 |
| This brain image illustrates the circuit connection between regions of the amygdala (in red) and the dorsolateral striatum in a model of obsessive-compulsive disorder. Image Credit: Zachary Hobel using Brainrender |
Scientific Frontline: Extended "At a Glance" Summary: Brain Circuit Discovered in Obsessive-Compulsive Disorder (OCD)
The Core Concept: Researchers have identified a specific neural circuit connecting the amygdala to the dorsolateral striatum (DLS) that amplifies sensory-evoked behaviors and is hyperactive in a murine model of obsessive-compulsive disorder (OCD).
Key Distinction/Mechanism: Unlike previous research focusing broadly on brain regions, this study isolates a discrete connection originating from a small population of amygdala neurons that directly projects to the DLS, demonstrating that stimulation of this pathway prolongs habitual responses to sensory stimuli even after the initial trigger is removed.
Major Frameworks/Components:
- The Amygdala: The brain region responsible for processing emotionally salient experiences, such as fear and anxiety.
- The Dorsolateral Striatum (DLS): The brain region associated with the execution of habitual and automatic behaviors.
- Synaptic Plasticity: The circuit amplifies and promotes the strengthening of other inputs to the DLS, specifically those encoding sensory-evoked behaviors.
- Murine Model: The research utilized mice, establishing that chronic inhibition of this specific amygdala-DLS circuit prevents OCD-like compulsive behaviors.
Branch of Science: Neurobiology, Neuroscience, Psychology, Psychiatry.
Future Application: These findings offer a novel target for the development of precise, localized neuromodulation or pharmacological therapies to treat OCD, moving beyond broad-spectrum psychotherapies and current medications.
Why It Matters: Identifying the exact neuronal circuitry underlying compulsive behavior provides a critical mechanistic explanation for how normal, sensory-cued actions transform into pathological compulsions, paving the way for targeted treatments for individuals with OCD.
Treatment for obsessive-compulsive disorder (OCD)—a mental health condition characterized by distressing, uncontrollable thoughts accompanied by repetitive behaviors—has historically centered on psychotherapy and medications to curb symptoms. New research identifying a previously unknown brain circuit involved in the OCD process could be a key step toward developing treatments that directly target certain brain regions to better control the condition.
Published early online in the journal Neuron and led by Joshua L. Plotkin, associate professor in the Department of Neurobiology and Behavior at the Renaissance School of Medicine (RSOM) at Stony Brook University, the research is based on a murine model. While the full capacity of a human brain differs significantly from that of a mouse, the two share strikingly similar structures and regional organizational principles.
This work involved using sensory stimuli to prompt behavioral actions in mice. During experimentation, Plotkin and his colleagues focused on two areas of the brain: the amygdala, a brain region that processes emotionally important experiences such as fear and anxiety, and the dorsolateral striatum (DLS), a region important for habitual and automatic behaviors.
The research team discovered that the amygdala directly connects to and influences the DLS, a connection not identified in previous research because it originates from only a small number of amygdala neurons—a scenario that is easy to overlook.
By using new imaging tools to functionally map brain circuits at the single-synapse level, Zachary Hobel, the study’s first author and a postdoctoral fellow in the Department of Neurobiology and Behavior, found that although it is small, the amygdala-DLS connection can have an outsized influence over the DLS. Experimental measures and neuronal models confirmed that this connection amplifies and promotes the synaptic plasticity of other inputs to the DLS—inputs that are likely to encode sensory-evoked behaviors.
The team found that repeatedly stimulating inputs from the amygdala to the DLS amplifies sensory-evoked behaviors, an effect that persisted long after the stimulation ended. Specifically, placing a droplet of water on a mouse’s nose prompted the animal to groom its face. When researchers stimulated the amygdala-to-DLS circuit while the mouse experienced the water droplet, the water subsequently caused the mouse to groom for much longer, even after the sensation and brain stimulation had stopped. Remarkably, the mouse continued to respond more strongly to the water even after the experimental pairing ended.
The researchers further demonstrated that this circuit is stronger, more active, and abnormally regulated in a mouse model of OCD. Therefore, by chronically inhibiting the amygdala in these mice, the researchers prevented OCD-like behavior—a key finding.
“Our study reveals a clear mechanism through which emotionally important experiences may strengthen the connection between sensory cues and actions, and this potentially helps explain how otherwise normal behaviors can be transformed into compulsive behaviors,” summarized Plotkin, the corresponding author and a researcher affiliated with Stony Brook’s Center for Nervous System Disorders.
Plotkin pointed out that mice serve as a strong model of OCD, as they respond to the same common medications used to treat humans with the disorder. He cautioned that the exact neuronal connections and dysfunctions altered or corrected by OCD treatments are not fully known, and the specific brain connections and processes underlying OCD are complex. However, the authors concluded that the findings provide important insights into the underpinnings of OCD-like behaviors and identify specific brain circuit dysfunctions—advances that provide researchers with new, more precise targets for OCD treatments.
Reference material: What Is: Obsessive-Compulsive Disorder
Funding: Funding for this work included support from several federal agencies: the National Institutes of Health’s (NIH) National Institute of Neurological Disorders and Stroke, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute of Mental Health.
Published in journal: Neuron
Title: A basolateral amygdala to dorsolateral striatum projection modulates stimulus-evoked motor behavior
Authors: Zachary B. Hobel, Taryn R. Brechbill, Adelis M. Cruz, Lu-Tang Yang, Kimberly Jimenez, Brandon Wu, Qinlin Liu, Sasha B. Kirsch, Nicole J. Fernandes, Roland Bock, Veronica A. Alvarez, Kim T. Blackwell, and Joshua L. Plotkin
Source/Credit: Stony Brook University
Edited by: Scientific Frontline
Reference Number: ns092926_01