The intercalated nuclear complex of the primate amygdala

Abstract

The organization of the inhibitory intercalated cell masses (IM) of the primate amygdala is largely unknown despite their key role in emotional processes. We studied the structural, topographic, neurochemical and intrinsic connectional features of IM neurons in the rhesus monkey brain. We found that the intercalated neurons are not confined to discrete cell clusters, but form a neuronal net that is interposed between the basal nuclei and extends to the dorsally-located anterior, central, and medial nuclei of the amygdala. Unlike the IM in rodents, which are prominent in the anterior half of the amygdala, the primate inhibitory net stretched throughout the antero-posterior axis of the amygdala, and was most prominent in the central and posterior extent of the amygdala. There were two morphologic types of intercalated neurons: spiny and aspiny. Spiny neurons were the most abundant; their somata were small or medium size, round or elongated, and their dendritic trees were round or bipolar, depending on location. The aspiny neurons were on average slightly larger and had varicose dendrites with no spines. There were three non-overlapping neurochemical populations of IM neurons, in descending order of abundance: 1. Spiny neurons that were positive for the striatal associated dopamine- and cAMP-regulated phosphoprotein (DARPP-32+); 2. Aspiny neurons that expressed the calcium-binding protein calbindin (CB); and 3. Aspiny neurons that expressed nitric oxide synthase (NOS+). The unique combinations of structural and neurochemical features of the three classes of IM neurons suggest different physiological properties and function. The three types of IM neurons were intermingled and likely interconnected in distinct ways, and were innervated by intrinsic neurons within the amygdala, or by external sources, in pathways that underlie fear conditioning and anxiety.

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

“…One group includes cells with darkly stained nuclei (oligodendrocytes and microglia), and the other group includes cells with lightly stained nuclei (neurons, astrocytes and endothelial cells). We previously used cellular features to estimate neuron and glial cell population in the cerebral cortex (García-Cabezas and Barbas, 2014) and the intercalated masses of the monkey amygdala where neurons and glial cell types could be distinguished with the same criteria used in the cortex (Zikopoulos et al, 2016). We have also used the cellular features that make up the algorithm to estimate the density of neurons in the gray matter of prefrontal cortices of the typical adult human brain and in individuals with autism (Zikopoulos and Barbas, 2010), as well as oligodendrocytes and other glial cells in the white matter below prefrontal cortices in the human brain at the electron microscopic level (Zikopoulos and Barbas, 2010).…”

Deconstructing white matter connectivity of human amygdala nuclei with thalamus and cortex subdivisions in vivo

“…In particular, separating the central from the cortical nucleus would merit further exploration. The intercalated nuclear complex of the amygdala, a group of inhibitory neurons, which form a net in between major amygdala nuclei, intrinsically regulate amygdala activity [Zikopoulos et al, ] and are critically involved in fear extinction [Likhtik et al, ] represent another important target for future research that may benefit from a more advanced amygdala parcellation method. However, while a recent study has proposed a probabilistic atlas of major nuclei based on high‐resolution group data [Tyszka and Pauli, ], a robust method for amygdala parcellation into smaller substructures on an individual level is still missing.…”

Specificity of Primate Amygdalar Pathways to Hippocampus

“…The predominant amygdalar innervation of SLM in anterior hippocampus coincides with terminations of perforant pathways from entorhinal cortex, noted for a role in affective contextual memory in rats, mice, and primates (Steward and Scoville, 1976;Witter and Amaral, 1991;Kjelstrup et al, 2002;Poppenk et al, 2013;Strange et al, 2014;Zeidman and Maguire, 2016). In contrast, amygdalar terminations in posterior hippocampus targeted the distal CA1 and proximal ProS, where neurons project out of the hippocampus (Rosene and Van Hoesen, 1977).…”

“…The neural basis of this process is likely mediated through pathways between the two structures, as shown in primates and rodents (Saunders et al, 1988;Cahill and McGaugh, 1998;Allsop et al, 2014;Felix-Ortiz and Tye, 2014;Redondo et al, 2014). The amygdala is one of only a few structures that has direct connections with the hippocampus, sharing privileged access with the entorhinal cortex, midline thalamic nuclei, and the septum in primates and rats (Witter and Amaral, 1991;Khakpai et al, 2013;Vertes et al, 2015;Eichenbaum, 2017).…”