IntroductionEmotion is a complex, integrative response to changes in internal and external environments.1 Emotional flexibility — the capacity to dynamically regulate and adapt these responses — is fundamental for mental health and survival.2 Conversely, deficits in this adaptive capacity result in emotional rigidity, a hallmark of dysregulation that is strongly associated with psychiatric disorders such as depression and post-traumatic stress disorder (PTSD).3,4 Therefore, delineating the molecular and cellular mechanisms that govern the balance between emotional flexibility and rigidity is critical for elucidating the biological basis of resilience.5,6Neurovascular coupling (NVC), the core physiological foundation of blood oxygen level-dependent functional MRI (BOLD fMRI) signals, has long been categorized as a passive neural proxy.7,8,9,10 Clinical observations in the basolateral amygdala (BLA) — a pivotal hub for processing negative affect — reveal pervasive neurovascular dysregulation across diverse psychiatric landscapes.11 Specifically, exaggerated BOLD responses occur in PTSD, bipolar disorder, high body mass index (BMI), and cohorts exposed to early-life stress.8,12,13,14,15 In contrast, autosomal recessive Urbach-Wiethe disease, stemming from mutations in the ECM1 gene, is marked by a lack of hemodynamic responsiveness; such patients exhibit BLA vascular perturbations leading to localized calcification, alongside a selective deficit in fear perception when confronted with threat.16,17Consistent with this clinical phenotype, NVC impairments are recapitulated in animal models, where acute, chronic, and neuroendocrine stressors significantly impair NVC fidelity within stress-sensitive circuits.18,19,20 However, a fundamental question of causality remains: do these deficits merely reflect secondary consequences of neuronal dysfunction, or do they actively drive emotional pathology?Emerging evidence indicates that vascular-derived cues actively modulate diverse neural processes. For instance, nitric oxide generated during NVC promotes adult hippocampal neurogenesis,21 while vascular-derived nitric oxide depolarizes the membrane potential of the optic nerve.22 In the hypothalamus, salt-loading-induced vasoconstriction during NVC exerts positive feedback that enhances local vasopressin neuronal activity.23 Additionally, whole-cell patch recordings in brain slices demonstrate that altered parenchymal arteriolar tone modulates nearby neuronal firing, decreasing pyramidal neuron activity and increasing interneuron activity, with effects depending on a mechanosensitive cation channel.24 These observations imply that NVC possesses an intrinsic capacity, likely via chemical and/or mechanical cues, to actively regulate neural circuits, extending beyond its traditional role in metabolic support.25However, its potential as a real-time gatekeeper of emotional circuitry remains unexplored. To address this gap, we investigated NVC within the BLA as a model system. We hypothesized that BLA NVC functions as a critical regulatory checkpoint that calibrates the intensity of negative emotions, thereby maintaining emotional flexibility.26In this study, we employed a multidimensional emotion assessment framework combined with cell type-specific genetic manipulations and arteriolar optogenetics to demonstrate that NVC in the BLA actively and bidirectionally modulates emotional reactivity. In contrast to its lack of contribution in the somatosensory barrel cortex (S1BF), we found that neurovascular decoupling in the BLA precipitated emotional rigidity — a maladaptive state defined by a collapse in the dynamic range of emotional responses — manifesting as a distinctive biphasic dysregulation in which physiological and behavioral outputs were pathologically exaggerated under mild stress yet paradoxically blunted under intense stress. Mechanistically, we showed that this behavioral rigidity was underpinned by corresponding biphasic shifts in BLA neural activity across graded stressors. Notably, the enhanced NVC model conferred emotional resilience against chronic stress by normalizing BLA neural circuit activity. These findings establish NVC as an intrinsic regulatory gain controller in emotional processing and suggest that targeting circuit-specific neurovascular communication offers a novel therapeutic strategy for psychiatric dysregulation.ResultsValidation of a quantitative behavioral framework linking graded BLA activation to escalating spatial stress levelsTo dissect the neurovascular mechanisms actively modulating emotion, we first established a robust, quantifiable behavioral paradigm that scales linearly with stress intensity. We exposed male age-matched wild-type (WT) mice to contexts with graded anxiogenic potential for 15 min: the home cage (HC; minimal stress); the 40-cm, 35-cm, and 10-cm open field test (OFT; mild-to-moderate stress); and acute restraint stress (ARS; intense stress) (Fig. 1a).27,28,29,30,31 We verified BLA neuronal activation 90 min post-assay by assessing c-Fos expression (Fig. 1b). Immunofluorescence (IF) mapping revealed that c-Fos intensity increased in a stress-dependent manner (Fig. 1c). Crucially, this graded BLA activation was mirrored by a stepwise increase in defecation bouts (Fig. 1d), showing a robust linear correlation with BLA c-Fos intensity (R = 0.8160, P