ABSTRACT
BACKGROUND: Chronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The behavioral sequelae of stress correlate with dendritic hypertrophy and glutamate-related synaptic remodeling at basolateral amygdala projection neurons (BLA PNs). Yet, though BLA PNs are functionally heterogeneous with diverse corticolimbic targets, it remains unclear whether stress differentially impacts specific output circuits. METHODS: Confocal imaging was used to reconstruct the morphology of mouse BLA PNs with the aid of retrograde tracing and biocytin staining. The synaptic activity in these neurons was measured with in vitro electrophysiology, and anxiety-like behavior of the mice was assessed with the elevated plus maze and open field test. RESULTS: Chronic restraint stress (CRS) produced dendritic hypertrophy across mouse BLA PNs, regardless of whether they did (BLAâdorsomedial prefrontal cortex [dmPFC]) or did not (BLAâdmPFC) target dmPFC. However, CRS increased the size of dendritic spine heads and the number of mature, mushroom-shaped spines only in BLAâdmPFC PNs, sparing neighboring BLAâdmPFC PNs. Moreover, the excitatory glutamatergic transmission was also selectively increased in BLAâdmPFC PNs, and this effect correlated with CRS-induced increases in anxiety-like behavior. Segregating BLAâdmPFC PNs based on their targeting of ventral hippocampus (BLAâventral hippocampus) or nucleus accumbens (BLAânucleus accumbens) revealed that CRS increased spine density and glutamatergic signaling in BLAâventral hippocampus PNs in a manner that correlated with anxiety-like behavior. CONCLUSIONS: Chronic stress caused BLA PN neuronal remodeling with a previously unrecognized degree of circuit specificity, offering new insight into the pathophysiological basis of depression, anxiety disorders, and other stress-related conditions.