Tripartite extended amygdala - basal ganglia CRH circuit drives arousal and avoidance behaviour

Abstract

An adaptive stress response involves various mediators and circuits orchestrating a complex interplay of physiological, emotional and behavioural adjustments. We identified a population of corticotropin-releasing hormone (CRH) neurons in the lateral part of the interstitial nucleus of the anterior commissure (IPACL) - a subdivision of the extended amygdala, which exclusively innervate the substantia nigra (SN). Specific stimulation of this circuit elicits arousal and avoidance behaviour contingent on CRH receptor 1 (CRHR1) located at axon terminals in the SN, which originate from external globus pallidus (GPe) neurons. The neuronal activity prompting the observed behaviour is shaped by IPACLCRH and GPeCRHR1 neurons coalescing in the SN. These results delineate a novel tripartite CRH circuit functionally connecting extended amygdala and basal ganglia nuclei to drive arousal and avoidance behaviour.

Hypothalamic CRH neurons in stress induced psychopathology: revaluation of endocrine and neural mechanisms

“…Rabies/dual label with CRH NAcC (Dedic et al, 2018) BNST (Dedic et al, 2018) Thalamus (Dedic et al, 2018) BLA and LA (Dedic et al, 2018) PAG (Dedic et al, 2018) Hypothalamus (unspecified) (Dedic et al, 2018) PVN (Jiang et al, 2018;Ramot et al, 2017) (Jiang et al, 2018) (project to CRFR1 neurons) LH (Ono et al, 2020) (Fuzesi et al, 2016;Ono et al, 2020) (Ono et al,: ORX/HCRT neurons) (Fuzesi et al, 2016) overlap with ME projections (Li et al, 2020;Saito et al, 2018) (project to ORX/HCRT neurons) ME (Dedic et al, 2018) (Reyes et al, 2005) *distinct from VTA projections (Fuzesi et al, 2016) overlap with LH projections VTA (Dedic et al, 2018) (Jiang et al, 2021;Rodaros et al, 2007) SN (Chang et al, 2022) preprint Habenular (Ono et al, 2020) LC (Ono et al, 2020) (Reyes et al, 2005) *distinct from ME projections NST (Ono et al, 2020) Raphe (Ono et al, 2020) GPe (Hunt et al, 2018)…”

“…Projections to regions within the basal ganglia circuitry have emerged as a key target of PVN CRH synaptic connections, including the globus pallidus externa (GPe) of the indirect pathway (Hunt et al, 2018), the ventral tegmental area (VTA) (Jiang et al, 2021;Rodaros et al, 2007), and more recent evidence for inputs to the substantia nigra [SN; preprint from (Chang et al, 2022)]. PVN CRH projections to these targets may influence processes such as action selection and coordination, decision making and reward processing.…”