Biology subjects

Shobe, J. L.

Publications and source records attributed to Shobe, J. L..

3 recordsLinked to original sources

bioRxiv2025

Dentate spikes comprise a continuum of relative input strength from the lateral and medial entorhinal cortex.

Hippocampal dentate spikes (DS) are synchronous population events generated in the dentate gyrus thought to support memory processing. DS are classified into type 1 (DS1) and type 2 (DS2) based on current sinks in the outer or middle molecular layer, where the axons of the lateral or medial entorhinal cortex terminate, respectively. This widely used classification method constrains DS into a bimodal distribution without properly testing whether such constraint is appropriate. Here we utilized silicon probe recordings with high spatial resolution spanning all layers of the dentate gyrus and discovered that the contribution of LEC/MEC inputs to DS follows a continuous distribution. We introduce a third type (DS3) that captures a previously unreported component of the distribution: simultaneous current sinks in the outer/middle molecular layer, suggestive of synchronized activation from the LEC/MEC which could facilitate binding. We verify DS3 in several data sets from independent laboratories and characterize their brain state dependence and neural recruitment.

neuroscience↗

bioRxiv2025

Enriched experience increases reciprocal synaptic connectivity and coding sparsity in higher-order cortex

The integration of new information during sleep reshapes cortical representations that support categorical knowledge. Auto-associative attractor network theories predict that reciprocal excitatory connections help form stable categorical attractors, but direct evidence is missing. We tested this using ten weeks of enriched experience (ENR) in mice as a model for knowledge accumulation and recorded single-unit activity across hippocampus and neocortex. ENR induced significant remodeling in high- but not low-level neocortex, with a shift from unidirectional to bidirectional excitatory-excitatory connections, suggestive of increased cell assemblies. This was accompanied by increased inhibitory-to-excitatory connections and sparser, more orthogonal population activity during awake rest and slow-wave sleep, particularly in deep layers. Thus, ENR reorganizes cortical circuits into a symmetric, inhibition-balanced network that improves coding efficiency, supporting long-standing attractor network predictions.

neuroscience↗

bioRxiv2025

Cognitive enrichment improves spatial memory and alters hippocampal synaptic connectivity in a mouse model for early-life stress

Early life stress (ELS) and enrichment often have opposing effects on long-term cognitive abilities. Deprivation, such as institutionalized care during early childhood neurodevelopmental periods, results in lifelong working memory and recall deficits. In contrast, enrichment facilitates new learning and slows cognitive decline due to aging and neurodegenerative diseases. Similarly, in rodent models, enrichment facilitates learning whereas ELS induces prominent spatial memory deficits. Environmental enrichment (EE) and ELS can cause opposing changes in hippocampal structure (e.g. shifts in synaptic density) that largely depend on experimental conditions. However, it remains untested whether EE can rescue the behavioral disruptions caused by ELS and how this would impact the hippocampus at advanced ages. To address this, we conducted a longitudinal study on ELS mice, extensively training them on a cognitive enrichment track (ET) or an exercise alone control track (CT). After this, the mice underwent repeated memory testing followed by brain extraction for anatomical analysis of their hippocampus. We found that ET reversed spatial memory deficits at 6, 13 and 20 months and reduced the number of dentate gyrus (DG) to CA3 synapses. Surprisingly, this reduction occurred at excitatory MF synapses surrounding CA3 somas in the stratum pyramidale--a layer not typically associated with MF terminals. Collectively, these findings suggest that cognitive enrichment during early adulthood may reverse ELS-induced spatial memory deficits by adjusting synaptic connectivity between the DG and CA3.

animal behavior and cognition↗