Receptor-driven, multimodal mapping of the human amygdala

Abstract

The human amygdala consists of subdivisions contributing to various functions. However, principles of structural organization at the cellular and molecular level are not well understood. Thus, we re-analyzed the cytoarchitecture of the amygdala and generated cytoarchitectonic probabilistic maps of ten subdivisions in stereotaxic space based on novel workflows and mapping tools. This parcellation was then used as a basis for analyzing the receptor expression for 15 receptor types. Receptor fingerprints, i.e., the characteristic balance between densities of all receptor types, were generated in each subdivision to comprehensively visualize differences and similarities in receptor architecture between the subdivisions. Fingerprints of the central and medial nuclei and the anterior amygdaloid area were highly similar. Fingerprints of the lateral, basolateral and basomedial nuclei were also similar to each other, while those of the remaining nuclei were distinct in shape. Similarities were further investigated by a hierarchical cluster analysis: a two-cluster solution subdivided the phylogenetically older part (central, medial nuclei, anterior amygdaloid area) from the remaining parts of the amygdala. A more fine-grained three-cluster solution replicated our previous parcellation including a laterobasal, superficial and centromedial group. Furthermore, it helped to better characterize the paralaminar nucleus with a molecular organization in-between the laterobasal and the superficial group. The multimodal cyto- and receptor-architectonic analysis of the human amygdala provides new insights into its microstructural organization, intersubject variability, localization in stereotaxic space and principles of receptor-based neurochemical differences.

Neuronal types of the human cortical amygdaloid nucleus

“…It is also possible that the “pyramidal” and “pyramidal‐like” neurons described by Sims and Williams () and de Olmos () can be represented by the pyramidal‐like, angular, and/or triangular neurons classified apart here only after visualizing the dendritic features using the Golgi method results. The cell body of some fusiform neurons resembles the classification of “fork‐shaped” neurons in the dorsal part of the ventral cortical nucleus provided by Kedo et al (). A similar discrepancy in neuronal classification between Nissl staining and Golgi data occurred for the human MeA (Dall'Oglio et al, ).…”

“…Indeed, neuronal degeneration in the CoA and periamygdaloid cortex is evident in the course of the Alzheimer's disease (Schmidt, Martin, Lee, & Trojanowski, ). In addition, the superficial amygdaloid nuclei participate in the normal processing of emotional cues from speech prosody and fearful stimuli (Kedo et al, and references therein) and the elaboration of the arousal and valence of human facial expressions to guide social interactions (Goossens et al, ).…”

“…Currently, it is possible to consider that there are some similarities in the development of excitatory neurons in both the CoA and basolateral amygdaloid complex and the cerebral cortex, as identified by the expression of a specific telencephalic progenitor pool in mice (Hirata et al, ). In humans, the ventral cortical nucleus has an evident expression of AMPA and NMDA glutamate receptors, GABA B receptor and benzodiazepine binding sites, cholinergic muscarinic M 1 and M 3 receptors, (nor‐)adrenergic α 1 receptor, dopaminergic D 1 receptor, and serotoninergic 5‐HT 2 receptor (Kedo et al, ).…”

“…The sCLR is a controversial area in the human brain (Amaral et al, ; de Olmos, ; García‐Amado & Prensa, ; Gloor, ; Johnston, ; Kedo et al, ; Sorvari, Soininen, Paljärvi, Karkola, & Pitkänen, ; Yilmazer‐Hanke, ). The nomenclature and the exact location of each of its components are not quite congruent in the literature.…”

“…This reflects on the anatomical and cytoarchitectonic subdivisions proposed for the CoA and the adjacent periamygdaloid cortex. Besides the identification of superficial and deeper layers, the CoA was described as having (a) medial and lateral parts (Sims & Williams, ; see also García‐Amado & Prensa, and further references therein); (b) anterior (ACO) and posterior (PCO) subdivisions (Sorvari et al, ; Sorvari, Soininen, & Pitkänen, ); (c) dorsal and ventral parts in the ACO apart from the PCO (Mai, Majtanik, & Paxinos, ; Mai, Paxinos, & Voss, ); (d) dorsolateral and ventromedial subdivisions (Gloor, ); (e) ACO and PCO with dorsal and ventral subdivisions plus a marginal layer in both major parts (Ding et al, ); (f) ACO divided into dorsal and ventral parts whereas the ventral CoA was divided into rostral and caudal parts with superior, intermediate, and inferior components (de Olmos, ); or (g) PCO, as part of the amygdalohippocampal transition area, and the ventral cortical nucleus, with its parcellations, in the superficial group of the amygdaloid subdivision (Kedo et al, ).…”