University thesis:
Dissertation, Universität Freiburg, 2018
Footnote:
Description:
Abstract: In everyday life altering environmental conditions require flexible adaptation of planned or already initiated actions. Humans and animals are forced to constantly update their behavior to avoid maladaptive actions. Studies linked responseinhibition deficits to several neurological diseases and emphasized the critical role of the PFC for appropriately timed actions (Aron, 2011; Aron et al., 2014a; Chambers et al., 2009). These neuropsychiatric disorders include fronto-temporal dementia (Pompanin et al., 2014), and Parkinson’s disease (Gauggel et al., 2004).<br>In the present thesis we investigated two mechanisms of motor inhibition: reactive and proactive stopping. We combined optogenetic and electrophysiological techniques to analyze the functional role of five key subareas of the rat medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) in a response-preparation task (Eagle and Baunez, 2010; Wallis, 2011; Uylings et al., 2003). We observed two main effects following optogenetic inhibition of mPFC and OFC subareas: (1) inactivation of mPFC induced drastic changes during proactive behavior, and (2) OFC inhibition significantly impaired the rats’ reactive motor control. Specifically, while prelimbic cortex (PL) inhibition induced an increase of premature responses, infralimbic cortex (IL) inactivation resulted in a decreased number of early lever releases. In contrast, optogenetic inhibition of OFC subareas (mainly the ventral orbitofrontal cortex (VO)) significantly impaired the rats’ ability to respond rapidly after external cues. Additionally, we designed and optimized optrodes for combined optogenetics and electrophysiology in behaving rats. We compared a selection of commercially available as well as custom-made optrodes which are appropriate to target specific PFC subareas. These devices were implanted and subsequently used for electrophysiological recordings in task performing rats implemented. Consistent with our optogenetic experiments, task modulated PL units showed significantly reduced activity before early releases, while the opposite was true for the average of all recorded IL neurons. Further, principal component alanysis (PCA) of VO activity revealed strong components around the tone and reaction time (RT) window of correct trials, which supports the role of this lateral OFC subregion during the reactive phase of the task. Our data argue for opposing roles of IL and PL in directing proactive behavior and argue for an involvement of OFC in predominantly reactive motor control. By attributing defined roles to rodent PFC sections, this study represents a good starting point for future experiments (Jäckel, 2017; Herold, 2018) investigating further descending targets of the complex neural network involved in inhibitory processes