In the mammalian brain, early sensory areas are organized as stereotyped maps of stimulus qualities. The anatomical features of these sensory maps underlie the neuronal computations and information processing that are essential to generate appropriate perceptual experiences and behaviors. In the mammalian olfactory bulb (OB), the most striking anatomical feature of this sensory map is the convergent axonal input from primary olfactory sensory neurons (OSNs); specifically, each insular glomerular structure in the OB receives axons exclusively from OSNs expressing the same odorant receptor. Moreover, OB projection neurons, the mitral/tufted cells, also project their primary dendrites exclusively into a single glomerulus. However, it is not well understood how this strict pattern of convergence and segregation contributes materially to the processing of olfactory information and odor-driven behaviors. In this project, we establish a multi-disciplinary approach to determine the contribution of this strict anatomical mapping to odor representation and perception. Specifically, we will genetically manipulate the projection patterns of OSN populations to perturb the anatomical map in the olfactory bulb, and perform a battery of automated behavioral assays probing odor discrimination and recognition. We then will integrate mathematical models based on OB circuitry with electrophysiological and optical imaging studies to elucidate the basis for these response differences in wildtype and mutant mice. By combining genetics, behavior, electrophysiological, and imaging approaches, we will determine the impact of genetically altered glomerular maps on odor perception under both nave and learned conditions.
Precise neuronal connectivity in the nervous system is essential for its proper function. Cognitive deficits in many psychiatric disorders arise from disruptions in neural connectivity, including disruptions within sensory circuits. The proposed study investigates the role of a specialized, anatomical neuronal connectivity pattern in regulating sensory information processing and perceptual experience. Results from this study will reveal how brain function can deteriorate because of disruptions in the normal connection patterns among neurons.
| Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano et al. (2018) Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation. Neuron 97:1137-1152.e5 |
| Tong, Michelle T; Kim, Tae-Young P; Cleland, Thomas A (2018) Kinase activity in the olfactory bulb is required for odor memory consolidation. Learn Mem 25:198-205 |
| Li, Guoshi; Cleland, Thomas A (2017) A coupled-oscillator model of olfactory bulb gamma oscillations. PLoS Comput Biol 13:e1005760 |
| McIntyre, Alexa B R; Cleland, Thomas A (2016) Biophysical constraints on lateral inhibition in the olfactory bulb. J Neurophysiol 115:2937-49 |
