Quinolinic acid lesions of the ventral striatum reduce sensorimotor gating of acoustic startle in rats.
The startle reflex is inhibited when the startling stimulus is preceded 30-500 ms by a weak noise or 'prepulse'. While the primary startle circuit is organized at or below the pons, the amount of 'prepulse inhibition' (PPI) is modulated by forebrain activity and is reduced in certain neuropsychiatric disorders. The reduction of PPI in these disorders is thought to reflect disturbances in sensorimotor inhibition which underlie an inability to 'gate' irrelevant sensory, motor or cognitive information. PPI is altered by pharmacologic manipulations of the ventral striatum, which is thought to modulate PPI via sequential efferent projections through the ventral pallidum and pontine reticular formation. In the present study, we assessed the effects of cellular lesions of the ventral striatum (VS) on PPI. Quinolinic acid lesions of the VS significantly reduced PPI and increased startle amplitude; however, changes in PPI and startle amplitude were not significantly correlated within rats. Infusion of the GABA agonist muscimol into ventral striatal terminal fields in the ventral pallidum significantly restored PPI in VS-lesioned rats, but did not reverse lesion effects on startle amplitude. It was verified that muscimol infusions were made into an area which receives direct VS innervation, using ventral pallidal injections of the retrograde tracer Nuclear yellow in VS sham-lesioned rats. Cells in the ventral striatum appear to modulate sensorimotor gating of the startle reflex via a GABAergic innervation of the ventral pallidum.
Department of Neuroscience, UCSD School of Medicine, La Jolla 92093-0804.
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MH
Kodsi
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Swerdlow
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D007839:Functional Laterality; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D011149:Pons / Q000502:physiology*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D009118:Muscimol; D017378:Quinolinic Acid