The long term goal of this project is to understand the neural basis of cortical function. We study the olfactory pathway, which consists of simple cortical structures processing a well-defined input, the information carried by odor molecules. Recent evidence is converging on a set of mechanisms underlying odor discrimination, which we will test in this grant. The initial interaction between odor molecules and odor receptors in the olfactory receptor neurons will be analyzed using patch recordings and Ca2+ imaging of cells isolated from parts of the olfactory epithelium that show heightened odor sensitivities, in both salamanders and rodents. Homologous series of odor compounds will be tested, and blockers of related neurotransmitter receptors will be used to dissect the responses pharmacologically. At the first stage Of synaptic processing, we will analyze the mapping of odor responses in the olfactory glomeruli using the voltage-sensitive dyes. This should further test the hypothesis that odor molecular structures are encoded as """"""""odor images"""""""" in the glomeruli. in the olfactory bulb, mechanisms underlying synaptic processing of odor information will be analyzed using in vitro slices and cultured cells of rodents. Critical hypotheses will be tested regarding the roles of metabotropic glutamate receptors, GABAergic inhibitory mechanisms, and the cGMP/cyclic nucleotide gated channel system, in sensory processing and olfactory memory. The results should add to a growing consensus on the molecular and neural mechanisms underlying the sense of smell. This will provide a better scientific basis for understanding normal smell perception as well as disorders of smell perception and memory in neurological disease.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Schools of Medicine
New Haven
United States
Zip Code
Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798
Faridi, R; Rehman, A U; Morell, R J et al. (2017) Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome. Clin Genet 91:328-332
Chattaraj, Parna; Munjal, Tina; Honda, Keiji et al. (2017) A common SLC26A4-linked haplotype underlying non-syndromic hearing loss with enlargement of the vestibular aqueduct. J Med Genet 54:665-673
Honda, Keiji; Kim, Sung Huhn; Kelly, Michael C et al. (2017) Molecular architecture underlying fluid absorption by the developing inner ear. Elife 6:
Naz, Sadaf; Imtiaz, Ayesha; Mujtaba, Ghulam et al. (2017) Genetic causes of moderate to severe hearing loss point to modifiers. Clin Genet 91:589-598
Hamilton, David J; Shepherd, Gordon M; Martone, Maryann E et al. (2012) An ontological approach to describing neurons and their relationships. Front Neuroinform 6:15
Phillips, Matthew; Boman, Erik; Osterman, Hanna et al. (2011) Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice--a longitudinal study. PLoS One 6:e19567
Shepherd, Gordon M; Greer, Charles A; Mazzarello, Paolo et al. (2011) The first images of nerve cells: Golgi on the olfactory bulb 1875. Brain Res Rev 66:92-105
Morse, Thomas M; Carnevale, Nicholas T; Mutalik, Pradeep G et al. (2010) Abnormal Excitability of Oblique Dendrites Implicated in Early Alzheimer's: A Computational Study. Front Neural Circuits 4:
Shepherd, Gordon M (2009) Symposium overview and historical perspective: dendrodendritic synapses: past, present, and future. Ann N Y Acad Sci 1170:215-23

Showing the most recent 10 out of 20 publications