Fenton, A. | bioRxiv Science

bioRxiv2017

On how the dentate gyrus contributes to memory discrimination

SummaryThe dentate gyrus (DG) is crucial for behaviorally discriminating similar spatial memories, predicting that dentate gyrus place cells change (\"remap\") spatial tuning (\"place fields\") for memory discrimination. This prediction was never tested, although DG place cells remap across similar environments without memory tasks. We confirm this prior finding, then demonstrate that DG place fields do not remap across spatial tasks that require DG-dependent memory discrimination. Instead of remapping, place-discriminating discharge is observed transiently amongst DG place cells, particularly where memory discrimination is most necessary. The DG network signals memory discrimination by expressing distinctive sub-second network patterns of co-firing amongst principal cells at memory discrimination sites. This is accompanied by increased coupling of discharge from excitatory principal cells and inhibitory interneurons. Instead of remapping, these findings identify that memory discrimination is signaled by sub-second patterns of correlated discharge within the dentate network.\n\neTOC blurbvan Dijk and Fenton report that dentate gyrus place cells signal memory discrimination not by remapping, but by variable sub-second patterns of coordinated place cell network discharge and enhanced discharge coupling between excitatory and inhibitory neurons, at sites of memory discrimination.\n\nHighlightsO_LIDentate gyrus-dependent memory discrimination does not require place cell remapping\nC_LIO_LIDentate neural correlates of pattern discrimination are transient, lasting seconds\nC_LIO_LISub-second dentate network discharge correlations signal memory discrimination\nC_LIO_LIDentate excitatory-inhibitory coupling is increased at memory discrimination sites\nC_LI

neuroscience↗

bioRxiv2017

Analysis of hippocampal transcriptomic responses to technical and biological perturbations

Cost-effective next-generation sequencing has made unbiased gene expression analysis possible. Single-neuron gene expression studies may be especially important for understanding nervous system structure and function because of the neuron-specific functionality and plasticity that defines functional neural circuits. Cellular dissociation is a prerequisite technical manipulation for single-cell and single cell-population studies, but the extent to which the cellular dissociation process cells affects neural gene expression has not been determined, nor has it been determined how gene expression is altered by the stress that accompanies many of the behavioral manipulations that are required to study learning and memory and other cognitive functions. Here, we determined to which extent cellular dissociation-induced changes in hippocampal gene expression might confound studies on the behavioral and physiological functions of the hippocampus. We processed tissue punch samples from the dentate gyrus (DG), CA3, and CA1 hippocampus subfields using either a tissue homogenization protocol or a cellular dissociation protocol in preparation for RNA sequencing analysis to evaluate the impact of the tissue preparation. Then, we evaluated the effect of stressful experience and cognitive training on hippocampus subfield specific gene expression and determined to which extent these response overlap with the cellular dissociation response. Finally, we assessed the extent to which the subfield-specific gene expression patterns are consistent with those identified in a recently published hippocampus subfield-specific gene expression database. We report substantial differences in baseline subfield-specific gene expression, that 1% of the hippocampal transcriptome is altered by the process of cellular dissociation, that an even weaker alteration is detected 24 h after stressful experience, and that while these alterations are largely distinct from the subfield specific response of the hippocampus transcriptome to cognitive training, there is nonetheless some important confounding overlap. These findings of the concordant and discordant effects of technical and behavioral manipulations should inform the design of future neural transcriptome studies and thus facilitate a more comprehensive understanding of hippocampal function.

neuroscience↗