulates the synthesis of progesterone in the hypothalamus. This increased in progesterone is restricted to the hypothalamus and is necessary for the initiation of the LH surge. Examination of cells in vitro suggest that astrocytes are responsible for the estrogen-induced progesterone synthesis. This response to estrogen may be an important component of estrogen positive feedback regulates the LH surge. Males and aging females that do not exhibit positive feedback, that are lacking the ability to increase progesterone synthesis in the hypothalamus. NONGENOMIC ACTIONS OF ESTROGEN MODULATION To begin examining the nongenomic actions of estrogen on regulation of postsynaptic mechanisms, we have studied the response of Ca2+ in dorsal root ganglion (DRG) cells. DRG cells provide an accessible and practical solution to quantitatively study the chemosensitive properties of estrogen-sensitive neurons. These cells express ERa and a number of other well characterized Ca2+ channels. We have been studying the effects of estrogen on modulation of P2X receptors (ATP receptors) and activity of voltage dependent Ca2+ channels (VdCC) using digital videomicroscopy for [Ca2+]i changes. Recent results indicate that 17-beta estradiol inhibited ATP-mediated [Ca2+]i responses and attenuated Ca2+ rise by acting on L-type VDCC in both male and female DRG neurons

The reproductive hormones estradiol and progesterone bathe our internal organs. They have profound influence over the central and peripheral nervous system. While these steroids have been studied for many years, recent advances indicate that many actions of estradiol in the nervous system are mediated by receptors located on the cell membrane, suggesting more of a neurotransmitter than a hormonal role. My lab is working to understand the multiple mechanisms and circuits through which estrogen and progesterone affect cell types in different systems to affect reproduction, behavior, pain transmission and neuroprotection.