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Fetal valproate syndrome and sensory processing by the superior colliculus

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Dendrinos, Georgia
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2010
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dissertation
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Sensory processing disorder (SPD) is characterized by an inability to filter sensory information, particularly simultaneously arriving multimodal inputs. We examined the effects of prenatal exposure to valproic acid (VPA), an SPD-linked teratogen, on the behavior of juvenile and adult rats, and on physiology and the prenatal and postnatal of the superior colliculus, a critical multisensory integration center in the brain. VPA exposed rats showed dose-dependent deficits in colliculus-dependent behaviors including startle response, prepulse inhibition and nociceptive thresholds. Some deficits reversed with age. In extracellular recordings from anesthetized rats, collicular neurons of control and VPA-treated rats showed no difference in spontaneous firing rates or evoked responses to presentations of unimodal stimuli. However, neurons from VPA-treated rats responded with significantly higher magnitudes to concurrent stimulus presentations of different modalities. Individual neurons from control and VPA-treated rats responded less to a multimodal stimulus than a unimodal stimulus. This response depression was exhibited differentially for control and VPA-treated rats depending on stimulus intensity. At low intensity combinations of multimodal stimuli, more neurons of VPA-treated rats showed a significant change in response to multimodal stimuli than unimodal stimuli. At high intensity combinations, neurons responded significantly differently to multimodal stimuli than unimodal stimuli, regardless of treatment. Stereological analyses revealed that the embryonic brain of animals exposed to VPA in utero were significantly smaller with volumetric decreases in several structures including the cortex, thalamus, and superior colliculus. Postnatally, colliculi of VPA-treated rats had significantly fewer parvalbumin-positive neurons, a subset of GABAergic cells. These results suggest that prenatal VPA treatment affects the development of the superior colliculus and leads to persistent anatomical and physiological changes which are evidenced by aberrant behavior in tasks that require sensory processing.

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University of Maryland in Baltimore. Neuroscience. Ph.D. 2010
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