Molecular diversity and functional dynamics in the central amygdala

Abstract

The central amygdala (CeA) is crucial in integrating sensory and associative information to mediate adaptive responses to emotional stimuli. Recent advances in genetic techniques like optogenetics and chemogenetics have deepened our understanding of distinct neuronal populations within the CeA, particularly those involved in fear learning and memory consolidation. However, challenges remain due to overlapping genetic markers complicating neuron identification. Furthermore, a comprehensive understanding of molecularly defined cell types and their projection patterns, which are essential for elucidating functional roles, is still developing. Recent advancements in transcriptomics are starting to bridge these gaps, offering new insights into the functional dynamics of CeA neurons. In this review, we provide an overview of the expanding genetic markers for amygdala research, encompassing recent developments and current trends. We also discuss how novel transcriptomic approaches are redefining cell types in the CeA and setting the stage for comprehensive functional studies.

Keywords: amygdala; cell types; fear learning; memory; transcriptomics.

FIGURE 1

Genetic markers and developmental origins in the amygdala of mice. (A) The critical genetic markers that reveal the developmental origins of the amygdala neurons. The majority of the principal neurons in the LA and anterior BLA originate from Dbx1⁺ neurons in the lateral and basal pallial units of embryonic mice brains. More Emx1⁺ neurons appear in the posterior BLA (BLAp), while the Dbx1⁺ and Emx1⁺ neurons are generally intermixed in the LA and BLA. The CeA neurons are marked by Dlx5, suggesting their striatal origin, and are distinct in lacking pallial markers. The Isl1⁺ neurons, predominantly found in the CeM, are derived from the ventral part of the lateral ganglionic eminence (vLGE). In contrast, the Pax6⁺ neurons, which are more prevalent in the CeC and CeL, originate from the dorsal part of the LGE (dLGE). (B) Prominent genetic markers in the BLA and the CeA of adult mice. Zfhx3 expression is enriched in the CeA, distinguishing it from adjacent brain structures. PKC-δ/Calcrl and CRF markers are mostly found in the CeL and CeC, while SOM neurons reside in the CeL and the CeM. Tac2 neurons are mostly present in the CeM, with some distribution in the CeL. Glutamatergic neurons in the LA and BLA are predominantly identified by Slc17a7 (vGlut1) and Slc17a6 (vGlut2) markers, with Slc17a7⁺Slc17a6⁺ double-positive neurons confined to the LA. Ddit4l and Myl4 expression is primarily observed in the LA. In contrast, marker genes such as Cplx1 and Lynx1 were generally located in the basal amygdala (BA), with minimal overlap with the Ddit4l⁺ and Myl4⁺ neurons. Fezf2 and Rspo2 expressing neurons are highly co-localized in the anterior part of the BLA, and these neurons have been implicated in a role in positive or negative emotional responses dependent on their projections.