Representation of Objects in Space by Two Classes of Hippocampal Pyramidal Cells

Humans can recognize and navigate in a room when its contents have been rearranged. Rats also adapt rapidly to movements of objects in a familiar environment. We therefore set out to investigate the neural machinery that underlies this capacity by further investigating the place cell–based map of the surroundings found in the rat hippocampus. We recorded from single CA1 pyramidal cells as rats foraged for food in a cylindrical arena (the room) containing a tall barrier (the furniture). Our main finding is a new class of cells that signal proximity to the barrier. If the barrier is fixed in position, these cells appear to be ordinary place cells. When, however, the barrier is moved, their activity moves equally and thereby conveys information about the barrier's position relative to the arena. When the barrier is removed, such cells stop firing, further suggesting they represent the barrier. Finally, if the barrier is put into a different arena where place cell activity is changed beyond recognition (“remapping”), these cells continue to discharge at the barrier. We also saw, in addition to barrier cells and place cells, a small number of cells whose activity seemed to require the barrier to be in a specific place in the environment. We conclude that barrier cells represent the location of the barrier in an environment-specific, place cell framework. The combined place + barrier cell activity thus mimics the current arrangement of the environment in an unexpectedly realistic fashion

Temporal Coordination of Hippocampal Neurons Reflects Cognitive Outcome Post-febrile Status Epilepticus

AbstractThe coordination of dynamic neural activity within and between neural networks is believed to underlie normal cognitive processes. Conversely, cognitive deficits that occur following neurological insults may result from network discoordination. We hypothesized that cognitive outcome following febrile status epilepticus (FSE) depends on network efficacy within and between fields CA1 and CA3 to dynamically organize cell activity by theta phase. Control and FSE rats were trained to forage or perform an active avoidance spatial task. FSE rats were sorted by those that were able to reach task criterion (FSE-L) and those that could not (FSE-NL). FSE-NL CA1 place cells did not exhibit phase preference in either context and exhibited poor cross-theta interaction between CA1 and CA3. FSE-L and control CA1 place cells exhibited phase preference at peak theta that shifted during active avoidance to the same static phase preference observed in CA3. Temporal coordination of neuronal activity by theta phase may therefore explain variability in cognitive outcome following neurological insults in early development

Bad Timing for Epileptic Networks: Role of Temporal Dynamics in Seizures and Cognitive Deficits

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Stereotypical activation of hippocampal ensembles during seizures

International audienceIn addition to affecting a person’s behaviour and risk of accidents, seizures are believed to result in various neuro-physiological changes that disrupt nervous system integrity. Although anti-epileptic treatments exist, they are not always effective and in some epilepsy syndromes, such as temporal lobe epilepsy, a large proportion of patients are pharmacologically resistant. In order to develop seizure-preventing treatments, researchers have been trying to identify the neurologicalprocesses leading to seizures. In this issue of Brain ,Neumannandco-workers use extracellular electro-physiological recordings to determine the temporal evolution of neuronal activity preceding and during spontaneous temporal lobe seizures in rats (Neumann et al., 2017). They provide evidence that ictal discharges preferentially recruit specific cell ensembles firing in stereotypical sequences. In contrast to the classic view that seizures result from excessive runaway excitation, they show that the predominant cell types activated during ictal discharges are fast-spiking, putative inhibitory interneurons

Etude des relations entre l'activité des cellules de lieu hippocampiques et les propriétés des comportements spatiaux chez le rat

Les cellules de lieu hippocampiques sont des neurones pyramidaux caractérisés par le fait que leur activité est corrélée à la position de l'animal dans l'espace. Le travail accompli dans cette thèse a eu pour objectif de préciser le rôle fonctionnel de l'activité de ces cellules et, précisément, de déterminer s'il existe des relations entre leur activité et les comportements spatiaux. Nous avons montré que lorsque la représentation codée par les cellules de lieu est mal orientée par rapport à l'environnement et donc par rapport à la tâche que l'animal doit réaliser, on observe une diminution de la performance spatiale. De plus, cette diminution semble spécifique des comportements reposant sur une représentation allocentrée de l'environnement. Nous avons aussi mis en évidence l'existence d'une relation fonctionnelle entre la décharge des cellules et un comportement d'exploration d'un groupe d'objets. Un changement de la configuration des objets s'accompagne à la fois d'une réactivation de l'exploration, et d'une modification de l'activité des cellules. Enfin, dans une dernière expérience, aucune preuve de l'influence des trajets antérieurs et futurs sur l'activité des cellules de lieu n'a été trouvée. L'ensemble des ces résultats suggère que les cellules de lieu jouent un rôle spécifique dans la genèse des comportements spatiaux mais n'exclut pas toutefois l'idée que ces cellules puissent participer à d'autres processus.AIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF

Cognitive Deficits Associated with Na(v)1.1 Alterations: Involvement of Neuronal Firing Dynamics and Oscillations

Brain oscillations play a critical role in information processing and may, therefore, be essential to uncovering the mechanisms of cognitive impairment in neurological disease. In Dravet syndrome (DS), a mutation in SCN1A, coding for the voltage-gated sodium channel Na(v)1.1, is associated with severe cognitive impairment and seizures. While seizure frequency and severity do not correlate with the extent of impairment, the slowing of brain rhythms may be involved. Here we investigate the role of Na(v)1.1 on brain rhythms and cognition using RNA interference. We demonstrate that knockdown of Na(v)1.1 impairs fast-and burst-firing properties of neurons in the medial septum in vivo. The proportion of neurons that fired phase-locked to hippocampal theta oscillations was reduced, and medial septal regulation of theta rhythm was disrupted. During a working memory task, this deficit was characterized by a decrease in theta frequency and was negatively correlated with performance. These findings suggest a fundamental role for Na(v)1.1 in facilitating fast-firing properties in neurons, highlight the importance of precise temporal control of theta frequency for working memory, and imply that Na(v)1.1 deficits may disrupt information processing in DS via a dysregulation of brain rhythms

Autistic traits in epilepsy models: Why, when and how?

International audienceAutism spectrum disorder (ASD) is a common comorbidity of epilepsy and seizures and/or epileptiform activity are observed in a significant proportion of ASD patients. Current research also implies that autistic traits can be observed to a various degree in mice and rats with seizures. This suggests that there are shared mechanisms in both ASD and epilepsy syndromes. Here, we first review the standard, validated methods used to assess autistic traits in animal models as well as their limitations with regards to epilepsy models. We then discuss two of the potential pathological processes that could be shared between ASD and epilepsy. We first focus on functional implications of neuroinflammation including changes to excitable networks mediated by inflammatory regulators. Finally we examine mechanisms at the cellular and network level involved in neuronal excitability, timing and network coordination that may directly lead to behavioral disturbances present in both epilepsy and ASD. This mini-review summarizes the work first presented at an Investigators Workshop at the 2016 American Epilepsy Society meeting

Les bases neurales de la mémoire spatiale chez l’animal : que nous disent les neurones de Phippocampe ?

Les travaux récents d’enregistrement de l’activité neuronale unitaire chez le rat libre de se déplacer montrent l’existence de deux populations de neurones signalant l’emplacement ou l’orientation courante de l’animal : les cellules de lieu que l’on trouve en particulier dans l’hippocampe, et les cellules d’orientation de la tête que l’on trouve dans des aires anatomiquement et fonctionnellement reliées à l’hippocampe. Les propriétés de ces deux populations de neurones montrent leur forte dépendance vis-à-vis des informations provenant de l’environnement, et suggèrent leur participation dans les comportements reposant sur la mémoire spatiale. Conjointement, les cellules de lieu et les cellules d’orientation de la tête participeraient à un réseau neuronal permettant à l’animal de s’orienter dans l’espace, et de mémoriser des lieux. Ce réseau pourrait également être à l’œuvre dans l’espèce humaine, en particulier pour le codage des événements spécifiques en mémoire épisodique

Focal Dorsal Hippocampal Nav1.1 Knock Down Alters Place Cell Temporal Coordination and Spatial Behavior

International audienceAlterations in the voltage-gated sodium channel Nav.1.1 are implicated in various neurological disorders, including epilepsy, Alzheimer's disease, and autism spectrum disorders. Previous studies suggest that the reduction of Nav1.1 expression leads to a decrease of fast spiking activity in inhibitory neurons. Because interneurons (INs) play a critical role in the temporal organization of neuronal discharge, we hypothesize that Nav1.1 dysfunction will negatively impact neuronal coordination in vivo. Using shRNA interference, we induced a focal Nav1.1 knock-down (KD) in the dorsal region of the right hippocampus of adult rats. Focal, unilateral Nav1.1 KD decreases the performance in a spatial novelty recognition task and the firing rate in INs, but not in pyramidal cells. It reduced theta/gamma coupling of hippocampal oscillations and induced a shift in pyramidal cell theta phase preference. Nav1.1 KD degraded spatial accuracy and temporal coding properties of place cells, such as theta phase precession and compression of ongoing sequences. Aken together, these data demonstrate that a deficit in Nav1.1 alters the temporal coordination of neuronal firing in CA1 and impairs behaviors that rely on the integrity of this network. They highlight the potential contribution of local inhibition in neuronal coordination and its impact on behavior in pathological conditions