Thus, this study aimed E7080 in vitro to test the hypothesis that controlled lesions of the monkey PRR would produce

OA-like symptoms, deficits specifically in reaching to peripheral targets but not reaching to central targets or saccades. To test this hypothesis, we investigated how PRR inactivation affects goal-directed movements in two macaque monkeys (Y and G). We alternated between inactivation and control sessions spaced at least 24 hr apart (15 inactivation sessions in total for monkey Y and 19 for monkey G) (Experimental Procedures and see Table S1 available online). Because unilateral lesions are sufficient to cause OA in human patients, we inactivated only the right hemisphere in monkey Y and the left hemisphere in monkey G (Perenin and Vighetto, 1988). Both monkeys used the arm opposite to the inactivated hemisphere for reaching. In the beginning of each inactivation session, we injected typically 5 μl of muscimol, a GABAA agonist that suppresses local neuronal activity, through an acutely inserted cannula (Martin and Ghez, 1999). The inactivation cannula was inserted at an almost constant location where we previously recorded a large number of neurons satisfying the functional criteria of PRR that firing rate is more strongly tuned to reach goal

direction than to saccade direction (Figure 1A) (Snyder et al., 1997). We visualized the inactivated area through MRI after injecting the MRI-visible contrast agent gadolinium, Selleck Metabolism inhibitor known to faithfully reflect the spread of muscimol (Heiss et al., 2010). As indicated by the gadolinium

spread, our inactivation was contained within a small volume in the medial wall of IPS, a part of PRR (Figures 1B and 1C). Anatomically, the inactivated area may overlap with the medial intraparietal area (MIP) and/or the ventral part of area 5 (5v). Because of this ambiguity, we hereafter refer to the inactivated area simply as “PRR. The functional properties of PRR neurons, if causal, predict that PRR inactivation would distort the intended reach goals, which in turn would affect of reach endpoint locations. Moreover, the effect would be selective for reaching movements. To test these predictions, we first compared the effects of PRR inactivation on reach and saccade endpoints in memory-guided reach and saccade tasks (seven controls and six inactivations for monkey Y, six and six for monkey G; Figure 2A). Figure 2B displays the reach and saccade endpoints from representative inactivation and control sessions. In comparison to the control session, reaches in the inactivation session ended short of the targets, i.e., reaches were hypometric for several target locations (see Figure S1A for trajectory information). In contrast, the inactivation saccade endpoints were not noticeably different from the control saccade endpoints.