Dentate granule cells, at the gate of the hippocampus, use coincidence detection of synaptic inputs to code afferent information under a sparse firing regime. In both human patients and animal models of temporal lobe epilepsy, mossy fibers sprout to form an aberrant glutamatergic network between dentate granule cells. These new synapses operate via long-lasting kainate receptor-mediated events, which are not present in the naive condition. Here, we report that in chronic epileptic rat, aberrant kainate receptors in interplay with the persistent sodium current dramatically expand the temporal window for synaptic integration. This introduces a multiplicative gain change in the input-output operation of dentate granule cells. As a result, their sparse firing is switched to an abnormal sustained and rhythmic mode. We conclude that synaptic kainate receptors dramatically alter the fundamental coding properties of dentate granule cells in temporal lobe epilepsy.
The ability to flexibly navigate an environment relies on a hippocampal-dependent cognitive map. External space can be internally mapped at different spatial resolutions. However, whether hippocampal spatial coding resolution can rapidly adapt to local features of an environment remains unclear. To explore this possibility, we recorded the firing of hippocampal neurons in mice navigating virtual reality environments, embedding or not local visual cues (virtual 3D objects) in specific locations. Virtual objects enhanced spatial coding resolution in their vicinity with a higher proportion of place cells, smaller place fields, increased spatial selectivity and stability. This effect was highly dynamic upon objects manipulations. Objects also improved temporal coding resolution through improved theta phase precession and theta timescale spike coordination. We propose that the fast adaptation of hippocampal spatial coding resolution to local features of an environment could be relevant for large-scale navigation.
1Animals can flexibly navigate in their environment. This ability is thought to rely on an 2 internal cognitive map. An open question concerns the influence of local sensory cues on the 3 cognitive map and notably their putative contribution to setting its spatial resolution. Here 4 we compared the firing of hippocampal principal cells in mice navigating virtual reality 5 environments in the presence or absence of local visual cues (virtual 3D objects). Objects 6 improved the spatial representation both quantitatively (higher proportion of place cells) 7 and qualitatively (smaller place fields with increased spatial selectivity and stability). This 8 gain in spatial coding resolution was more pronounced near the objects and could be rapidly 9 tuned by their manipulations. In addition, place cells displayed improved theta phase 10 precession in the presence of objects. Thus the hippocampal mapping system can 11 dynamically adjust its spatial coding resolution to local sensory cues available in the 12 environment. 13All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
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