Date of Award
Master of Science
Focusing attention depends on filtering irrelevant sensory stimuli to prevent brain overload. This ability of our brain to block or “gate” such information is a pre-attentive neuronal mechanism known as sensorimotor gating (SG). SG abnormalities have been linked to a variety of psychiatric disorders, including schizophrenia. Initial studies related to the SG circuitry were performed more than four decades ago (Graham, 1975). However, SG is still the subject of numerous current studies involving both humans and animal models. Despite these research efforts, knowledge gaps persist regarding the identity neurons involved, their locations in different brain regions and their precise functional roles in SG. Here, our objective was to further identify and functionally characterize the neural structures and brain circuits that contribute to SG. The caudal pontine reticular nucleus (PnC) is a central structure within the SG circuitry (Davis et al., 1982, Koch et al., 1993; Fendt and Koch, 1999). We hypothesized that direct connections originating from various brain regions exist and innervate the PnC, yet remain to be identified. Such key experiments are crucial to later determine whether such brain regions exert an alternate gating mechanism by acting directly onto the PnC.
To test our hypoThesis, we first used a retrograde neuronal tracer to identify brain regions anatomically connected to the PnC. Retrogradely labeled cells were found in the medial prefrontal cortex (mPFC). Therefore next, we used an in vitro Optogenetics approach combined to extracellular field electrophysiological recordings in brain slices by injecting Channelrhodopsin-2 (ChR-2) into the mouse mPFC. This was done to further confirm that this brain region (ie., the mPFC) is synaptically connected to the PnC. Photostimulation of ChR2-expressing mPFC fibers in acute PnC slices produced synaptic responses confirming the integrity of the connection. Our preliminary data suggest for the first time that excitatory afferent fibers originating from the mPFC project onto PnC neurons. Future work will determine if this functional connection contributes to or modulates sensorimotor gating.
Received from ProQuest
Sebastian Andres Pace
Pace, Sebastian Andres, "Characterization Of A Medial Prefrontal Cortex - Caudal Pontine Reticular Nucleus Relevant To Sensorimotor Gating" (2016). Open Access Theses & Dissertations. 715.