Hippocampal interlamellar cell-cell connectome that counts.

The hippocampus is regarded as a cognition hub, particularly for learning and memory. Previously, neuronal mechanisms underlying various cognitive functions are delineated with the lamellar hippocampal circuitry, dentate gyrus-CA3 or CA2-CA1, within the transverse plane. More recently, interlamellar (often referred to as longitudinal) projections have received intensive attention to help understand signal convergence and divergence in cognition and behavior. Signal propagation along the longitudinal axis is evidenced by axonal arborization patterns and synaptic responses to electro- and photo-stimulation, further demonstrating that information flow is more enriched in the longitudinal plane than the transverse plane. Here, we review the significance of longitudinal connections for cognition, discuss a putative circuit mechanism of place coding, and suggest the reconceptualization of the hippocampal circuitry.

Dynamics of longitudinal dentate gyrus axons associated with seizure.

KEY POINTS: Axon collaterals of DG granule neurons project towards neighbouring DG granule cell layer Longitudinal axons in the DG-DG circuit possess denser synapses than transverse axons in the DG-CA3 circuit The size of varicosities of the longitudinal axons, but not transverse ones, is regulated by seizures as measured behaviourally Varicosity size of DG-DG axons can be a symptomatic marker of DG-related brain diseases ABSTRACT: The hippocampus network has captured the attention of neuroscientists as a model for understanding cognition and behaviour. Previously, we have identified interlamellar, namely longitudinal, axons between CA1 pyramidal neurons analogous to recurrent connections between CA3 pyramidal neurons. Currently it is unknown whether longitudinal axons of DG granule neurons are present and how they are associated with the behavioural symptoms of seizure. We found longitudinal axons projections from DG granule cells extending to neighbouring DG granule cell layers. These DG-DG axons have more numerous varicosities and are thinner than the DG-CA3 axons, suggesting heavy synaptic formation along a longitudinal axis. Furthermore, the size of varicosities in the DG-DG but not DG-CA3 axons is regulated by seizures as measured behaviourally. The results suggest that the dynamics of longitudinal DG axons is a symptomatic marker of DG-related brain diseases.

Altered synaptic plasticity of the longitudinal dentate gyrus network in noise-induced anxiety.

Anxiety is characteristic comorbidity of noise-induced hearing loss (NIHL), which causes physiological changes within the dentate gyrus (DG), a subfield of the hippocampus that modulates anxiety. However, which DG circuit underlies hearing loss-induced anxiety remains unknown. We utilize an NIHL mouse model to investigate short- and long-term synaptic plasticity in DG networks. The recently discovered longitudinal DG-DG network is a collateral of DG neurons synaptically connected with neighboring DG neurons and displays robust synaptic efficacy and plasticity. Furthermore, animals with NIHL demonstrate increased anxiety-like behaviors similar to a response to chronic restraint stress. These behaviors are concurrent with enhanced synaptic responsiveness and suppressed short- and long-term synaptic plasticity in the longitudinal DG-DG network but not in the transverse DG-CA3 connection. These findings suggest that DG-related anxiety is typified by synaptic alteration in the longitudinal DG-DG network.