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 α₁ and α₂ 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 α₂ 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 α₁ and α₂ receptors in the intermediate region of CA1. CA2 dorsal was distinguished by higher kainate, α₁ and α₂ 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.

Keywords: atlas; dorsal-ventral axis; hippocampus; neurotransmitter receptors; receptor autoradiography; rodent.