RESUMEN
Acetylcholine is a robust neuromodulator of the limbic system and a critical regulator of arousal and emotions. The anterior cingulate cortex (ACC) and the amygdala (AMY) are key limbic structures that are both densely innervated by cholinergic afferents and interact with each other for emotional regulation. The ACC is composed of functionally distinct dorsal (A24), rostral (A32), and ventral (A25) areas that differ in their connections with the AMY. The structural substrates of cholinergic modulation of distinct ACC microcircuits and outputs to AMY are thought to depend on the laminar and subcellular localization of cholinergic receptors. The present study examines the distribution of muscarinic acetylcholine receptors, m1 and m2, on distinct excitatory and inhibitory neurons and on AMY-targeting projection neurons within ACC areas, via immunohistochemistry and injections of neural tracers into the basolateral AMY in adult rhesus monkeys of both sexes. We found that laminar densities of m1+ and m2+ expressing excitatory and inhibitory neurons depended on area and cell type. Among the ACC areas, ventral subgenual ACC A25 exhibited greater m2+ localization on presynaptic inhibitory axon terminals and greater density of m1+ and m2+ expressing AMY-targeting (tracer+) pyramidal neurons. These patterns suggest robust cholinergic disinhibition and potentiation of amygdalar outputs from the limbic ventral ACC, which may be linked to the hyperexcitability of this subgenual ACC area in depression. These findings reveal the anatomical substrate of diverse cholinergic modulation of specific ACC microcircuits and amygdalar outputs that mediate cognitive-emotional integration and dysfunctions underlying stress and affective disorders.
Asunto(s)
Giro del Cíngulo , Macaca mulatta , Animales , Giro del Cíngulo/metabolismo , Giro del Cíngulo/fisiología , Masculino , Femenino , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M1/metabolismo , Red Nerviosa/metabolismo , Red Nerviosa/fisiología , Acetilcolina/metabolismo , Vías Nerviosas/fisiología , Vías Nerviosas/metabolismo , Neuronas/metabolismo , Neuronas/fisiologíaRESUMEN
The stria terminalis (ST) is a major bidirectional fiber tract anchored in the amygdala and bed nucleus (BNST). Extensive investigations in rodents report a complex arrangement of neurochemically diverse neurons within the ST, but fewer data are available for non-human primates. Given the functional importance of the ST, we investigated its microarchitecture in one newborn, four infant, and two adult macaque brains, by parallel immunocytochemical series for cells or fibers. Main results are as follows: (1) The pan-neuronal marker NeuN shows scattered neurons and small neuronal clusters in both the dorsal and ventral ST, but more numerous dorsally; (2) smaller neuronal subpopulations are labeled by calretinin (CR), neuropeptide Y (NPY), calbindin (CB), and somatostatin (SOM), of which the CR + neurons are the most numerous; (3) the infant brains on average have more neurons in the ST than the adult brains, but across our sample, there is notable individual variability; and (4) fiber architectonics have a complex organization, which can be referenced to myelin-poor or myelin-dense zones. Myelin-poor zones coincide with concentrations of fibers positive for CB, CR, or tyrosine hydroxylase (TH). Neurons have been reported in other white matter domains (e.g., anterior commissure, corpus callosum, cingulum bundle, and subcortical white matter). Like these, at least some neurons within the ST may give rise to long-distance connections, and/or participate in more local functions, such as vascular regulation or axon guidance/maintenance.