Abstract

The uptake, transmission and processing of sensory olfactory information is modulated by inhibitory and excitatory receptors in the olfactory system. Previous studies have focused on the function of individual receptors in distinct brain areas, but the receptor architecture of the whole system remains unclear. Here, we analyzed the receptor profiles of the whole olfactory system of adult male mice. We examined the distribution patterns of glutamatergic (AMPA, kainate, mGlu2/3, and NMDA), GABAergic (GABAA, GABAA(BZ), and GABAB), dopaminergic (D1/5) and noradrenergic (α1 and α2) neurotransmitter receptors by quantitative in vitro receptor autoradiography combined with an analysis of the cyto- and myelo-architecture. We observed that each subarea of the olfactory system is characterized by individual densities of distinct neurotransmitter receptor types, leading to a region- and layer-specific receptor profile. Thereby, the investigated receptors in the respective areas and strata showed a heterogeneous expression. Generally, we detected high densities of mGlu2/3Rs, GABAA(BZ)Rs and GABABRs. Noradrenergic receptors revealed a highly heterogenic distribution, while the dopaminergic receptor D1/5 displayed low concentrations, except in the olfactory tubercle and the dorsal endopiriform nucleus. The similarities and dissimilarities of the area-specific multireceptor profiles were analyzed by a hierarchical cluster analysis. A three-cluster solution was found that divided the areas into the (1) olfactory relay stations (main and accessory olfactory bulb), (2) the olfactory cortex (anterior olfactory cortex, dorsal peduncular cortex, taenia tecta, piriform cortex, endopiriform nucleus, entorhinal cortex, orbitofrontal cortex) and the (3) olfactory tubercle, constituting its own cluster. The multimodal receptor-architectonic analysis of each component of the olfactory system provides new insights into its neurochemical organization and future possibilities for pharmaceutic targeting.

Highlights

  • Olfactory areas form a highly interconnected network to process chemical olfactory information for olfactory recognition, memory, mating, and learning in mice

  • Olfactory System Receptor Profiles cortex, the taenia tecta, the dorsal peduncular cortex, the olfactory tubercle, the piriform cortex with the dorsal endopiriform nucleus and the entorhinal cortex

  • Receptors for noradrenaline and dopamine were observed in the anterior olfactory cortex (Fallon and Moore, 1978), but we found significant differences in the subareas with respect to the receptor distribution

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Summary

Introduction

Olfactory areas form a highly interconnected network to process chemical olfactory information for olfactory recognition, memory, mating, and learning in mice. Olfactory System Receptor Profiles cortex (anterior olfactory nucleus), the taenia tecta (dorsal, ventral), the dorsal peduncular cortex, the olfactory tubercle, the piriform cortex with the dorsal endopiriform nucleus and the entorhinal cortex (lateral and medial). These structures directly receive input from the main olfactory bulb and project back (Luskin and Price, 1983; Shepherd, 2004; Wilson et al, 2015). While the peripheral sensory organs of the olfactory epithelium and vomeronasal organ initiate the uptake, different neurotransmitter systems of the main and accessory olfactory CNS serve to process the information and, modulate cortical and subcortical olfactory areas via feedback-regulation. We focused on all known cortical and subcortical olfactory areas and their receptor architecture in the mouse brain

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