Subcortical influence on the respiratory coordination of cortical neurodynamicsrelated to cognition

缓慢的皮层振荡，如θ波段活动（5-9Hz），可能对大脑活动的一致性至关重要

Slow cortical oscillations, such as theta band activity (5-9Hz), may be critical for coherence of activity over large distances, providing a mechanism for interregional communication involved in neural processing. Faster gamma band oscillations (GBO; 30-200 Hz) are thought to play a major role in higher-level cognitive processing including attention. While the role of Theta/GBO coupling in select aspects of cognitive processing has been a topic of intense interest, recent findings suggest that nasal respiration can also temporally coordinate dynamic neural activity in the brain. These respiratory-entrained oscillations also exhibit high phase- amplitude coupling to GBO (RG coupling) during select behaviors. Presently it is unknown if RG coupling has a role in cognition. Our overarching hypothesis posits that the strength of RG coupling in the attention- related frontoparietal network (prelimbic and posterior parietal cortices) will correlate with vigilant attention- dependent performance. Aim 1: RG coupling in the frontoparietal attentional network correlates with performance in an attention-demanding operant task. We will measure respiration and respiratory-entrained oscillations in local field potentials in select brain regions to evaluate RG coupling during an operant signal detection task used to measure vigilant attention, the rodent psychomotor vigilance task (rPVT). In the rPVT, mice maintain attention to a stimulus location, and respond to detection of a brief and unpredictable cue with a short-latency operant response to receive food reward. Prior to correct trials, we predict that RG coupling will be strong in the frontoparietal attention network, and that fast reaction times will correlate with robust RG coupling. In contrast, prior to omission trials (attention failures), we predict that RG coupling will be diminished. Aim 2: Attenuation/promotion of RG coupling by means of optogenetic manipulation of basal forebrain parvalbumin neurons will impair/improve performance in the rPVT. Our preliminary findings show that closed-loop gamma frequency stimulation of basal forebrain parvalbumin neurons in relation to respiratory inhalation, but not exhalation, promotes RG coupling. Therefore, we will utilize this stimulation paradigm to determine how modulation of RG coupling impacts performance in the rPVT. Across a range of select neuropsychiatric illnesses, the pathological processes behind cognitive deficits involve abnormal neural temporal dynamics. Thus, these basic research studies will help to inform the development of translational therapies to restore/enhance cognitive function.