Habituation, a simple form of nonassociative memory, is a common feature of sensory systems and is characterized as a decrease in responsiveness to repeated stimuli. Sensory habituation allows filtering of less significant, or predictable events than other mechanisms such as receptor adaptation. Disorders of sensory filtering have been implicated in disease states such as autism. The present proposal examines mechanisms of olfactory habituation in the anterior piriform cortex (aPCX). The aPCX is an ideal model system to study habituation because of its relatively simple and well described synaptic organization, and the extensive knowledge of its synaptic physiology. Preliminary results demonstrate that aPCX neurons habituate more rapidly than simultaneously recorded afferent activity from the main olfactory bulb, and that this habituation is associated with a decrease in afferent synaptic efficacy. The proposed work is divided into four basic experiments. The first will further describe odor habituation in the aPCX and main olfactory bulb, with particular attention paid to characterizing its time course and odor specificity. Specific responses will be correlated with cell morphology and location by intracellular filling and imaging of recorded cells. The second experiment will further examine synaptic correlates of odor habituation by measuring the efficacy of identified synapses within the aPCX. (This aim has already been partially met by results obtained since the application was submitted, that indicate that there is a decrease in synaptic afferents with odor habituation.) The third and fourth experiments will test specific hypotheses of odor response plasticity with a combination of intracellular recording and pharmacological manipulations. The third is specifically aimed at the role of decreased excitation in odor habituation, particularly LTD mediated through NMDA receptors. The fourth will examine the role of increased inhibition in habituation, produced through either GABAA or GABAB receptors. Together, it is hoped that these studies will provide important information into both the mechanisms of habituation and synaptic mechanisms of information processing in the olfactory system.