Temporal Sensitivity Changes with Extended Training in a Bisection Task in a Transgenic Rat Model

The present study investigated temporal perception in a Huntington disease transgenic rat model using a temporal bisection procedure. After initial discrimination training in which animals learned to press one lever after a 2-s tone duration, and the other lever after a 8-s tone duration for food reward, the bisection procedure was implemented in which intermediate durations with no available reinforcement were interspersed with trials with the anchor durations. Bisection tests were repeated in a longitudinal design from 4 to 8 months of age. The results showed that response latencies evolved from a monotonic step-function to an inverted U-shaped function with repeated testing, a precursor of non-responding on trials with intermediate durations. We inferred that temporal sensitivity and incentive motivation combined to control the transformation of the bisection task from a two-choice task at the outset of testing to a three-choice task with repeated testing. Changes in the structure of the task and/or continued training were accompanied by improvement in temporal sensitivity. In sum, the present data highlight the possible joint roles of temporal and non-temporal factors in the temporal bisection task, and suggested that non-temporal factors may compensate for deficits in temporal processing

Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

Huntington\u27s disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

Selective hippocampal lesions in rats disrupt acquisition and retention of a positive patterning discrimination.

International audienceTo determine the contribution of the hippocampus in the processing of a configural positive patterning discrimination (PPD) task, discrimination between reinforced presentations of a tone plus light compound stimulus and nonreinforced presentations of each of its components (TL+/T-,L-) was examined using a conditioned-suppression paradigm. In the first experiment, rats demonstrated a rapid acquisition of the PPD with an appropriate discriminative responding. Rats submitted to posttraining hippocampal lesions (using multiple injections of ibotenic acid) were no longer able to master correctly the previously solved discrimination, demonstrating significant differences in their response rates during the 2 never-reinforced elemental stimulus presentations. In Experiment II, lesioned rats were not able to correctly learn the PPD, demonstrating the same pattern of responding as in Experiment I. These rats were also severely disrupted in a radial maze elimination task. Experiment IIIa indicated that, in a simple conditioning task (T+, L+), normal rats acquired a rapid conditioned suppression for both stimuli, with the tone being slightly more susceptible to conditioning than the light stimulus. In Experiment IIIb, conditioning to the compound tone plus light stimulus led to a clear conditioning to the tone and almost no conditioning to the light, suggesting an overshadowing from the tone to the light. Similar results were obtained in rats with hippocampal lesions. These results strongly suggest that the disruption showed by rats with hippocampal lesions in the PPD task cannot be due to an alteration of the relative salience of the stimulus. The inability of rats with hippocampal lesions to solve correctly the PPD is due to difficulties in eliminating responding to some unimportant events of the situation, reflecting a deficit in selective attention processes rather than in an ability to process configural stimuli. In the discussion, the putative role of the hippocampus in selective attentional processes is more fully discussed

Cerebellar deep nuclei involvement in cognitive adaptation and automaticity.

International audienceTo determine the role of the interpositus nuclei of cerebellum in rule-based learning and optimization processes, we studied (1) successive transfers of an initially acquired response rule in a cross maze and (2) behavioral strategies in learning a simple response rule in a T maze in interpositus lesioned rats (neurotoxic or electrolytic lesions). Even though lesioned animals showed no impairment in learning the initial stimulus-response association, they had difficulties in transferring the acquired adapted response rule, and in optimizing their response strategy. These results add information on the role of interpositus nuclei in adaptation to environmental changes

Rôle du cervelet dans les apprentissages (approches clinique, épidémiologique et expérimentale)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Rule-based learning impairment in rats with lesions to the dorsal striatum.

International audienceThe present study examined the effects of lesions to the dorsal striatum (DS) in Sprague-Dawley rats, when tested on the acquisition and successive shifts in the position of a goal arm in an eight-arm radial maze. In the procedure we used, rats had to retrieve the location of one baited arm among the eight arms of the maze after it had just been presented as a sample during a forced trial. After attainment of a fixed learning criterion, rats were submitted to five successive shifts in the goal location. Results showed that DS rats were able to learn the position of the goal arm during the acquisition phase as efficiently as sham-operated rats. In contrast, when the position of the goal arm was shifted, although DS rats were able to learn its new position, they made significantly more errors and required more sessions to reach criterion than sham-operated rats. These results suggested that both groups did not solve the task using the same behavioral strategy. The analysis of responses made suggested that sham-operated rats solved the task using the pairing rule between the forced and the free run (matching-to-sample rule), while DS rats solved the task using only visuo-spatial processing. These data therefore suggest that the dorsal striatum plays an important role in rule-learning ability

Dopamine agonists increase perseverative instrumental responses but do not restore habit formation in a rat model of Parkinsonism.

International audienceDopamine (DA) deafferentation of the dorsolateral striatum has been shown to prevent habit development, leaving instrumental behavior under action-outcome control that is persistently sensitive to modification of the motivational value of the reward. The present experiment further explored the basis of this dysfunction by examining the ability of intrastriatal DA agonist injections (D1 SKF 38393 or D2/D3 Quinpirole) during overtraining of a signaled instrumental task to restore habit formation in rats subjected to bilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. The results confirmed the impaired shift in performance from action to habit in control lesioned rats. However, lesioned rats repeatedly injected with quinpirole D2/D3 agonist showed an increase in non-rewarded instrumental responses (intertrials periods) during overtraining, suggesting the development of perseverative behavior. Following the procedure of devaluation, quinpirole D2/D3 agonist treatment, and to a lesser extent SKF 38393 D1 agonist, caused the persistence of sensitivity to reward devaluation, indicating clear goal-directed behavior despite extended training. This absence of restoration of habit formation by DA agonist treatment is discussed in the light of DA agonist effects in Parkinson patients

Conditioned hippocampal cellular response to a behaviorally silent conditioned stimulus.

International audienceMultiunit activity (MUA) was chronically recorded in the hippocampal CA3 field of rats using a blocking paradigm with conditioned suppression of lever pressing for food as the measure of conditioning. In Experiment 1, a classical blocking paradigm demonstrated the good conditionability of 2 stimuli (a light and a tone) and their respective ability to block each other. In Experiment 2, MUA was recorded in CA3 cells in rats submitted to a similar paradigm. Four groups received either tone (groups B and B1) or click (groups BC and B1C) conditioned stimulus (CS) presentations that were followed immediately by an electrical footshock (unconditioned stimulus, US). The rats were then given either 40 (groups B and BC) or 1 (groups B1 and B1C) tone + light-footshock presentations. During test sessions, the animals showed MUA responses to the added CS (light), with no conditioned suppression of lever presses occurring during CS presentations. The results of Experiment 3 strongly suggest that hippocampal increase in cellular activity to the light appeared at the first compound trial presentation. Conditioning to the light obtained by increasing the US intensity after the single compound trial suggests that the hippocampal response reflects a redundant CS-US association (light-shock). Long-term retention tests given 45 days after the end of conditioning revealed that behavioral and hippocampal responses could still be detected but only in response to the stimulus that had elicited a behavioral response during learning