Lesions Of Dorsal Striatum Research Articles

Apical intercalated cell cluster: A distinct sensory regulator in the amygdala.

GABAergic neurons regulate different aspects of information processing in the amygdala. Among these are clusters of intercalated cells (ITCs), which have been implicated in fear-related behaviors. Although a few of the ITC clusters have been studied, the functional role of apical ITCs (apITCs) is unknown. Here, we combine monosynaptic rabies tracing with optogenetics and demonstrate that apITCs receive synaptic input from medial geniculate nucleus (MGm), posterior intralaminar nucleus (PIN), and medial dorsal nucleus of the thalamus and from a diverse range of cortical areas including temporal association, entorhinal, insular, piriform, and somatosensory cortex. Upon fear learning, PIN/MGm inputs are strengthened, indicative of their involvement in fear behaviors. 3-D reconstruction of apITCs reveals local arborization and innervation of the dorsal striatum and lateral amygdala. We further show that apITCs provide sensory feedforward inhibition to LA principal cells, a putative mechanism for controlling plasticity during fear learning.

Role of the medial prefrontal cortex and nucleus accumbens in an operant model of checking behaviour and uncertainty.

Background:Excessive checking is a common, debilitating symptom of obsessive–compulsive disorder. To further examine cognitive processes underpinning checking behaviour, and clarify how and why checking develops, we designed a novel operant paradigm for rats, the observing response task. The present study used the observing response task to investigate checking behaviour following excitotoxic lesions of the medial prefrontal cortex, nucleus accumbens core and dorsal striatum, brain regions considered to be of relevance to obsessive–compulsive disorder.Methods:In the observing response task, rats pressed an ‘observing’ lever for information (provided by light onset) about the location of an ‘active’ lever that provided food reinforcement. Following training, rats received excitotoxic lesions of the regions described above and performance was evaluated post-operatively before histological processing.Results:Medial prefrontal cortex lesions selectively increased functional checking with a less-prominent effect on non-functional checking and reduced discrimination accuracy during light information periods. Rats with nucleus accumbens core lesions made significantly more checking responses than sham-lesioned rats, including both functional and non-functional checking. Dorsal striatum lesions had no direct effect on checking per se, but reduced both active and inactive lever presses, and therefore changed the relative balance between checking responses and instrumental responses.Conclusions:These results suggest that the medial prefrontal cortex and nucleus accumbens core are important in the control of checking, perhaps via their role in processing uncertainty of reinforcement, and that dysfunction of these regions may therefore promote excessive checking behaviour, possibly relevant to obsessive-compulsive disorder.

Touchscreen tasks in mice to demonstrate differences between hippocampal and striatal functions

In mammals, hippocampal and striatal regions are engaged in separable cognitive processes usually assessed through species-specific paradigms. To reconcile cognitive testing among species, translational advantages of the touchscreen-based automated method have been recently promoted. However, it remains undetermined whether similar neural substrates would be involved in such behavioral tasks both in humans and rodents. To address this question, the effects of hippocampal or dorso-striatal fiber-sparing lesions were first assessed in mice through a battery of tasks (experiment A) comprising the acquisition of two touchscreen paradigms, the Paired Associates Learning (dPAL) and Visuo-Motor Conditional Learning (VMCL) tasks, and a more classical T-maze alternation task. Additionally, we sought to determine whether post-acquisition hippocampal lesions would alter memory retrieval in the dPAL task (experiment B). Pre-training lesions of dorsal striatum caused major impairments in all paradigms. In contrast, pre-training hippocampal lesions disrupted the performance of animals trained in the T-maze assay, but spared the acquisition in touchscreen tasks. Nonetheless, post-training hippocampal lesions severely impacted the recall of the previously learned dPAL task. Altogether, our data show that, after having demonstrated their potential in genetically modified mice, touchscreens also reveal perfectly adapted to taxing functional implications of brain structures in mice by means of lesion approaches. Unlike its human counterpart requiring an intact hippocampus, the acquisition of the dPAL task requires the integrity of the dorsal striatum in mice. The hippocampus only later intervenes, when acquired information needs to be retrieved. Touchscreen assays may therefore be suited to study striatal- or hippocampal-dependent forms of learnings in mice.

Lesions of dorsal striatum eliminate lose‐switch responding but not mixed‐response strategies in rats

We used focal brain lesions in rats to examine how dorsomedial (DMS) and dorsolateral (DLS) regions of the striatum differently contribute to response adaptation driven by the delivery or omission of rewards. Rats performed a binary choice task under two modes: one in which responses were rewarded on half of the trials regardless of choice; and another 'competitive' one in which only unpredictable choices were rewarded. In both modes, control animals were more likely to use a predictable lose-switch strategy than animals with lesions of either DMS or DLS. Animals with lesions of DMS presumably relied more on DLS for behavioural control, and generated repetitive responses in the first mode. These animals then shifted to a random response strategy in the competitive mode, thereby performing better than controls or animals with DLS lesions. Analysis using computational models of reinforcement learning indicated that animals with striatal lesions, particularly of the DLS, had blunted reward sensitivity and less stochasticity in the choice mechanism. These results provide further evidence that the rodent DLS is involved in rapid response adaptation that is more sophisticated than that embodied by the classic notion of habit formation driven by gradual stimulus-response learning.

Metabotropic Glutamate Receptors 5 Blockade Reverses Spatial Memory Deficits in a Mouse Model of Parkinson's Disease

Visuo-spatial deficits are the most consistently reported cognitive abnormalities in Parkinson's disease (PD), and they are frequently associated to motor symptoms in the early stages of the disease when dopamine loss is moderate and still restricted to the caudate-putamen. The metabotropic glutamate receptor 5 (mGluR5) antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), has beneficial effects on motor symptoms in animal models of PD. However, the effects of MPEP on the cognitive deficits of the disease have never been investigated. Thus, the purpose of this study was to explore its therapeutic potentials by investigating its effects on the visuo-spatial deficits induced by 6-hydroxydopamine (6-OHDA) lesions of dorsal striatum in CD1 mice. The results demonstrated that systemic injections of MPEP (6, 12, and 24 mg/kg, i.p.) impair visuo-spatial discrimination in intact mice at high concentrations, whereas lower doses (1.5 and 3 mg/kg, i.p.) were void of effects. Nevertheless, when an ineffective dose (MPEP 3 mg/kg) was injected, either acutely or subchronically (8 days), it antagonized the visuo-spatial discrimination deficit induced by bilateral dopamine lesion of the striatum. Furthermore, the same treatment increased contralateral turning induced by L-DOPA in mice bearing unilateral 6-OHDA lesion. These results confirm the therapeutic potential of mGluR5 blockade on motor symptoms induced by reduced striatal dopamine function. Further, they demonstrate that mGluR5 blockade may also have beneficial effects on cognitive deficits induced by dopamine depletion.

The indirect amygdala–dorsal striatum pathway mediates conditioned freezing: Insights on emotional memory networks

The dorsal striatum (DS) is involved in various forms of learning and memory such as procedural learning, habit learning, reward-association and emotional learning. We have previously reported that bilateral DS lesions disrupt tone fear conditioning (TFC), but not contextual fear conditioning (CFC) [Ferreira TL, Moreira KM, Ikeda DC, Bueno OFA, Oliveira MGM (2003) Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning. Brain Res 987:17–24]. To further elucidate the participation of DS in emotional learning, in the present study, we investigated the effects of bilateral pretest (postraining) electrolytic DS lesions on TFC. Given the well-acknowledged role of the amygdala in emotional learning, we also examined a possible cooperation between DS and the amygdala in TFC, by using asymmetrical electrolytic lesions, consisting of a unilateral lesion of the central amygdaloid nucleus (CeA) combined to a contralateral DS lesion. The results show that pre-test bilateral DS lesions disrupt TFC responses, suggesting that DS plays a role in the expression of TFC. More importantly, rats with asymmetrical pre-training lesions were impaired in TFC, but not in CFC tasks. This result was confirmed with muscimol asymmetrical microinjections in DS and CeA, which reversibly inactivate these structures. On the other hand, similar pretest lesions as well as unilateral electrolytic lesions of CeA and DS in the same hemisphere did not affect TFC. Possible anatomical substrates underlying the observed effects are proposed. Overall, the present results underscore that other routes, aside from the well-established CeA projections to the periaqueductal gray, may contribute to the acquisition/consolidation of the freezing response associated to a TFC task. It is suggested that CeA may presumably influence DS processing via a synaptic relay on dopaminergic neurons of the substantia nigra compacta and retrorubral nucleus. The present observations are also in line with other studies showing that TFC and CFC responses are mediated by different anatomical networks.

Rats depend on habit memory for discrimination learning and retention

We explored the circumstances in which rats engage either declarative memory (and the hippocampus) or habit memory (and the dorsal striatum). Rats with damage to the hippocampus or dorsal striatum were given three different two-choice discrimination tasks (odor, object, and pattern). These tasks differed in the number of trials required for learning (approximately 10, 60, and 220 trials). Dorsal striatum lesions impaired discrimination performance to a greater extent than hippocampal lesions. Strikingly, performance on the task learned most rapidly (the odor discrimination) was severely impaired by dorsal striatum lesions and entirely spared by hippocampal lesions. These findings suggest that discrimination learning in the rat is primarily supported by the dorsal striatum (and habit memory) and that rats engage a habit-based memory system even for a task that takes only a few trials to acquire. Considered together with related studies of humans and nonhuman primates, the findings suggest that different species will approach the same task in different ways.

Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning

It has been suggested that the striatum mediates hippocampus-independent memory tasks. Classical fear conditioning to a discrete stimulus such as a tone is not affected by hippocampal lesion, whereas contextual fear conditioning is an hippocampus dependent task. The purpose of the present study was to verify the effect of dorsal striatal lesions on tone and contextual fear conditioning. The lesioned rats were not impaired in contextual fear conditioning but in tone fear conditioning both electrolytically and neurotoxically lesioned animals showed less freezing compared with controls. The lesion effect was observed after a postoperative recovery period of 14 days but not after 2 months. The results support the hypothesis that the dorsal striatum is involved in hippocampus-independent memory tasks, but, in spite of this involvement, it does not seem to be a critical structure.

Effects of dorsal-striatum lesions and fimbria-fornix lesions on the problem-solving strategies of rats in a shallow water maze.

In solving a spatial problem, animals can use a place, cue, or response strategy. The present research was designed to evaluate the role of dorsal striatum (DS) in spatial problem solving and to compare it with that of fimbria fornix (FF). Rats were trained with a place + cue task in a shallow pool, then were divided into three groups (DS, FF, control), and lesions were made in the corresponding areas. After retraining, four probe tests were given: Test 1 (start position moved), Test 2 (goal and start positions moved), Test 3 (invisible goal), and Test 4 (curtain test). The test results suggest that the DS and Control groups performed the original task by using the place strategy, whereas the FF group used the cue strategy, which strongly implies that the DS group was impaired in the use of the cue strategy. This research also provides evidence supporting the usefulness of a shallow pool in evaluating animal behavior.

Contrasting effects of central nucleus of the amygdala and dorsal striatum lesions on active avoidance learning and its contextual modification

We examined the effects of a contextual modification after acquisition of a two-way signalled active avoidance task in central nucleus of the amygdala (CNA) and dorsal striatum (DS) lesioned rats. Results showed that CNA lesioned rats learned to avoid shocks when the tone was presented, as rapidly as sham-operated animals showing that they were able to learn normally the different associations between the stimuli. In contrast, DS lesioned rats were retarded in learning the avoidance response. A contextual modification leaded to a transient disruption of performances in sham-operated rats and to a long-lasting impairment in CNA rats, while DS rats were unaffected. This post-acquisition contextual change provided further information about the way CNA and DS rats had learned the task. © 1997 John Wiley & Sons, Ltd.

Contrasting effects of central nucleus of the amygdala and dorsal striatum lesions on active avoidance learning and its contextual modification

Contrasting effects of central nucleus of the amygdala and dorsal striatum lesions on active avoidance learning and its contextual modification