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

Functional Network Changes in Hippocampal CA1 after Status Epilepticus Predict Spatial Memory Deficits in Rats

Status epilepticus (SE) is a common neurological emergency, which has been associated with subsequent cognitive impairments. Neuronal death in hippocampal CA1 is thought to be an important mechanism of these impairments. However, it is also possible that functional interactions between surviving neurons are important. In this study we recorded in vivo single-unit activity in the CA1 hippocampal region of rats while they performed a spatial memory task. From these data we constructed functional networks describing pyramidal cell interactions. To build the networks, we used maximum entropy algorithms previously applied only to in vitro data. We show that several months following SE pyramidal neurons display excessive neuronal synchrony and less neuronal reactivation during rest compared with those in healthy controls. Both effects predict rat performance in a spatial memory task. These results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition

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

A Selective Interplay between Aberrant EPSPKA and INaP Reduces Spike Timing Precision in Dentate Granule Cells of Epileptic Rats

Spike timing precision is a fundamental aspect of neuronal information processing in the brain. Here we examined the temporal precision of input–output operation of dentate granule cells (DGCs) in an animal model of temporal lobe epilepsy (TLE). In TLE, mossy fibers sprout and establish recurrent synapses on DGCs that generate aberrant slow kainate receptor–mediated excitatory postsynaptic potentials (EPSPKA) not observed in controls. We report that, in contrast to time-locked spikes generated by EPSPAMPA in control DGCs, aberrant EPSPKA are associated with long-lasting plateaus and jittered spikes during single-spike mode firing. This is mediated by a selective voltage-dependent amplification of EPSPKA through persistent sodium current (INaP) activation. In control DGCs, a current injection of a waveform mimicking the slow shape of EPSPKA activates INaP and generates jittered spikes. Conversely in epileptic rats, blockade of EPSPKA or INaP restores the temporal precision of EPSP–spike coupling. Importantly, EPSPKA not only decrease spike timing precision at recurrent mossy fiber synapses but also at perforant path synapses during synaptic integration through INaP activation. We conclude that a selective interplay between aberrant EPSPKA and INaP severely alters the temporal precision of EPSP–spike coupling in DGCs of chronic epileptic rats

Dual coding with STDP in a spiking recurrent neural network model of the hippocampus.

The firing rate of single neurons in the mammalian hippocampus has been demonstrated to encode for a range of spatial and non-spatial stimuli. It has also been demonstrated that phase of firing, with respect to the theta oscillation that dominates the hippocampal EEG during stereotype learning behaviour, correlates with an animal's spatial location. These findings have led to the hypothesis that the hippocampus operates using a dual (rate and temporal) coding system. To investigate the phenomenon of dual coding in the hippocampus, we examine a spiking recurrent network model with theta coded neural dynamics and an STDP rule that mediates rate-coded Hebbian learning when pre- and post-synaptic firing is stochastic. We demonstrate that this plasticity rule can generate both symmetric and asymmetric connections between neurons that fire at concurrent or successive theta phase, respectively, and subsequently produce both pattern completion and sequence prediction from partial cues. This unifies previously disparate auto- and hetero-associative network models of hippocampal function and provides them with a firmer basis in modern neurobiology. Furthermore, the encoding and reactivation of activity in mutually exciting Hebbian cell assemblies demonstrated here is believed to represent a fundamental mechanism of cognitive processing in the brain

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

International audienc

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