New boundaries and dissociation of the mouse hippocampus along the dorsal‐ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities

Abstract

In rodents, gene-expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, the intermediate and the ventral hippocampal formation (HF) are distinct entities. These findings are underpinned by behavioral studies showing a dissociable role of dorsal and ventral HF in learning, memory, stress and emotional processing. However, up to now, the molecular basis of such differences in relation to discrete boundaries is largely unknown. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA, kainate and mGluR 2/3 , GABAergic GABA A (including benzodiazepine binding sites), GABA B , dopaminergic D 1/5 and noradrenergic α 1 and α 2 receptors as key modulators for signal transmission in hippocampal functions, using quantitative in vitro receptor autoradiography along the dorsal-ventral axis of the mouse HF. Beside general different receptor profiles of the dentate gyrus (DG) and Cornu Ammonis fields (CA1, CA2, CA3, CA4/hilus), we detected substantial differences between dorsal, intermediate and ventral subdivisions and individual layers for all investigated receptor types, except GABA B. For example, striking higher densities of α 2 receptors were detected in the ventral DG, while the dorsal DG possesses higher numbers of kainate, NMDA, GABA A and D 1/5 receptors. CA1 dorsal and intermediate subdivisions showed higher AMPA, NMDA, mGluR 2/3 , GABA A , D 1/5 receptors, while kainate receptors are higher expressed in ventral CA1, and noradrenergic α 1 and α 2 receptors in the intermediate region of CA1. CA2 dorsal was distinguished by higher kainate, α 1 and α 2 receptors in the intermediate region, while CA3 showed a more complex dissociation. Our findings resulted not only in a clear segmentation of the mouse hippocampus along the dorsal-ventral axis, but also provides insights into the neurochemical basis and likely associated physiological processes in hippocampal functions. Therein, the presented data has a high impact for future studies modeling and investigating dorsal, intermediate and ventral hippocampal dysfunction in relation to neurodegenerative diseases or psychiatric disorders.

Suppression of adult cytogenesis in the rat brain leads to sex‐differentiated disruption of the HPA axis activity

“…Complementarily, increasing evidence shows spatial segmentation of function, neurotransmitter density and synaptic input occurs in a gradient along the longitudinal axis 64,65 . In several species and rodent strains, including in Sprague Dawley rats (the one used in this study), hABN have been reported to be in higher number in the dorsal than in the ventral hippocampus 66–71 .…”

The Oscillatory Profile Induced by the Anxiogenic Drug FG-7142 in the Amygdala–Hippocampal Network Is Reversed by Infralimbic Deep Brain Stimulation: Relevance for Mood Disorders

“…The hippocampus is anatomically, neurochemically, and functionally subdivided along the septotemporal axis into dorsal, intermediate, and ventral regions [51][52][53][54]. While the dorsal hippocampus (dHPC) is mainly related to cortical regions and involved in cognitive processing, the ventral hippocampus (vHPC) has reciprocal projections to the amygdala and hypothalamus, and processes emotional and stress-related behaviors.…”

“…However, Strange and colleagues suggested a gradient of functional hippocampal domains instead of precise distributed functions [37]. In addition, the neurochemical organization of the hippocampal formation evidences a high density of adrenergic receptors in the ventral region [54], which is relevant in stress response and depression and their links with decreased neurogenesis.…”

Arbitration of Approach-Avoidance Conflict by Ventral Hippocampus

“…It is now known that the HPC can be anatomically and functionally separated into dorsal and ventral subregions (posterior and anterior, respectively, in humans and non-human primates) (Fanselow and Dong, 2010;Bach et al, 2014) and the function of these discrete subregions is generally conserved across species (Ito and Lee, 2016). It is further postulated based on molecular and morphological signatures across the dorsalventral axis that a third intermediate subregion of the HPC should be considered when defining HPC subregions (Fanselow and Dong, 2010;Lothmann et al, 2020).…”