Cognitive, Behavioral, and Systems NeuroscienceResearch PaperLesions of the dorsomedial striatum disrupt prepulse inhibition
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.
References (52)
- et al.
Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results
Biol Psychiatry
(1996) - et al.
Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder
Biol Psychiatry
(2005) - et al.
Ventral pallidal GABA-A receptors regulate prepulse inhibition of acoustic startle
Brain Res
(1995) - et al.
Mitochondrial toxin 3-nitropropionic acid produces startle reflex abnormalities and striatal damage in rats that model some features of Huntington's disease
Neurosci Lett
(1997) - et al.
Reduced prepulse inhibition after electrolytic lesions of nucleus accumbens subregions in the rat
Brain Res
(1997) - et al.
Regulation of prepulse inhibition by ventral pallidal projections
Brain Res Bull
(1997) - et al.
Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited
Neurosci Biobehav Rev
(2008) - et al.
Separate neuronal populations of the rat globus pallidus projecting to the subthalamic nucleus, auditory cortex and pedunculopontine tegmental area
Neuroscience
(1992) - et al.
Human basal ganglia volume asymmetries on magnetic resonance images
Magn Reson Imaging
(1993) - et al.
DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the ventral pallidum
Brain Res
(1997)