Mild traumatic brain injury (mTBI) is a major health concern that affects millions of people worldwide. People who sustain multiple head injuries are at increased risk for chronic psychiatric morbidity, particularly in the dysregulation of emotional and social behaviors. Previous research has suggested that long-term negative effects on mood states and social functioning are related to dysfunction of brain reward and motivational circuits including the lateral habenula (LHb). However, the role of LHb dysfunction in mTBI-induced psychopathology remains unknown, and further research is needed to explore this possible connection.
A recent animal study investigated the effects of repeated mTBI on brain activity and behavior, and the potential therapeutic effects of inhibiting the LHb. The researchers also used electrophysiological techniques to study the spontaneous activity and synaptic function of LHb neurons. The study found that:
- MTBI increased spontaneous tonically active LHb neurons, but decreased bursting activity.
- MTBI diminished spontaneous glutamatergic and GABAergic synaptic activity onto LHb neurons.
- Synaptic excitation and inhibition (E/I) balance was shifted toward excitation through a greater suppression of GABAergic transmission.
- MTBI increased the latency in grooming behavior in the sucrose splash test.
- Inhibition of LHb activity was found to reverse mTBI-induced delays in grooming behavior.
This animal study investigated alterations in the LHb, a critical stress- and reward-related brain region. The findings suggest that mTBI-induced alterations in excitatory and inhibitory balance resulted in decreased GABAergic transmission and increased tonic activity of LHb neurons, contributing to motivational deficits in self-care and grooming behavior in male mice. The study provides the first evidence for persistent LHb neuronal dysfunction due to altered synaptic integration as causal neural correlates of dysregulated motivational states by mTBI and highlights the importance of understanding the underlying mechanisms of mTBI-induced negative affective states and the need for further research in this area.
Flerlage WJ, Langlois LD, Rusnak M, Simmons SC, Gouty S, Armstrong RC, Cox BM, Symes AJ, Tsuda MC, Nugent FS. Involvement of Lateral Habenula Dysfunction in Repetitive Mild Traumatic Brain Injury-Induced Motivational Deficits. Journal of Neurotrauma. (2023).