Home » Central noradrenergic circuits regulating prepulse inhibition of the startle response. by Karen Marie Alsene
Central noradrenergic circuits regulating prepulse inhibition of the startle response. Karen Marie Alsene

Central noradrenergic circuits regulating prepulse inhibition of the startle response.

Karen Marie Alsene

Published
ISBN : 9781109273083
NOOKstudy eTextbook
321 pages
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 About the Book 

Prepulse inhibition (PPI) refers to the normal attenuation of the startle response when a weak prestimulus precedes the startling stimulus. PPI is an index of sensorimotor gating, or the ability to filter information from the internal and externalMorePrepulse inhibition (PPI) refers to the normal attenuation of the startle response when a weak prestimulus precedes the startling stimulus. PPI is an index of sensorimotor gating, or the ability to filter information from the internal and external environments, and is deficient in patients with certain psychiatric disorders, such as schizophrenia. Despite the large number of studies on the neurotransmitter and neuroanatomical substrates of PPI, relatively little is known about the role of the norepinephrine (NE) system in regulating sensorimotor gating. This is surprising, given the prominent role of NE in processes relevant to attention and cognitive functioning. Thus, the experiments in the present thesis were designed to systematically examine the role of NE in regulating PPI by exploring the neural circuitry through which NE modulates PPI. First, we found that stimulation of alpha1 NE receptors in the brain disrupts PPI, indicating that NE could be disrupting PPI through stimulation of central alpha1 receptors. Second, pharmacological stimulation of the locus coeruleus (LC), the primary source of NE to the forebrain, disrupts PPI, presumably through putative release of NE in LC terminal regions. Importantly, LC stimulation-induced deficits in PPI were blocked by atypical antipsychotics, but not by the traditional antipsychotics, indicating that the LC-NE system might be an important circuit in the efficacy of atypical antipsychotic treatment. Third, stimulation of alpha1 or beta NE receptors in the posterior region of the medial prefrontal cortex or the nucleus accumbens shell (terminal regions of the LC) disrupts PPI, indicating these might be regions through which NE from the LC is disrupting PPI. Fourth, blockade of alpha1 NE receptors prevents deficits in PPI induced by amphetamine administration, indicating that alpha1 receptors are necessary for this psychotomimetic drug to disrupt PPI. Taken together, these results overwhelmingly indicate that increasing central NE transmission disrupts PPI. Importantly, these studies constitute the first attempt to characterize the neural substrates underlying NE regulation of PPI, which is an important area of research because it furthers our understanding of NE regulation of cognition and also has potential clinical and therapeutic applications.