SYNAPTIC TRANSMISSION IN THE CNS

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The past 20 years has seen a remarkable increase in our knowledge of cellular and molecular properties of the nervous system, but how these properties are combined into functional circuits remains a daunting challenge. Small synaptic circuits represent the functional modules that underlie information processing in the brain. Disruption of circuits is central to diseases ranging from mental retardation, autism and schizophrenia to traumatic brain injury, epilepsy and Alzheimer s disease. These modules share many common features in different brain systems, yet our knowledge of their functional organization at the cellular level remains rudimentary. Sensory systems provide an attractive experimental system for such questions because their modular organization is amenable to direct study, e.g. barrels in the somatosensory cortex. In this project, we will use the olfactory bulb as a model to address how circuits process information. The olfactory system is attractive for this purpose because of the elegant spatial mapping of sensory input and its relatively simple circuitry. While theories of olfactory function abound, based largely on macroscopic recording or molecular maps, information is lacking at the cellular level to match functions, e.g. signal amplification or discrimination, with elements in the chain from receptor neuron to olfactory bulb to olfactory cortex. This is a problem of synaptic integration, involving the strength and duration of individual synaptic responses; the connectivity of synapses within the network; and the excitable properties of neurons. We hypothesize that fast and slow synchronization of cellular activity in the glomerular layer are required for high fidelity coding of sensory information while interneuronal networks within the bulb (periglomerular and granule cells) play a role in discrimination, but not in the traditional sense of lateral inhibition. The principal cells, mitral cells, receive input from only one glomerulus, thus comparison of mitral cells within the same or different glomeruli provide a powerful in vitro approach to circuit analysis. We will use paired recording from cells in rodent brain slices, guided by use of cell-specific genetically-labeled mice, to manipulate assess the cellular properties and organization modules that determine information processing in this circuit. Our preliminary data provide strong clues to the role of rapid signaling by gap junctions as well as slow synaptic signaling mechanisms. These data also provide hypotheses about behavior that we will directly test. These studies are expected to provide important insights into synaptic integration in the olfactory bulb as well as for other brain circuits.