Secretagogin marks amygdaloid PKCδ interneurons and modulates NMDA receptor availability

Abstract

The perception of and response to danger is critical for an individual’s survival and is encoded by subcortical neurocircuits. The amygdaloid complex is the primary neuronal site that initiates bodily reactions upon external threat with local-circuit interneurons scaling output to effector pathways. Here, we categorize central amygdala neurons that express secretagogin (Scgn), a Ca2+-sensor protein, as a subset of protein kinase Cδ (PKCδ)+ interneurons, likely “off cells.” Chemogenetic inactivation of Scgn+/PKCδ+ cells augmented conditioned response to perceived danger in vivo. While Ca2+-sensor proteins are typically implicated in shaping neurotransmitter release presynaptically, Scgn instead localized to postsynaptic compartments. Characterizing its role in the postsynapse, we found that Scgn regulates the cell-surface availability of NMDA receptor 2B subunits (GluN2B) with its genetic deletion leading to reduced cell membrane delivery of GluN2B, at least in vitro. Conclusively, we describe a select cell population, which gates danger avoidance behavior with secretagogin being both a selective marker and regulatory protein in their excitatory postsynaptic machinery.

Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns

“…Secretagogin is also expressed in neuroendocrine cells where it likely regulates exocytosis and hormone release [ 33 , 34 ]. Concordantly, it is also involved in danger avoidance behavior through the control of post synaptic cell surface availability of NMDA receptors in the central amygdala [ 35 ]. We are not aware, however, of published reports examining the relation between induced changes in secretagogin expression and lifespan or longevity.…”

Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns

“…NMDA receptors in the central amygdala 34 . We are not aware, however, of published reports examining the relation between induced changes in secretagogin expression and lifespan or longevity.…”

Mapping the brain in the twenty‐first century: Extrahypothalamic projections of TRH neurones

“…As the authors suggest, viral delivery of optogenetic or chemogenetic constructs into chemically engineered, that is, Onecut3-iCre, mice would allow us to study the role of this newly discovered cell population in vivo. 10 Dysfunction of Onecut3 + neurones or that of their circuit could be approached by Cre-dependent RNAimediated gene silencing. 11 The gates are open, and the path to a new chapter of brain neuroanatomy invites us for an eternal quest for knowledge.…”

“…To answer these questions, detailed behavioral and physiological experiments are needed, which aim the investigated Onecut3 + populations of the different brain locations. As the authors suggest, viral delivery of optogenetic or chemogenetic constructs into chemically engineered, that is, Onecut3 ‐iCre, mice would allow us to study the role of this newly discovered cell population in vivo 10 . Dysfunction of Onecut3 + neurones or that of their circuit could be approached by Cre‐dependent RNAi‐mediated gene silencing 11 .…”