Phase-specific pooling of sparse assembly activity by respiration-related brain oscillations

Abstract

Nasal breathing affects cognitive functions, but it has remained largely unclear how respiration-driven inputs shape information processing in neuronal circuits. Current theories emphasize the role of neuronal assemblies, coalitions of transiently active pyramidal cells, as the core unit of cortical network computations. Here, we show that respiration-related oscillations (RROs) directly pace the activation of neuronal assemblies in the medial prefrontal cortex (mPFC) of mice. Neuronal assemblies are more efficiently entrained than single neurons and activate preferentially during the descending phase of RROs. At the same time, overlap between individual assemblies is minimized during descending RRO due to the efficient recruitment of GABAergic neurons by assemblies. Our results thus suggest the RROs support cortical operations by defining time windows of enhanced yet segregated assembly activity.

Respiration-Driven Brain Oscillations in Emotional Cognition

“…Interestingly, optogenetic manipulation of fear-related assemblies in a 4 Hz phase-specific manner could bi-directionally modulate the amount of freezing, suggesting a causal role of assembly activity nested in respiration-driven prefrontal oscillations (Dejean et al, 2016 ). More recently, recordings from head-fixed mice presented evidence that the modulation of assembly patterns by RR might generalize to behavioral states other than fear ( Figure 5 C; Folschweiller and Sauer, 2021 ). In the absence of fearful stimuli, prefrontal assembly patterns are preferentially activated during the descending phase of respiration-driven oscillations.…”

“…The olfactory tubercle (OT) receives direct projections from the OB and the nucleus accumbens (NAcc) has been shown to be strongly entrained by RR (Karalis and Sirota, 2018). In the prefrontal cortex, the RR power increases from dorsal to ventral (Karalis and Sirota, 2018;Folschweiller and Sauer, 2021). Adapted from Voorn et al (2004); copyright ( 2004 (Figure 1A; Ito et al, 2014), and respiration has been argued to be an important synchronization signal for sensorimotor integration (for review see Kleinfeld et al, 2014).…”

“…While the origin and local nature of cortical RR LFP oscillations are thus well-validated, two key questions remain open: First, it is not entirely clear how the large-amplitude respiration-synchronous LFP is generated in the hippocampus and neocortex, or in other words how rhythmically oscillating discharges in axons from olfactory regions are translated into rhythmically active local populations (“translation problem”). A series of findings emphasize a central role of GABAergic interneurons in the generation of local RR: Single-unit recordings showed that a high proportion of GABAergic cells is phase-entrained by RR oscillations, and/or directly by rhythmic breathing, while the proportion of significantly coupled pyramidal cells is lower (Biskamp et al, 2017 ; Karalis and Sirota, 2018 ; Kőszeghy et al, 2018 ; Folschweiller and Sauer, 2021 ). Furthermore, subthreshold membrane oscillations in pyramidal cells of the parietal cortex seem to reflect inhibitory inputs, as they increase in amplitude when the holding potential is moved away from the reversal potential of GABAergic currents (Jung et al, 2019 ).…”

“…Left: Peak power for each mouse at 4 Hz at the most superficial recording site (light blue) and the deepest recording site (dark blue) of the mPFC. Reprinted from Folschweiller and Sauer ( 2021 ) under CC BY 4.0. * p < 0.05.…”

“…(C) Top: Neuronal assemblies activate during the descending part of the prefrontal respiration-related oscillation (RRO). Reprinted from Folschweiller and Sauer ( 2021 ) under CC BY 4.0. Bottom: RR creates time windows for assembly activation and might thus orchestrate the joint activity of distributed assembly members or facilitate assembly stabilization by offline reactivation (Dejean et al, 2016 ; Folschweiller and Sauer, 2021 ).…”