Nicholas Brecha

Nicholas C Brecha

Professor, Neurobiology, University of California Los Angeles

Professor, Medicine, University of California Los Angeles

Professor, Ophthalmology, University of California Los Angeles

310-825-9556

73-244 CHS
Los Angeles, CA 90095

Lab Number:
310-825-6758

Research Interests

My research interests are concerned with understanding the functional organization, and regulation of fast (amino acid) and slow (peptide) transmitter systems to better understand cell – cell communication in the nervous system. Investigations have mainly used the retina as a model to evaluate these transmitter systems. In particular, my research interests are focused on evaluating the morphological and neurochemical organization of the inner retina, and amacrine and bipolar 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 and opiate peptide receptors. These 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. Significant efforts are also focused on the identification and characterization of GABAergic cell types and their sites of action in the retina with specific antibodies to GABA, to the GABA synthetic enzymes, and to individual subunits of the GABAA receptor complex. Finally, to determine the sites of synaptic inactivation of GABA, the cellular localization of GABA uptake sites is being determined using novel cDNA probes and antibodies to the GABA plasma membrane transporters, GAT-1, GAT-2, GAT-3 and BGT. Overall, these studies have demonstrated the presence of distinct neurochemically identified bipolar, amacrine and ganglion cell populations. These observations indicate that different amacrine, bipolar and ganglion cell populations form defined retinal microcircuits, and play unique roles in the processing of visual information.
 

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.

Publications

A selected list of publications: