Lesions of the dorsomedial striatum disrupt prepulse inhibition

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.

FIGURE 1. Effect of dorsomedial striatal lesions on PPI

A. Excitotoxic dorsomedial striatal lesions were made by stereotaxic infusion of NMDA in mice, as described in the text. Lesion extent was documented by immunohistochemistry for GFAP; regions of gliosis were manually outlined. Superimposed regions of lesion for all mice used in this experiment are shown. B. Lesioned mice showed impaired PPI at all frequency relative to controls. See text for statistical comparisons. C. Lesions had no effect on startle on Pulse-Alone trials over the course of the four blocks of trials. PPI data are drawn from Blocks 2 and 3. See text for statistics.

FIGURE 2. Effect of central dorsal striatal lesions on PPI

A. Lesions were produced and documented as in Figure 1. Region of lesion for all mice used in this experiment are shown; three mice were excluded due to an absence of clear bilateral lesions in the target region. B. These lesions had no effect on PPI at any prepulse intensity. See text for statistical comparisons. C. Similarly, these lesions had no effect on absolute startle magnitude across the course of the four blocks of the experiment.