ABSTRACT
Fear is essential for survival, but excessive anxiety behavior is debilitating. Anxiety disorders affecting millions of people are a global health problem, where new therapies and targets are much needed. Deep brain stimulation (DBS) is established as a therapy in several neurological disorders, but is underexplored in anxiety disorders. The lateral hypothalamus (LH) has been recently revealed as an origin of anxiogenic brain signals, suggesting a target for anxiety treatment. Here, we develop and validate a DBS strategy for modulating anxiety-like symptoms by targeting the LH. We identify a DBS waveform that rapidly inhibits anxiety-implicated LH neural activity and suppresses innate and learned anxiety behaviors in a variety of mouse models. Importantly, we show that the LH DBS displays high temporal and behavioral selectivity: Its affective impact is fast and reversible, with no evidence of side effects such as impaired movement, memory loss, or epileptic seizures. These data suggest that acute hypothalamic DBS could be a useful strategy for managing treatment-resistant anxiety disorders.
Subject(s)
Anxiety Disorders , Deep Brain Stimulation , Hypothalamic Area, Lateral , Animals , Anxiety Disorders/therapy , Deep Brain Stimulation/methods , Mice , Orexins/antagonists & inhibitors , Orexins/physiologyABSTRACT
Novel technology and innovative stimulation paradigms allow for unprecedented spatiotemporal precision and closed-loop implementation of neurostimulation systems. In turn, precise, closed-loop neurostimulation appears to preferentially drive neural plasticity in motor networks, promoting neural repair. Recent clinical studies demonstrate that electrical stimulation can drive neural plasticity in damaged motor circuits, leading to meaningful improvement in users. Future advances in these areas hold promise for the treatment of a wide range of motor systems disorders.
