The Neurotransmitter Receptor Architecture of the Mouse Olfactory System

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.

A multifaceted architectural framework of the mouse claustrum complex

“…Conversely, IHC markers like calbindin‐D28 (CB), calretinin (CR), somatostatin (SST), myelin basic protein (MBP), and tyrosine hydroxylase show a paucity of labeling in the CL area that can also help define its borders (Barbier et al., 2017 ; Borroto‐Escuela & Fuxe, 2020 ; Celio, 1990 ; Davila et al., 2005 ; Druga et al., 2014 ; Graf et al., 2020 ; Marriott et al., 2021 ; Real et al., 2003 ; Wang et al., 2017 , 2023 ). The chemo‐architecture of the DEn is not as well characterized but shows an elevated expression of oxytocin and dopamine receptors (Biggs & Hammock, 2022 ; Lothmann et al., 2021 ; Yoshida et al., 1988 ). A complete characterization of all these markers is beyond the scope of this article, and instead we have selected a few markers, whose combined expression in the same tissue would yield a robust fiber‐ and cytoarchitectural basis for delineating the CLCX.…”