Catecholaminergic Modulation of Sensory Processing in functionally distinct Primary Sensory and Association Cortex

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Dokumentart: PhDThesis
Date: 2017
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biologie
Advisor: Logothetis, Nikos K. (Prof. Dr.)
Day of Oral Examination: 2017-05-03
DDC Classifikation: 000 - Computer science, information and general works
500 - Natural sciences and mathematics
570 - Life sciences; biology
Keywords: Dopamin , Noradrenalin , Nervenstimulation , Modulation , Präfrontaler Cortex
Other Keywords: Locus Coeruleus
Ventrales Tegmentales Areal
primärer somatosensorischer Kortex
prefrontal cortex
primary somatosensory cortex
prepulse inhibition
ventral tegmental area
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The vertebrate sensory system is enabled to differentiate between a vast variety of sensory information under different behavioral and environmental conditions. The required flexibility is provided by complex brain functions including neuromodulation. Specific structures contributing in neuromodulation of sensory processing are the noradrenergic nucleus locus coeruleus and the dopaminergic ventral tegmental area (VTA), combined referred to as catecholaminergic system. However, how catecholaminergic neuromodulation affects sensory processing in functionally different brain regions is not well discovered. To approach this question, experiments in anesthetized rats were conducted in order to examine qualitative differences of noradrenergic modulation of sensory processing between the functionally distinct primary somatosensory cortex (S1) and the associative medial prefrontal cortex (mPFC). These experiments confirmed the already reported function of noradrenaline (NE) in activation of the cortical state and increase of the signal-to-noise ratio (SNR) of sensory-evoked responses, however only for S1. In mPFC, reorganization of neuronal activity, orchestrated by NE, is suggested in order to adequately evaluate the biological relevance of the stimulus and integrate sensory and non-sensory information. Further results show that NE improves noxious somatosensory processing within the VTA to induce the observed reorganization of local networks in mPFC in synergy with dopamine (DA). A possible outcome includes enhanced sensory gating by suppression of irrelevant and accentuation of relevant network information. This prefrontal cortical function was finally specifically explored in awake rats. Target specific manipulation of DA release revealed that prefrontal DA is essential to ensure adequate prefronto-accumbal interactions which, in turn, are necessary for sensory gating. Together, this work demonstrated that catecholamines are needed to improve sensory processing in functionally distinct cortical and subcortical brain regions. Thereby, classical improvement of SNR is not the only mechanism but also the catecholaminergic modulation of complex local network dynamics contributes to processing of relevant or irrelevant sensory information.

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