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Updated: Feb 8, 2026

Quantification of Drosophila melanogaster Grooming Behavior for Evaluation of Excessive Grooming Phenotypes
Published on: March 21, 2025
Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in
Cindy M Pinhal1, Bastijn J G van den Boom2, Fabiana Santana-Kragelund1
1Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
Background:
Deep brain stimulation (DBS) is an effective treatment for patients with obsessive-compulsive disorder (OCD) that do not respond to conventional therapies. Although the precise mechanism of action of DBS remains unknown, modulation of activity in corticofugal fibers originating in the prefrontal cortex is thought to underlie its beneficial effects in OCD.
Methods:
To gain more mechanistic insight into DBS in OCD, we used Sapap3 mutant mice. These mice display excessive self-grooming and increased anxiety, both of which are responsive to therapeutic drugs used in OCD patients. We selected two clinically relevant DBS targets through which activity in prefronto-corticofugal fibers may be modulated: the internal capsule (IC) and the dorsal part of the ventral striatum (dVS).
Results:
IC-DBS robustly decreased excessive grooming, whereas dVS-DBS was on average less effective. Grooming was reduced rapidly after IC-DBS onset and reinstated upon DBS offset. Only IC-DBS was associated with increased locomotion. DBS in both targets induced c-Fos expression around the electrode tip and in different regions of the prefrontal cortex. This prefronto-cortical activation was more extensive after IC-DBS, but not associated with behavioral effects. Furthermore, we found that the decline in grooming cannot be attributed to altered locomotor activity and that anxiety, measured on the elevated plus maze, was not affected by DBS.
Conclusions:
DBS in both the IC and dVS reduces compulsive grooming in Sapap3 mutant mice. However, IC stimulation was more effective, but also produced motor activation, even though both DBS targets modulated activity in a similar set of prefrontal cortical fibers.
Insights
Deep brain stimulation (DBS) effectively reduces compulsive grooming in mice. Internal capsule stimulation was more effective than ventral striatum stimulation, offering insights into DBS mechanisms for obsessive-compulsive disorder (OCD).
Area of Science:
- Neuroscience
- Behavioral Science
Background:
- Deep brain stimulation (DBS) is a viable treatment for obsessive-compulsive disorder (OCD) refractory to traditional therapies.
- The exact mechanism of DBS in OCD remains unclear, but prefrontal cortex corticofugal fiber modulation is implicated.
Purpose of the Study:
- To investigate the mechanistic insights of DBS for OCD using Sapap3 mutant mice.
- To compare the efficacy of DBS targeting the internal capsule (IC) and dorsal ventral striatum (dVS) on compulsive behaviors.
Main Methods:
- Sapap3 mutant mice, exhibiting excessive self-grooming and anxiety, were used as a model for OCD.
- Deep brain stimulation (DBS) was applied to the internal capsule (IC) and dorsal ventral striatum (dVS).
- Behavioral changes (grooming, locomotion, anxiety) and neuronal activation (c-Fos expression) were assessed.
Main Results:
- Internal capsule DBS (IC-DBS) significantly reduced excessive grooming, while dorsal ventral striatum DBS (dVS-DBS) was less effective.
- Grooming reduction was rapid and reversible with IC-DBS; increased locomotion was also observed.
- Both DBS targets modulated prefrontal cortex activity, with more extensive activation following IC-DBS, but anxiety levels remained unaffected.
Conclusions:
- DBS in both IC and dVS reduces compulsive grooming in a mouse model of OCD.
- IC stimulation demonstrated higher efficacy in reducing grooming but also induced motor activation.
- Both targets modulate prefrontal cortical fibers, suggesting potential therapeutic pathways for OCD treatment.
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