The mammalian olfactory system is unique among sensory systems in its dense interconnectivity with the limbic system, which has been shown to be involved in processes such as memory, emotion and spatial and other types of cognitive processes. It is therefore important to understand the olfactory system's role in attentional processes as they relate to the changing demands of an individual's environment. These processes are significantly impacted in Alzheimer's and Parkinson's diseases and in schizophrenia and depression (among others), all of which are accompanied by mild to severe olfactory deficits. Recent studies in our laboratories and in others have implicated oscillatory synchrony in attention and sensory processing. We therefore propose multi-disciplinary research aimed at describing the functional role of oscillatory neural synchrony in perception, attention and learning of sensory information in mammalian cortex. The olfactory system is used to study the sensory cortical circuit, the olfactory bulb (OB) and piriform cortex (PC). We emphasize the bidirectional connectivity of these two structures, which few studies have done. Oscillations occur at the level of neural populations, and activity will be studied at this and the single neuron levels in rats performing olfactory discrimination and attention tasks. We use waking animals because many types of oscillatory activity are seen only in alert and attentive states, and these unique oscillations provide a tool by which to investigate the biophysical basis, behavioral dependence and interactions of these oscillations. An advantage of using the olfactory system lies in the breadth of physiological, anatomical and modeling efforts that have addressed this system at many levels of analysis, from single neuron biophysics to neural populations.

These studies aim to 1) describe the sources of several types of oscillatory activity associated with sensory processing and attention in waking rats; 2) describe how these types of oscillations change with learning and context; and 3) manipulate inhibitory action in the underlying circuits pharmacologically, relating these manipulations to changes in olfactory discrimination. Each portion of the physiological studies are closely coupled with computational modeling, acting in both a descriptive and predictive fashion.

Detailed analysis of this system in waking animals will provide a foundation from which to understand the complex system effects in cognitive disorders. We anticipate that understanding how olfactory deficits arise from changes in the limbic system associated with many of these disorders, will help us to understand the mechanisms that produce cognitive malfunctioning.

R01DC007995

2005-08-01

2010-07-31