Subcortical influence on the respiratory coordination of cortical neurodynamics related to cognition

Slow cortical oscillations, such as theta (5-9Hz) band activity, may provide 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. The role of theta/GBO coupling (TG coupling) in cognitive processing is well established. However, more recent studies have observed that nasal respiration can also temporally coordinate dynamic neural activity in the brain, reflected as respiratory-entrained oscillations (REO), which 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 attention-related performance. Aim 1: RG coupling in the frontoparietal attentional network correlates with performance in an attention-demanding operant task. We will measure respiration and REO in local field potentials in select brain regions to evaluate RG coupling during an operant signal detection task used to measure sustained 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 BF parvalbumin neurons (BF-PV) will impair/improve attention-related performance in the rPVT. Our preliminary findings show that closed-loop gamma frequency stimulation (CLS) of BF-PV in relation to respiratory inhalation, but not exhalation, promotes RG coupling. Therefore, we will utilize this CLS paradigm to determine how modulation of RG coupling impacts attention-related performance. Across a range of select neuropsychiatric illnesses, the pathological processes behind cognitive deficits involve abnormal neural temporal dynamics. Thus, these studies will help to inform the development of translational therapies to restore/enhance cognitive function.