Neuronal localization of m1 muscarinic receptor immunoreactivity in the monkey basolateral amygdala

Abstract

The basolateral nuclear complex (BNC) of the amygdala plays an important role in the generation of emotional/motivational behavior and the consolidation of emotional memories. Activation of M1 cholinergic receptors (M1Rs) in the BNC is critical for memory consolidation. Previous receptor binding studies in the monkey amygdala demonstrated that the BNC has a high density of M1Rs, but did not have sufficient resolution to identify which neurons in the BNC expressed them. This was accomplished in the present immunohistochemical investigation using an antibody for the m1 receptor (m1R). Analysis of m1Rs in the monkey BNC using immunoperoxidase techniques revealed that their expression was very dense in the BNC, and suggested that virtually all of the pyramidal projection neurons (PNs) in all of the BNC nuclei were m1R‐immunoreactive (m1R+). This was confirmed with dual‐labeling immunofluorescence using staining for calcium/calmodulin‐dependent protein kinase II (CaMK) as a marker for BNC PNs. However, additional dual‐labeling studies indicated that one‐third of inhibitory interneurons (INs) expressing glutamic acid decarboxylase (GAD) were also m1R+. Moreover, the finding that 60% of parvalbumin (PV) immunoreactive neurons were m1R+ indicated that this IN subpopulation was the main GAD+ subpopulation exhibiting m1R expression. The cholinergic innervation of the amygdala is greatly reduced in Alzheimer's disease and there is currently considerable interest in developing selective M1R positive allosteric modulators (PAMs) to treat the symptoms. The results of the present study indicate that M1Rs in both PNs and INs in the primate BNC would be targeted by M1R PAMs.

Functional neuroanatomy of basal forebrain projections to the basolateral amygdala: Transmitters, receptors, and neuronal subpopulations

“…The somata of very few glutamic acid decarboxylase (GAD)‐positive GABAergic INs in the BNC are M1R+, and the few that are have extremely light M1R‐ir. Likewise, most M1R+ neurons in the monkey BNC are CaMK+ PNs, but in the monkey, one‐third of inhibitory INs expressing GAD are also M1R+ (McDonald & Mott, 2021). Moreover, the finding that 60% of PV+ neurons in the monkey BNC are M1R+ indicates that this IN subpopulation is the main GABAergic subpopulation exhibiting M1R expression (McDonald & Mott, 2021).…”