A groundbreaking study has unveiled a novel approach to dampen the consolidation of conditioned fear memories by targeting a critical neurocircuitry pathway in the mouse brain. This innovative research, conducted by Wang, Z., Liu, Z., Yu, Y., and colleagues, reveals that stellate ganglion block (SGB) effectively inhibits the neural communication between the locus coeruleus (LC) and the basolateral amygdala (BLA), a vital circuit involved in fear memory consolidation. Published in Translational Psychiatry in 2025, these findings could have profound implications for developing new interventions in fear-related disorders such as post-traumatic stress disorder (PTSD).
The consolidation of fear memory represents a fundamental process by which the brain stabilizes and stores fearful experiences. This process enables an organism to adapt and respond to threats but can become maladaptive in pathological states, where fear memories persist and intrude uncontrollably. The involvement of the LC-BLA neural circuit has previously been implicated in modulating emotional memories, given the LC’s role as a primary source of noradrenergic input to various brain regions, including the amygdala, which orchestrates fear processing. By strategically inhibiting this pathway, the research team sought to elucidate mechanistic insights and therapeutic targets to mitigate conditioned fear memory consolidation.
Stellate ganglion block is a clinical technique traditionally used to alleviate sympathetic nervous system hyperactivity, typically applied for pain syndromes and vascular conditions. It involves the administration of local anesthetics to the stellate ganglion, a sympathetic nerve ganglion located in the neck. This study pioneers the application of SGB to modulate central fear circuits by interrupting the sympathetic outflow that influences LC activity. Experiments demonstrated that SGB inhibited the excitatory neural transmission from the LC to the BLA, thereby preventing the strengthening of the synaptic connections essential for fear memory consolidation.
In the experimental framework, mice underwent a classical fear conditioning protocol wherein a neutral stimulus was paired with an aversive foot shock, leading to the formation of a conditioned fear response. Administration of the stellate ganglion block immediately following conditioning notably reduced the expression of fear behaviors during subsequent memory recall tests. Interestingly, this intervention did not impair the acquisition of the fear memory itself, indicating a specific disruption in the consolidation phase without affecting initial learning.
Electrophysiological recordings and neural circuit mapping provided compelling evidence that SGB dampened the noradrenergic output from the LC, resulting in diminished neuronal excitability within the BLA. This neurochemical disruption translated into decreased synaptic plasticity markers, including reduced long-term potentiation, which underlies the encoding and reinforcement of emotional memories. These results emphasize the critical role played by LC-mediated noradrenaline release in modulating amygdala-dependent fear memories.
Further molecular analysis revealed that blocking the LC-to-BLA pathway affected downstream intracellular signaling cascades responsible for memory stabilization. Among these, a marked reduction in cAMP response element-binding protein (CREB) phosphorylation was observed, a transcription factor integral to gene expression necessary for long-term memory consolidation. By attenuating this cascade, SGB effectively interfered with the molecular machinery that supports the transition of labile fear memories into enduring, consolidated forms.
Importantly, the research team also evaluated the temporal window within which stellate ganglion blockade exerted its effects. Delivering the block during critical periods immediately following fear conditioning resulted in pronounced memory attenuation, whereas delayed administration showed diminished efficacy. This timing-dependence underscores the importance of early intervention targeting sympathetic modulation to disrupt fear memory consolidation pathways.
The translational significance of these findings cannot be overstated. PTSD and related anxiety disorders are characterized by intrusive and persistent fear memories that significantly impair quality of life. Current treatment modalities, including pharmacotherapy and behavioral therapy, often yield limited success and can be associated with adverse effects. Targeting the LC-BLA circuit through SGB presents a promising, minimally invasive strategy for modifying pathological fear memories at a neurobiological level.
Moreover, this study bridges a crucial gap between peripheral nervous system interventions and central brain mechanisms. By demonstrating that a peripheral nerve block can influence deep brain circuits involved in emotional memory, it opens avenues for novel therapeutic paradigms leveraging autonomic modulation to alter brain function. This integrative approach could revolutionize how neuropsychiatric conditions are managed in clinical settings.
The researchers emphasize that while these findings in mice are encouraging, further investigations are essential to evaluate safety, optimal dosing, and timing parameters in humans. The adaptability and complexity of human fear circuits necessitate carefully designed clinical trials to translate these preclinical results into effective treatments. Nonetheless, the mechanistic insights provided here lay a robust foundation for such future endeavors.
From a neuroscience perspective, dissecting the LC-BLA interaction provides a deeper understanding of how noradrenergic signaling shapes emotional memory processes. The locus coeruleus, with its widespread projections, acts as a hub modulating arousal and attention, thereby influencing memory encoding and consolidation. Targeting this hub via interventions like SGB allows for selective modulation of pathological memory circuits without broadly suppressing brain function.
This study also invites further exploration into the role of sympathetic nervous system inputs on central emotional processes, challenging the traditional dichotomy between peripheral and central nervous system functions. The dynamic crosstalk between these systems appears to underpin fundamental aspects of memory and emotion, suggesting new biological targets and treatment strategies.
Moreover, the methodological innovations combining behavioral paradigms, electrophysiology, molecular biology, and neuroanatomical tracing in this study set a high standard for future research. The multidisciplinary approach enriches our understanding of the cellular and circuit-level mechanisms governing fear memory and highlights the power of integrative neuroscience research.
The implications of this research extend beyond fear memory into potentially other domains involving emotional processing and maladaptive behaviors. Conditions such as addiction, chronic stress, and mood disorders might similarly benefit from strategies targeting peripheral autonomic pathways to recalibrate central emotional networks.
In conclusion, the pioneering work by Wang and colleagues presents a compelling case for utilizing stellate ganglion block as a novel intervention to disrupt the consolidation of conditioned fear memory by inhibiting the locus coeruleus to basolateral amygdala neural circuit. This approach combines clinical feasibility with mechanistic precision, offering hope for improved therapeutic options for fear-based neuropsychiatric disorders. Continued research in this promising direction is eagerly anticipated by the neuroscience and clinical communities alike.
Subject of Research: Inhibition of fear memory consolidation via neural circuit modulation involving stellate ganglion block affecting the locus coeruleus to basolateral amygdala pathway.
Article Title: Stellate ganglion block diminishes consolidation of conditioned fear memory in mice by inhibiting the locus coeruleus to the basolateral amygdala neural circuit.
Article References:
Wang, Z., Liu, Z., Yu, Y. et al. Stellate ganglion block diminishes consolidation of conditioned fear memory in mice by inhibiting the locus coeruleus to the basolateral amygdala neural circuit. Transl Psychiatry 15, 172 (2025). https://doi.org/10.1038/s41398-025-03383-7
Image Credits: AI Generated
