Neurocentre Magendie

Stephane VALERIO


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9 publication(s) depuis Avril 2008:

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Head direction (HD) cells fire when an animal faces a particular direction in its environment, and they are thought to represent the neural correlate of the animal's perceived spatial orientation. Previous studies have shown that vestibular information is critical for generating the HD signal but have not delineated whether information from all three semicircular canals or just the horizontal canals, which are primarily sensitive to angular head rotation in the horizontal (yaw) plane, are critical for the signal. Here, we monitored cell activity in the anterodorsal thalamus (ADN), an area known to contain HD cells, in epstatic circler (Ecl) mice, which have a bilateral malformation of the horizontal (lateral) semicircular canals. Ecl mice and their littermates that did not express the mutation (controls) were implanted with recording electrodes in the ADN. Results confirm the important role the horizontal canals play in forming the HD signal. Although normal HD cell activity (Raleigh's r > 0.4) was recorded in control mice, no such activity was found in Ecl mice, although some cells had activity that was mildly modulated by HD (0.4 > r > 0.2). Importantly, we also observed activity in Ecl mice that was best characterized as bursty-a pattern of activity similar to an HD signal but without any preferred firing direction. These results suggest that the neural structure for the HD network remains intact in Ecl mice, but the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable HD signal. SIGNIFICANCE STATEMENT: Cells in the anterior dorsal thalamic nucleus normally fire in relation to the animal's directional heading with respect to the environment-so-called head direction cells. To understand how these head direction cells generate their activity, we recorded single-unit activity from the anterior dorsal thalamus in transgenic mice that lack functional horizontal semicircular canals. We show that the neural network for the head direction signal remains intact in these mice, but that the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable head direction signal.

07/10/2014 | Genes Brain Behav   IF 3.3
Prefrontal neuronal circuits of contextual fear conditioning.
Rozeske RR, Valerio S, Chaudun F, Herry C

Over the past years, numerous studies have provided a clear understanding of the neuronal circuits and mechanisms involved in the formation, expression and extinction phases of conditioned cued fear memories. Yet, despite a strong clinical interest, a detailed understanding of these memory phases for contextual fear memories is still missing. Besides the well-known role of the hippocampus in encoding contextual fear behavior, growing evidence indicates that specific regions of the medial prefrontal cortex differentially regulate contextual fear acquisition and storage in both animals and humans that ultimately leads to expression of contextual fear memories. In this review, we provide a detailed description of the recent literature on the role of distinct prefrontal subregions in contextual fear behavior and provide a working model of the neuronal circuits involved in the acquisition, expression and generalization of contextual fear memories.

07/2013 | j cogn neurosci
Is navigation in virtual reality with FMRI really navigation?
Taube JS, Valerio S, Yoder RM

Identifying the neural mechanisms underlying spatial orientation and navigation has long posed a challenge for researchers. Multiple approaches incorporating a variety of techniques and animal models have been used to address this issue. More recently, virtual navigation has become a popular tool for understanding navigational processes. Although combining this technique with functional imaging can provide important information on many aspects of spatial navigation, it is important to recognize some of the limitations these techniques have for gaining a complete understanding of the neural mechanisms of navigation. Foremost among these is that, when participants perform a virtual navigation task in a scanner, they are lying motionless in a supine position while viewing a video monitor. Here, we provide evidence that spatial orientation and navigation rely to a large extent on locomotion and its accompanying activation of motor, vestibular, and proprioceptive systems. Researchers should therefore consider the impact on the absence of these motion-based systems when interpreting virtual navigation/functional imaging experiments to achieve a more accurate understanding of the mechanisms underlying navigation.

Head-direction cells have frequently been regarded as an internal 'compass' that can be used for navigation, although there is little evidence showing a link between their activity and spatial behavior. In a navigational task requiring the use of internal cues to return to a home location without vision (path integration), we found a robust correlation between head-direction cell activity and the rat's heading error in the rat's homing behavior. We observed two different correction processes that rats used to improve performance after an error. The more frequent one consists of 'resetting' the cell whenever the rat returns to the home location. However, we found that when large errors occur, the head-direction system has the ability to 'remap' and set a new reference frame, which is then used in subsequent trials. We also offer some insight into how these two correction processes operate when rats make an error.

06/2011 | J Neurophysiol   IF 2.7
Both visual and idiothetic cues contribute to head direction cell stability during navigation along complex routes.
Yoder RM, Clark BJ, Brown JE, Lamia MV, Valerio S, Shinder ME, Taube JS

Successful navigation requires a constantly updated neural representation of directional heading, which is conveyed by head direction (HD) cells. The HD signal is predominantly controlled by visual landmarks, but when familiar landmarks are unavailable, self-motion cues are able to control the HD signal via path integration. Previous studies of the relationship between HD cell activity and path integration have been limited to two or more arenas located in the same room, a drawback for interpretation because the same visual cues may have been perceptible across arenas. To address this issue, we tested the relationship between HD cell activity and path integration by recording HD cells while rats navigated within a 14-unit T-maze and in a multiroom maze that consisted of unique arenas that were located in different rooms but connected by a passageway. In the 14-unit T-maze, the HD signal remained relatively stable between the start and goal boxes, with the preferred firing directions usually shifting <45 degrees during maze traversal. In the multiroom maze in light, the preferred firing directions also remained relatively constant between rooms, but with greater variability than in the 14-unit maze. In darkness, HD cell preferred firing directions showed marginally more variability between rooms than in the lighted condition. Overall, the results indicate that self-motion cues are capable of maintaining the HD cell signal in the absence of familiar visual cues, although there are limits to its accuracy. In addition, visual information, even when unfamiliar, can increase the precision of directional perception.

05/2010 | Neurobiol Learn Mem   IF 3.4
Directional learning, but no spatial mapping by rats performing a navigational task in an inverted orientation.
Valerio S, Clark BJ, Chan JH, Frost CP, Harris MJ, Taube JS

Previous studies have identified neurons throughout the rat limbic system that fire as a function of the animal's head direction (HD). This HD signal is particularly robust when rats locomote in the horizontal and vertical planes, but is severely attenuated when locomoting upside-down (Calton & Taube, 2005). Given the hypothesis that the HD signal represents an animal's sense of directional heading, we evaluated whether rats could accurately navigate in an inverted (upside-down) orientation. The task required the animals to find an escape hole while locomoting inverted on a circular platform suspended from the ceiling. In Experiment 1, Long-Evans rats were trained to navigate to the escape hole by locomoting from either one or four start points. Interestingly, no animals from the 4-start point group reached criterion, even after 29 days of training. Animals in the 1-start point group reached criterion after about six training sessions. In Experiment 2, probe tests revealed that animals navigating from either 1- or 2-start points utilized distal visual landmarks for accurate orientation. However, subsequent probe tests revealed that their performance was markedly attenuated when navigating to the escape hole from a novel start point. This absence of flexibility while navigating upside-down was confirmed in Experiment 3 where we show that the rats do not learn to reach a place, but instead learn separate trajectories to the target hole(s). Based on these results we argue that inverted navigation primarily involves a simple directional strategy based on visual landmarks.

07/2008 | J Psychopharmacol   IF 3.6
Comparative effects of the dopaminergic agonists piribedil and bromocriptine in
Marighetto A, Valerio S, Philippin JN, Bertaina-Anglade V, Drieu la Rochelle C, Jaffard R, Morain P

The potential memory-enhancing properties of two dopamine agonists currently used

05/2008 | Behav Pharmacol   IF 2
The AMPA modulator S 18986 improves declarative and working memory performances
Marighetto A, Valerio S, Jaffard R, Mormede C, Munoz C, Bernard K, Morain P

The aim of this study was to further characterize the memory-enhancing profile of

INTRODUCTION: The comparative effects of a newly described specific alpha7 nAChR partial agonist, S 24795, and a cholinesterase inhibitor, donepezil, currently used as a symptomatic Alzheimer's disease treatment were studied in two mouse models of aging-related memory deficits. MATERIALS AND METHODS: We employed radial arm-maze paradigms assessing short-term working memory (STWM, experiment A) and mnemonic flexibility, a cardinal property of long-term declarative (LTDM, experiment B). Both compounds were administered daily at 0.3 and 1 mg/kg subcutaneously (~3 weeks). RESULTS: In the STWM experiment, vehicle-treated aged mice displayed a severe and persistent deficit in the retention of successive arm visits in comparison to younger controls. S 24795 at 1 mg/kg (trends at 0.3 mg/kg) and donepezil at 0.3 mg/kg (but not 1 mg/kg) exerted beneficial effects on this deficit: The performance of aged mice treated with these drugs remarkably increased across the testing days and almost reached young adult performance level. In the critical test trials of memory flexibility (i.e., LTDM), in experiment B, S 24795 at 1 mg/kg (trends at 0.3 mg/kg) and donepezil at the dose of 1 mg/kg (but not 0.3 mg/kg) improved aged mice performance. CONCLUSION: This preclinical demonstration that S 24795 restored specific age-related memory deficits with as much efficacy as donepezil adds to recent literature in highlighting the potential interest of an alpha7 nAChR drug as a symptomatic AD therapeutic.