Elsevier

Neuroscience

Volume 180, 28 April 2011, Pages 222-228
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Lesions of the dorsomedial striatum disrupt prepulse inhibition

https://doi.org/10.1016/j.neuroscience.2011.01.041Get rights and content

Abstract

Prepulse inhibition (PPI) of startle is an experimentally tractable measure of sensorimotor gating that can be readily evaluated in mice, rats, monkeys, and humans. PPI is the inhibitory effect of a low-intensity stimulus, the prepulse, on the startle response to a subsequent high-intensity stimulus. PPI has garnered great interest as a marker of clinically relevant information processing abnormalities, because it is impaired in such neuropsychiatric conditions as schizophrenia, Tourette syndrome, and obsessive compulsive disorder (OCD). Pathology of the basal ganglia has been described in all three of these disorders, and it is therefore of great interest to determine the role of the basal ganglia in PPI. Previous work in rats described a PPI deficit after excitotoxic ventral striatal lesions and a more subtle attenuation after caudodorsal lesion, but no effect of other large lateral dorsal lesions. However, previous studies have not specifically investigated the role of the dorsomedial striatum in PPI. We investigated this issue using excitotoxic lesions in mice. We describe a marked reduction in PPI, at a variety of prepulse intensities, after bilateral lesions of dorsomedial striatum. There was no effect of lesion on baseline startle or habituation. In contrast, comparably sized lesions of the central dorsal striatum had no effect on PPI. These results reveal a role for the dorsomedial striatum in prepulse inhibition, which may have relevance for the abnormalities observed in this region in such disorders as Tourette syndrome and OCD.

Highlights

▶Prepulse inhibition (PPI) is impaired in numerous neuropsychiatric disorders. ▶Several conditions with impaired PPI involve pathology of the striatum. ▶We found that excitoxic lesions of the dorsomedial striatum impaired PPI. ▶Comparable lesions of the adjacent central dorsal striatum had no effect on PPI. ▶These data reveal a specific contribution of the dorsomedial striatum to PPI.

Section snippets

Subjects

All experiments were conducted under the supervision of the Yale University Institutional Animal Care and Use Committee (Animal Welfare Assurance Number A3230-1). Food (standard laboratory chow) and water were available ad libitum. A total of 70 adult male C57Bl/6J mice were used in the study. Mice were 8–10 weeks old at the time of surgery and 14–16 weeks old at the time of testing. All animals were used in a water maze experiment (as in Lee et al., 2008) prior to PPI testing. All efforts were

Dorsomedial lesions of the striatum impair PPI

Excitotoxic lesions of the dorsomedial striatum were produced by stereotaxic infusion of NMDA (see Experimental procedures); control mice received identical infusions of normal saline, and the experimenter was blind to lesion condition. PPI was measured with prepulses 6, 12, and 16 dB above background using standard methods, as previously described (Geyer and Swerdlow, 2001).

RM-ANOVA of %PPI with a 100 ms prepulse-pulse interval showed significant main effects of lesion (RM-ANOVA: F[1,30]=5.74,

Discussion

Neuropsychiatric disorders such as schizophrenia, Tourette syndrome, and obsessive compulsive disorder are characterized by a loss in the normal ability to suppress or “gate” irrelevant information from external or internal sources (McGhie and Chapman, 1961, Schall et al., 1996, Swerdlow and Sutherland, 2005). PPI is a widely studied experimental measure of sensorimotor gating that is used as a simplified model of this process; PPI is impaired in all three disorders (Smith and Lees, 1989,

Conclusion

Our results showed that disruption of the medial aspects of the striatum in mice caused significant deficits in prepulse inhibition, a measure of sensorimotor gating. This finding adds to the knowledge about the neurophysiology of these neural substrates and circuitry involved with neuropsychiatric disorders.

Acknowledgments

The authors wish to thank Anni S. Lee for assistance with stereotaxic surgery and Stephanie Dulawa for invaluable help establishing the PPI paradigm in our laboratory. This work was supported by NIH grants T32MH-14185 (LBR), K08MH081190 (CP), R01MH091861 (CP), a NARSAD Young Investigator Award (CP), and the State of Connecticut through its support of the Abraham Ribicoff Research Facilities at the Connecticut Mental Health Center.

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