Short-latency activation of striatal spiny neurons via subcortical visual pathways.

The striatum is a site of integration of neural pathways involved in reinforcement learning. Traditionally, inputs from cerebral cortex are thought to be reinforced by dopaminergic afferents signaling the occurrence of biologically salient sensory events. Here, we detail an alternative route for short-latency sensory-evoked input to the striatum requiring neither dopamine nor the cortex. Using intracellular recording techniques, we measured subthreshold inputs to spiny projection neurons (SPNs) in urethane-anesthetized rats. Contralateral whole-field light flashes evoked weak membrane potential responses in approximately two-thirds of neurons. However, after local disinhibitory injections of the GABA(A) antagonist bicuculline into the deep layers of the superior colliculus (SC), but not the overlying visual cortex, strong, light-evoked, depolarizations to the up state emerged at short latency (115 +/- 14 ms) in all neurons tested. Dopamine depletion using alpha-methyl-para-tyrosine had no detectable effect on striatal visual responses during SC disinhibition. In contrast, local inhibitory injections of GABA agonists, muscimol and baclofen, into the parafascicular nucleus of the thalamus blocked the early, visual-evoked up-state transitions in SPNs. Comparable muscimol-induced inhibition of the visual cortex failed to suppress the visual responsiveness of SPNs induced by SC disinhibition. Together, these results suggest that short-latency, preattentive visual input can reach the striatum not only via the tecto-nigro-striatal route but also through tecto-thalamo-striatal projections. Thus, after the onset of a biologically significant visual event, closely timed short-latency thalamostriatal (glutamate) and nigrostriatal (dopamine) inputs are likely to converge on striatal SPNs, providing depolarizing and neuromodulator signals necessary for synaptic plasticity mechanisms.

Spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats differ in performance on a win-shift task in the water radial arm maze.

The spontaneously hypertensive rat (SHR) is a commonly used animal model of attention deficit hyperactivity disorder. Previous literature is inconclusive with respect to the exact nature of memory impairments in this strain. The objective of this study was to assess spatial memory as measured by performance of male SHR, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats on a win-shift version of the water radial arm maze. On this task, all strains made more errors on Trial 4 when the mnemonic demand was highest, and showed a similar response when the delay was increased from 60s to 2h on Week 3. Both SHR and WKY rats made more reference memory errors than SD, however, SHR showed minimal improvement over weeks. The increase in errors may be due to a greater inclination of SHR and WKY to use a chaining strategy of entering consecutive arms than SD. Furthermore, the number of incomplete arm entries into reference memory arms decreased over weeks in WKY and SD, but increased in SHR, suggesting increased impulsivity of SHR at the later stages of testing. Although based on number of errors, the data indicate that SHR may have memory deficits, the data relating to arm entries suggest that the minimal improvement in SHR over weeks may have been due to greater impulsivity in the later weeks, rather than defective memory. Thus, these findings are consistent with SHR having impairments with selection of appropriate behavioural responses in a goal-directed task.

Short-term memory impairment and reduced hippocampal c-Fos expression in an animal model of fetal alcohol syndrome.

BACKGROUND: Previous work in our laboratory has shown that exposure to ethanol during the brain growth spurt impairs spatial short-term memory in rats on the delayed matching-to-place (DMP) version of the Morris water maze. The objectives of this study were to ascertain whether this impairment could: 1) be prevented by increasing the length of encoding time and 2) be related to hippocampal c-Fos expression. METHODS: Using an artificial rearing model, male Long-Evans rats were fed 6.5 g/Kg/day of ethanol from postnatal days 6-9, with controls fed an isocaloric amount of maltose dextrin. As adults, rats in each treatment condition were trained and subsequently tested on either the DMP version of the Morris water maze, or on a random platform version (RAN) that incorporated the same performance requirements, but disallowed spatial learning. Brains were processed for c-Fos expression. RESULTS: Ethanol-exposed rats showed longer search trials during training and took longer to learn the DMP task. When the delay between search and recall trials was increased from 60 sec to 120 min, the performance of ethanol-exposed rats was impaired compared with that of controls after a 10 sec, but not after a 45 sec, encoding time. Brain c-Fos expression was increased in hippocampus, prefrontal cortex and visual cortex in rats trained on the DMP compared to the RAN task. Furthermore, in the DMP-trained rats, hippocampal c-Fos expression was lower in ethanol-exposed rats. CONCLUSIONS: These results suggest that the short-term memory impairment of ethanol-exposed rats 1) can be improved slightly by an increase in encoding time and 2) is related to a decrease in c-Fos expression in the hippocampus.

Spontaneously hypertensive and Wistar Kyoto rats differ in delayed matching-to-place performance and response to dietary long-chain polyunsaturated fatty acids.

Spontaneously hypertensive rats (SHR) were used as an animal model of attention deficit hyperactivity disorder (ADHD). This study investigated whether, in comparison with its progenitor strain, Wistar-Kyoto rats (WKY), SHR would show deficits in spatial short-term memory in the delayed-matching-to-place (DMP) version of the Morris water maze and be more distracted by exposure to a novel stimulus during recall trials. It also addressed whether dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA) during development would increase brain docosahexaenoic acid (DHA) and improve SHR behavioral performance. Beginning at weaning (21 days), male SHR and WKY were fed either a control or LCPUFA supplemented diet [0.5% arachidonic acid (AA) and 0.9% DHA], and behavioral testing began at 8 weeks. The first three tasks comprised a series of problems, each consisting of an initial search trial and subsequent recall trials. The intertrial interval (ITI) between the search and recall trial was either 60 s or 60 min. Surprisingly, in contrast to SHR, WKY did not appear to use a spatial short-term memory strategy to solve the problem. Notwithstanding, the performance of both strains was affected by the delay, such that they showed longer path lengths at the long compared with the short ITI. There was no effect of dietary supplementation on DMP performance. SHR fed the control diet were less responsive to a novel stimulus introduced on the first recall trial than WKY, and this tended to increase with supplementation. Analysis of brain fatty acid composition indicated that supplementation did increase DHA in the phosphatidylethanolamine fraction in WKY; however, in SHR, there was either no change (phosphatidylethanolamine) or paradoxical decreases (phosphatidylcholine and phosphatidyserine/phosphatidylinositol). Further research is needed to determine whether SHR are an appropriate model for studying a possible relationship between dietary LCPUFA and the behavioral symptoms of ADHD.