In mammals, the dorsomedial striatum is one brain area shown to be critical for the flexible shifting of response patterns. At present, the neurochemical mechanisms that underlie learning during a shift in response patterns are unknown. The present study examined the effects of NMDA competitive antagonist, dl-2-amino-5-phosphonopentanoic acid (AP-5), injected into the dorsomedial striatum on the acquisition and reversal of a response discrimination. Male Long-Evans rats were tested across two consecutive days in a modified cross-maze. Rats received an infusion of either saline or AP-5 (5 or 25 nmol) 5 min prior to each test session. In the acquisition phase rats learned to turn in one direction (right or left) to receive a cereal reinforcement. In the reversal learning phase rats learned to turn in the opposite direction as in the acquisition phase. In both phases, criterion was achieved when a rat made 10 consecutive correct trials. Infusions of AP-5 did not impair acquisition, but impaired reversal learning of a response discrimination in a dose-dependent fashion. The reversal learning deficit induced by AP-5 resulted from reversions back to the originally learned response pattern following the initial shift. These results suggest that activation of NMDA receptors in the dorsomedial striatum are critical for the flexible shifting of response patterns by enhancing the reliable execution of a new response pattern under changing task contingencies.
One idea about the role of the striatum in learning and memory is that it has a unitary function supporting the acquisition of stimulus–response associations or “egocentric” response learning (Colombo, Davis, & Volpe, 1989; Cook & Kesner, 1988; Kesner, Bolland, & Dakis, 1993; Knowlton, Mangels, & Squire, 1996; McDonald & White, 1993; Mishkin, Malamut, & Bachevalier, 1984; Packard, Hirsh, & White, 1989; Packard & McGaugh, 1992; Potegal, 1969; Potegal, Copack, de Jung, Krauthamer, & Gilman, 1971). More recent studies indicate that the dorsolateral striatum, in particular, may be an area critical for the learning of arbitrary stimulus–response associations (Devan, McDonald, & White, 1999; Featherstone and McDonald, 2004a and Featherstone and McDonald, 2004b; Jog, Kubota, Connolly, Hillegaart, & Graybiel, 1999; Packard & McGaugh, 1996; Packard, 1999; Reading, Dunnet, & Robbins, 1991; White & McDonald, 2001; Yin, Knowlton, & Balleine, 2004). For example, rats with dorsolateral striatal lesions are impaired in learning a conditional discrimination, which requires associating a specific visual or auditory stimulus with a particular lever press response (Featherstone and McDonald, 2004a and Featherstone and McDonald, 2004b; Reading et al., 1991). Furthermore, recording from neurons in the rat dorsolateral striatum during the acquisition of a tone–response conditional discrimination indicate this area is critical for learning of stimulus–response associations (Jog et al., 1999). As performance improved in acquisition of the tone–response discrimination there was a concomitant increase in the percentage of neurons that showed correlated firing to a particular aspect of the task, e.g., initiation of movement or tone presentation. In addition, this selective activation of dorsolateral striatal neurons to different aspects of the learned stimulus–response association remained stable for weeks (Jog et al., 1999). Thus, findings from recording of dorsolateral striatal neurons and lesions of this area suggest that the dorsolateral striatum may be crucial for stimulus–response learning.
