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Abstract:
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The present research reports the first comprehensive map of brain networks underlying latent inhibition learning , the first application of structural equation modeling to cytochrome oxidase data , and the first effects of methylene blue , a known metabolic enhancer , on latent inhibition . In latent inhibition , repeated exposure to a stimulus results in a latent form of learning that inhibits subsequent associations with that stimulus . As neuronal energy demand to form learned associations changes , so does the induction of the respiratory enzyme cytochrome oxidase . Therefore , cytochrome oxidase can be used as an endpoint metabolic marker of the effects of experience on regional brain metabolic capacity . Quantitative cytochrome oxidase histochemistry was used to map brain regions in mice trained on a tone -footshock fear conditioning paradigm with either tone preexposure (latent inhibition ) , conditioning only (acquisition ) , conditioning followed by tone alone (extinction ) , or no handling or conditioning (naïve ) . In normal latent inhibition , the ventral cochlear nucleus , medial geniculate , CA1 hippocampus , and perirhinal cortex showed modified metabolic capacity due to latent inhibition . Structural equation modeling was used to determine the causal influences in an anatomical network of these regions and others thought to mediate latent inhibition , including the accumbens and entorhinal cortex . An uncoupling of ascending influences between auditory regions was observed in latent inhibition . There was also a reduced influence on the accumbens from the perirhinal cortex in both latent inhibition and extinction . These results suggest a specific network with a neural mechanism of latent inhibition that involves sensory gating , as evidenced by modifications in metabolic capacity , effective connectivity between auditory regions , and reduced hippocampal influence on the accumbens . The effects of methylene blue on disrupted latent inhibition were also investigated . Reduced tone -alone presentations disrupted the latent inhibition effect and led to an increase in freezing behavior . Repeated low -dose administration of methylene blue decreased freezing levels and facilitated the disrupted latent inhibition effect . Methylene blue administration also resulted in changes in metabolic capacity in limbic and cortical regions . A unique functional neural network was found in methylene blue -restored latent inhibition that emphasized sensory gating of auditory information , attention processing , and cortical inhibition of behavior . |