Assessing the role of arousal state in sensorimotor gating and memory consolidation

Abstract

The brain state is a recurring, temporally enduring constellation of neural activity. It varies with or without external stimuli to both spatial and temporal extent. Brain state can be characterized in various dimensions, such as arousal, affective, cognitive, exploratory, and many others. Among them, the arousal state is the most well‐studied one. Neural activities that support sensory processing, motor control, decision making, mnemonic function are all influenced by the ongoing arousal level. However, the modulation of arousal state on different aspects of brain functions and behavioral outputs remains largely unexplored. In my Ph.D. work, I investigated the sensorimotor gating and memory consolidation across different arousal states, measured by the frontal electroencephalogram (EEG) and concurrently recorded animals' movements. Acoustic startle response (ASR) and prepulse inhibition (PPI) were used to assess the sensorimotor function (Manuscript 1). To manipulate the arousal level, we delivered electrical micro‐stimulation pulses to the locus coeruleus (LC), the nucleus that sends brain‐wide projections and regulates arousal via releasing noradrenaline (NA) in the target brain regions. We observed that the magnitude of the startle response was significantly reduced by increasing cortical arousal effectively with phasic LC activation.

Next, by examining startle response across spontaneous fluctuations of arousal levels, we found that the smallest startle response during the active awake state, further suggesting that arousal states modulated ASR amplitudes. To study memory consolidation, we selected a well‐studied hippocampal neural event, sharp wave‐ripple (SPW‐R), which is essential for various memory functions. We characterized neuronal activity in the LC (Manuscript 2) and mediodorsal thalamus (MD, Manuscript 3) through multi‐site electrophysiological recordings around SPW‐Rs during quiet awake state and slow wave sleep. Overall, we observed suppressions of both LC and MD spiking activity around SPW‐Rs. The

SPW‐R‐associated suppression in both structures differed across arousal states, being strongest and the most consistent during awake ripples. Taken together, these results showed that the fluctuation of the arousal state could modulate neural activity and behavioral output, including both the basic motor reflex and higher cognitive function, in this case, memory consolidation. The engagement of neural circuits and cross‐regional communications in the same behavioral context highly depends on the ongoing background brain activity.