Task phase-specific involvement of the rat posterior parietal cortex in performance of the TUNL task.

The posterior parietal cortex (PPC) participates in cognitive processes including working memory (WM), sensory evidence accumulation, and perceptually guided decision making. However, surprisingly little work has used temporally precise manipulations to dissect its role in different epochs of behavior taking place over short timespans, such as WM tasks. As a result, a consistent view of the temporally precise role of the PPC in these processes has not been described. In the present study, we investigated the temporally specific role of the PPC in the Trial-Unique, Nonmatching-to-Location (TUNL) task, a touchscreen-based, visuospatial WM task that relies on the PPC. To disrupt PPC activity in a temporally precise manner, we applied mild intracranial electrical stimulation (ICES). We found that intra-PPC ICES (100 µA) significantly impaired accuracy in TUNL without significantly altering response latency. Moreover, we found that the impairment was specific to ICES applied during the delay and test phases of TUNL. Consistent with previous reports showing delay- and choice-specific neuronal activity in the PPC, the results provide evidence that the rat PPC is required for maintaining memory representations of stimuli over a delay period as well as for making successful comparisons and choices between test stimuli. In contrast, the PPC appears not to be critical for initial encoding of sample stimuli. This pattern of results may indicate that early encoding of visual stimuli is independent of the PPC or that the PPC becomes engaged only when visual stimuli are spatially complex or involve memory or decision making.

Dorsal, but not ventral, hippocampal inactivation alters deliberation in rats.

When facing a choice at a decision point in a maze, rats often display hesitations, pauses and reorientations. Such "vicarious trial and error" (VTE) behavior is thought to reflect decision making about which choice option is best, and thus a deliberation process. Although deliberation relies on a wide neural network, the dorsal hippocampus appears to play a prominent role through both its neural activity and its dynamic interplay with other brain areas. In contrast, the involvement of the ventral hippocampus in deliberation is unexplored. Here, we compared directly the effects of dorsal (dHPC) and ventral intermediate (vHPC) hippocampal inactivations induced by intracerebral muscimol injections on VTE behavior as a model of deliberation. To this aim, we analyzed VTE events as rats were required to switch strategy to a new unlearned reward rule. We used a protocol in which task performance in muscimol-injected animals was minimally altered so as to evidence specific effects on VTE behavior. Our results show subtle alterations in VTE behavior following dHPC, but not vHPC, inactivations, therefore suggesting a specific contribution of the dorsal hippocampus to deliberation through its role in prospective evaluation of future actions.

An animal model of disengagement: Temporary inactivation of the superior colliculus impairs attention disengagement in rats.

The orienting attention network is responsible for prioritizing sensory input through overt or covert shifts of attention among targets. The ability to disengage attention is essential for the proper functioning of this network. In addition to its importance for proper orienting, deficits in disengagement have been recently implicated in autism disorders. Despite its importance, the neural mechanisms underlying disengagement processing are still poorly understood. In this study, the involvement of the superior colliculus (SC) in disengagement was investigated in unrestrained rats that had been trained in a two-alternative light-guided spatial choice task. At each trial, the rats had to choose one of two paths, leading either to a large or a small reward, based on 1 (single-cue) or 2 (double-cue) lights. The task consisted of serial trials with single- and/or double-cue lights, and rats could acquire a large reward if the rats chose infrequent lights when infrequent cue lights were presented after preceding frequent cue lights. Experiment 1 included trials with either single- or double-cue lights, and infrequent trials with double-cue lights required both attentional disengagement and shift of attention from preceding frequent single-cue lights, while experiment 2 included only trials with single-cue lights requiring shifts of attention but not attentional disengagement. The results indicated that temporary inactivation of the SC by muscimol injections selectively impaired performance on trials requiring disengagement. No impairment was observed on the other trials, in which attention disengagement was not required. The results provide the first evidence that the SC is necessary for attentional disengagement.

Contributions of the hippocampus and entorhinal cortex to rapid visuomotor learning in rhesus monkeys.

The hippocampus and adjacent structures in the medial temporal lobe are essential for establishing new associative memories. Despite this knowledge, it is not known whether the hippocampus proper is essential for establishing such memories, nor is it known whether adjacent regions like the entorhinal cortex might contribute. To test the contributions of these regions to the formation of new associative memories, we trained rhesus monkeys to rapidly acquire arbitrary visuomotor associations, i.e., associations between visual stimuli and spatially directed actions. We then assessed the effects of reversible inactivations of either the hippocampus (Experiment 1) or entorhinal cortex (Experiment 2) on the within-session rate of learning. For comparison, we also evaluated the effects of the inactivations on performance of problems of the same type that had been well learned prior to any inactivations. We found that inactivation of the entorhinal cortex but not hippocampus produced impairments in acquiring novel arbitrary associations. The impairment did not extend to the familiar, previously established associations. These data indicate that the entorhinal cortex is causally involved in establishing new associations, as opposed to retrieving previously learned associations. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Temporary inactivation of the rodent hippocampus: an evaluation of the current methodology.

Temporary cellular inactivation is a useful and increasingly popular approach in examining brain function. In general the methods allow for fast-acting manipulations that have the advantage of being reversible. However, there is significant variation in detailed procedures across experiments and most authors show very little evidence about the extent or duration of inactivation. Here we investigate a commonly used method of temporarily inactivating the hippocampus in rats. Using immediate early gene activation after electroconvulsive shock we measure the extent of inactivation using different lengths of infusion needles and one vs. two bilateral infusion sites. Our methods allowed us to uncover some possible confounding factors. We suggest specific variations in the procedures which decrease or eliminate these problems. We also investigate the properties of the sodium channel blocker ropivacaine and recommend this drug based on its functional profile and established low level of toxicity.

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning.

While a number of early studies demonstrated that hippocampal damage attenuates the expression of recent, but not remotely trained tasks, an emerging body of evidence has shown that damage to, or inactivation of, the hippocampus often impairs recall across a wide range of training-testing intervals. Collectively, these data suggest that the time course of hippocampal involvement in the storage or recall of previously-acquired memories may differ according to hippocampal subregion and the particular learning task under consideration. The present study examined the contributions of dorsal (DH) and ventral (VH) hippocampus to the expression of previously-acquired trace fear conditioning, a form of Pavlovian conditioning in which the offset of an initially neutral cue or cues and the onset of an aversive stimulus is separated by a temporal (trace) interval. Specifically, either saline or the GABA-A agonist muscimol was infused into DH or VH prior to testing either 1, 7, 28, or 42 days after trace fear conditioning. The results revealed a marked dissociation: pre-testing inactivation of DH failed to impair performance at any time-point, while pre-testing inactivation of VH impaired performance at all time-points. Importantly, pre-testing inactivation of VH had no effect on the performance of previously-acquired delay conditioning, suggesting that the deficits observed in trace conditioning cannot be attributed to a deficit in performance of the freezing response. Collectively, these data suggest that VH, but not DH, remains a neuroanatomical locus critical to the recall or expression of trace fear conditioning over an extended period of time.