Pupil Fluctuations Track Fast Switching of Cortical States during Quiet Wakefulness

Abstract

Neural responses are modulated by brain state, which varies with arousal, attention, and behavior. In mice, running and whisking desynchronize the cortex and enhance sensory responses, but the quiescent periods between bouts of exploratory behaviors have not been well-studied. We found that these periods of “quiet wakefulness” were characterized by state fluctuations on a timescale of 1–2 seconds. Small fluctuations in pupil diameter tracked these state transitions in multiple cortical areas. During dilation, the intracellular membrane potential was desynchronized, sensory responses were enhanced, and population activity was less correlated. In contrast, constriction was characterized by increased low-frequency oscillations and higher ensemble correlations. Specific subtypes of cortical interneurons were differentially activated during dilation and constriction, consistent with their participation in the observed state changes. Pupillometry has been used to index attention and mental effort in humans, but the intracellular dynamics and differences in population activity underlying this phenomenon were previously unknown.

VIP+ interneurons control neocortical activity across brain states

“…These mice allow for GCaMP Ca 2ϩ signals to be measured both from VIPϩ cells (td-Tomatoϩ) and non-VIP (td-TomatoϪ; putative pyramidal cells) cell populations. VIPϩ cells were previously shown to be specifically active during locomotion (Fu et al 2014;Reimer et al 2014). We also observed this locomotion-VIPϩ cell coupling (Fig.…”

“…VIPϩ cells are active not only during locomotion (Fu et al 2014;Reimer et al 2014) but also during awake immobility, under light anesthesia, or in response to visual stimulation. Moreover, VIPϩ cell activity dynamics closely couple with the activity dynamics of the network, and suppression of VIPϩ cells shifts the network to a low-activity regime.…”

Temporal correlations among functionally specialized striatal neural ensembles in reward-conditioned mice

“…Numerous studies suggest that correlated spontaneous neural activity reflects the underlying connectivity of the network (Ko et al 2011;Ringach 2009;Stern et al 1998). As such, the resting state has become an important measurement modality in neuroscience (Cole et al 2014;Raichle 2010;Reimer et al 2014). To focus on spontaneous activity we calculated pairwise spike count Pearson correlations of units recorded in the same session during intermittent periods when animals were at rest.…”

Astrocytes regulate cortical state switching in vivo

“…Although the slow oscillation is cortically generated (11)(12)(13)(14), the circuit mechanisms that drive the cortex into the slow-wave state remain unclear. Because neuronal responses to external stimuli are modulated by brain state, the mechanisms that drive transitions to different states-the relatively synchronized, slow-oscillation-dominated state or the desynchronized, more "awake" or attentive state-have recently been of intense interest, although most of these have focused on the shift to the desynchronized state (15)(16)(17)(18)(19). These studies have critically examined the effects of neuronal and sensory manipulations on brain state and the effects of brain state on processing, but have not investigated how other cellular circuit components may influence these states.…”