6-Hydroxydopamine Lesions in the Rat Neostriatum Impair Sequential Learning in a Serial Reaction Time Task

Abstract

Sequential behavior has been intensively investigated in humans using so-called serial reaction time tasks(SRTT), in which visual stimuli are either presented in a random or sequential order. Typically, when the stimulus presentation follows a previously learned sequential order,reaction times are decreased compared to random stimulus presentation and become partly automated. A vast amount of SRTT findings indicates that sequential learning and performance seem to be mediated amongst others by the basal ganglia-especially the striatum-and the neurotransmitter dopamine therein. In this study we used an operant rat version of the human four choice SRTT to investigate the effect of bilateral neostriatal dopamine lesions induced by 6-hydroxydopamine on sequential learning. The rats' task was to respond rapidly to illuminated holes by nose-poking into them. During extensive training, the position of the illuminated hole followed a 12-item sequence. The outcome of this sequential training was also investigated in two tests, namely an interference test, where stimulus presentation switched between this sequential and a pseudo random order every five minutes, and a violation test, in which only one sequence item was eventually skipped. The neurotoxic lesions, which was placed before the start of training, led to the expected sub-total dopamine depletions (i.e. residual levels around 34-56% of controls), especially in the medial neostriatum. These lesions did not lead to general motor deficits in a catalepsy task, but moderate deficits in locomotion in an activity box, which largely recovered with time after lesion. In the SRTT, rats with lesions showed impaired learning, that is, less response accuracy and slower reaction times than the control group.During a subsequent test with alternating phases of sequential and random stimulus presentations, reaction times and accuracy of the control group were superior during sequential as compared to random stimulus phases. In the lesion group, only a moderate advantage in accuracy was observed. In the violation test, another outcome measure, the control group showed an expected increase in reaction times on the violated positions. By contrast, the lesion group showed no such increase, which indicates less automation of sequential behavior in these animals. For one, these findings support previous evidence in showing that neostriatal dopamine plays an important role for instrumental behavior, in general. Furthermore,and most importantly, they suggest that dopaminergic-striatal networks also play an important role in sequential behavior, especially its acquisition.

Dorsal hippocampal lesions boost performance in the rat sequential reaction time task

“…Referring to a previous experiment which revealed that sequential learning as assessed by our rat SRTT is severely affected by dopaminergic lesions in the neostriatum (Eckart et al, 2010a), our results strongly support the hypotheses of a possible interference between striatum and hippocampus in some test situations, as previously proposed by and Packard and Knowlton (2002). Both models assume that interference between both structures may occur during striatal stimulus-response learning and hippocampal spatial learning.…”

“…In case of omissions and incorrect pokes, feedback was provided by a tone and illumination of the house light. Then, stimulus presentation continued from that item, where the sequence had been interrupted (Eckart et al, 2010a). Schematic design for the object place recognition test.…”

“…The underlying rationale is that the overall F-value does not seem to be required in order to conduct multiple comparisons where appropriate t-tests are conducted (Wilcox, 1987, Howell, 2002, Eckart et al, 2010a.…”

Dopaminergic Contributions to Vocal Learning

“…8c-f ). Although the caveats detailed above prevent us from drawing strong conclusions about DA's role in vocal learning other than that driven by white noise, future studies could ask whether DA is necessary for error-corrective learning by providing a correctable auditory perturbation to baseline song without explicit external reinforcement (Sober and Brainard, 2009;Hoffmann et al, 2012). Prior studies have identified potential mechanisms by which dopaminergic inputs to area X might mediate vocal learning.…”

“…As in a number of forms of mammalian behavioral plasticity (Ogura et al, 2005;Eckart et al, 2010), the basal ganglia are crucial for vocal plasticity in songbirds. Area X (Fig.…”