Project Summary/Abstract Mirror neurons constitute a distinct class of neurons in that their firing rates are modulated both during performance and during observation. We will investigate three aspects of mirror neuron physiology. First, given that mirror neurons are thought to mediate understanding of another individual’s actions, in Aim 1 we ask if mirror neuron activity during observation differs depending on whether or not the individual performing the movement is of the same species. We hypothesize H1A – that mirror neuron activity is modulated more when the observing subject watches an individual from the same species than when the performer is from a different species. Furthermore, we hypothesize H1B – that communication between a conspecific performer and observer enhances observation-related activity. Second, although most studies of mirror neurons have focused on modulation during movement per se, our preliminary studies suggest that mirror neuron populations represent entire sequences of multiple behavioral epochs, including epochs during which no movement occurs. In Aim 2 we ask whether mirror neuron populations represent behavioral epochs other than the movement per se. We hypothesize: H2A – that mirror neurons are modulated during separate instruction and/or preparatory periods; H2B – that mirror neuron populations represent entire sequences of multiple behavioral epochs whether the subject is performing or observing; and H2C – that the representation of behavioral epoch sequences is similar during performance and observation in mirror neuron populations from the ventral or dorsal premotor cortex, but different in those from the primary motor cortex. Third, we introduce the novel notion that i) condition-dependent modulation of mirror neuron activity related to the location to which the arm must reach and to the object the hand must grasp is dissociable experimentally from ii) condition-independent modulation that represents the sequence of behavioral epochs. In Aim 3 we ask whether inactivation of the parietal reach region (PRR) and/or the anterior intraparietal area (AIP) reduces or eliminates condition-dependent information in the premotor and motor cortex, while leaving condition- independent modulation relatively unchanged. We hypothesize: H3A – that during observation, inactivation of PRR and/or AIP will reduce or eliminate the location- and/or object-related modulation, respectively, of mirror neuron populations, H3B – while leaving the condition-independent modulation relatively unchanged.