Amygdala Intercalated Cells: Gate Keepers and Conveyors of Internal State to the Circuits of Emotion

Abstract

Generating adaptive behavioral responses to emotionally salient stimuli requires evaluation of complex associations between multiple sensations, the surrounding context, and current internal state. Neural circuits within the amygdala parse this emotional information, undergo synaptic plasticity to reflect learned associations, and evoke appropriate responses through their projections to the brain regions orchestrating these behaviors. Information flow within the amygdala is regulated by the intercalated cells (ITCs), which are densely packed clusters of GABAergic neurons that encircle the basolateral amygdala (BLA) and provide contextually relevant feedforward inhibition of amygdala nuclei, including the central and BLA. Emerging studies have begun to delineate the unique contribution of each ITC cluster and establish ITCs as key loci of plasticity in emotional learning. In this review, we summarize the known connectivity and function of individual ITC clusters and explore how different neuromodulators conveying internal state act via ITC gates to shape emotionally motivated behavior. We propose that the behavioral state-dependent function of ITCs, their unique genetic profile, and rich expression of neuromodulator receptors make them potential therapeutic targets for disorders, such as anxiety, schizophrenia spectrum, and addiction.

Microglia maintain structural integrity during fetal brain morphogenesis

“…Indeed, even in juvenile mice prenatally exposed to PLX3397 which display more transient lesions, we observed a disorganization of an axonal tract abutting the CSA, a capsule that conveys inputs to the Am, an essential brain structure which dysregulation is linked to neurodevelopmental disorders. 73 , 74 , 75 Both axonal tracts and Foxp2-positive inhibitory interneurons, important to gate inputs to the Am, 76 , 77 , 78 were disorganized ( Figures S6 A and S6B). Electrophysiological slice recordings in adult mice revealed that morphological deficits correlated with a consistent imbalance of inhibition/excitation (I/E) responses of Am pyramidal neurons following capsule stimulation ( Figure S6 C).…”

Anatomical Connectivity of the Intercalated Cells of the Amygdala

“…Important findings in this work include what was not observed. For instance, projections from the BLA to the ITCs is a commonly discussed synapse in ITC field (Asede et al, 2022, Palomares-Castillo et al, 2012, however our rabies tracing showed very little input from the BLA to ITCs, indicating that this connection reflects a minor subpopulation and that the ITCs likely serve broader functions than currently known or suggested. Instead, based on density of presynaptic regions, ITCs are more likely driven by cortical and thalamic nuclei that may present an unremarked confound in BLA-ITC studies.…”

Lateral Septal Circuits Govern Schizophrenia-Like Effects of Ketamine on Social Behavior

“…Since mice rely heavily on olfaction to navigate their environment, olfactory areas are expected to play an important role in social recognition. The IA consists of clusters of GABAergic neurons surrounding that basolateral nuclear complex (BNC) of the amygdala which are thought to mediate fear extinction by inhibiting amygdalar outputs to the hypothalamic and brainstem circuits [76][77][78]. These IA neurons receive excitatory inputs from the infralimbic cortex (IL) and BNC that presumably activate this fear extinction circuit [79].…”