Adriano Bretanha Lopes Tort

Summary: Neuronal activity synchronous to breathing is salient across the mammalian brain. These modulations are typically characterized as oscillating signals phase-locked to the ongoing breathing rhythm and treated as evidence for respiratory ‘entrainment’ of cortical and subcortical oscillations. Since activation of the olfactory circuitry has been identified as their preponderant source, we wondered whether respiratory brain signals could be better understood as sequences of evoked sensory potentials. To help distinguish between these scenarios, we set out to quantify the detailed alignment of prefrontal cortex local field potentials (LFPs) to the nasal airflow cycle across the natural repertoire of rat breathing. We found that, while LFP and breathing show salient synchrony for all breathing modes, the phase of their locking is a strict linear function of respiratory rate. We explain this by showing that LFPs align to nasal airflow with a constant time lag of 100 ms, irrespective of breathing rate. Segmenting by breathing cycles revealed that LFP peaks and fast-gamma bursts are time-locked to inhalations, while LFP troughs and slow-gamma activity time-lock to exhalations. Our results support the view that respiratory signals across the frontal brain of rodents are sensory potentials evoked by cyclic ortho- and retronasal airflow.

Sharp-wave ripples (SWRs) are hippocampal network oscillations associated with memory consolidation. They are characterized by the co-occurrence of fast and slow field potentials across CA1 layers: the fast-frequency oscillations, known as ripples, are prominent in the pyramidal cell layer, where they coincide with increased neuronal spiking, while slower negative transients, referred to as sharp waves, occur simultaneously in the stratum radiatum . SWRs have traditionally been considered globally synchronous across the hippocampus; however, recent evidence suggests that ripples may be less synchronous than previously thought, particularly between the two hemispheres (Villalobos et al., 2017). In this study, we revisited this question using a unique dataset from probes spanning the septo-temporal axis of CA1 in rats. Our results demonstrate that ripples are phase-locked within but not between hemispheres, although their occurrence remains time-locked across both the septo-temporal axis and hemispheres. We also observed a similar synchronicity pattern for spiking activity: neurons are locally phase-coupled and globally time-coupled to ripple events. Interneurons exhibit a much stronger phase coupling to both ipsilateral and contralateral ripples than pyramidal neurons. These findings suggest that ripples are locally phase-coupled through pyramidal–interneuron interactions, with global time-locking likely driven by a common bilateral CA3 input and potentially modulated by interneuron circuits.

Sharp-wave ripples (SWRs) are hippocampal network oscillations associated with memory consolidation. They are characterized by the co-occurrence of fast and slow field potentials across CA1 layers: the fast-frequency oscillations, known as ripples, are prominent in the pyramidal cell layer, where they coincide with increased neuronal spiking, while slower negative transients, referred to as sharp waves, occur simultaneously in the stratum radiatum. SWRs have traditionally been considered globally synchronous across the hippocampus; however, recent evidence suggests that ripples may be less synchronous than previously thought, particularly between the two hemispheres (Villalobos et al., 2017). In this study, we revisited this question using a unique dataset from probes spanning the septotemporal axis of CA1. Our results demonstrate that ripples are phase-locked within but not between hemispheres, although their occurrence remains time-locked across both the septo-temporal axis and hemispheres. We also observed a similar synchronicity pattern for spiking activity: neurons are locally phase-coupled and globally time-coupled to ripple events. Interneurons exhibit a much stronger phase coupling to both ipsilateral and contralateral ripples than pyramidal neurons. These findings suggest that ripples are locally phase-coupled through pyramidal-interneuron interactions, with global time-locking likely driven by a common bilateral CA3 input and potentially modulated by interneuron circuits.

The striatum plays a central role in motor control, yet how it dynamically represents variables such as locomotion speed, particularly across varying behavioral contexts, remains incompletely understood. Here, we investigated striatal encoding of locomotion speed in rats performing an automated T-maze task. We found that the activity of most (78%) analyzed striatal neurons— referred to as speed cells—was robustly correlated, either positively or negatively, with locomotion speed. This population included both putative medium spiny neurons (MSNs; 74%) and fast-spiking interneurons (FSIs; 82%). Speed-related activity was remarkably stable, showing no significant influence of elapsed time, cue type, spatial choice, or trial outcome. Additionally, positively correlated MSNs tended to precede speed changes, while positively correlated FSI activity typically followed, as did negatively correlated neurons for both types. This suggests distinct roles for different striatal cells in movement modulation. Speed cells exhibited strong modulation at movement onset and offset, yet also maintained correlations with speed throughout locomotion bouts. Finally, the firing rates of speed cells reliably predicted locomotion speed, outperforming non-speed cells and chance levels; decoding accuracy further improved when data from multiple neurons were combined, consistent with a population code. Together, these results demonstrate a robust, context-independent representation of locomotion speed in the rat striatum, driven by diverse cell types, and extends previous findings to a task with greater cognitive demands.

Hippocampal theta (6–12 Hz) oscillations coordinate neural activity during spatial navigation and are strongly related to locomotion speed. However, recent research has yielded conflicting evidence on whether theta rhythms are primarily modulated by acceleration or instantaneous speed. Moreover, the role of movement transitions—at locomotion onset and offset—has often been overlooked, despite potentially involving distinct dynamics not explained by speed or acceleration alone. Previous studies have rarely controlled for locomotion timing and speed, limiting our ability to dissociate the contributions of speed, acceleration, and movement transitions. To address this, we used a computer-controlled treadmill to induce rat locomotion under three distinct conditions: (a) movement transitions, (b) steady running at constant speed, and (c) locomotion with continuous acceleration. This setup allowed precise spectral analysis of hippocampal theta oscillations across conditions. We found that treadmill-triggered movement transitions produced sustained increases in theta power and transient increases in theta frequency. Upon treadmill stop, theta power decreased slowly, whereas theta frequency dropped rapidly. Steady running elevated both theta power and frequency relative to rest. During constant-speed trials, both metrics increased with speed and remained stable over time. Notably, the acceleration rate itself had no effect on theta power or frequency. Instead, during accelerating trials, theta frequency increased progressively with instantaneous speed, underscoring speed as the primary modulator. In summary, our results show that movement transitions induce distinct, sustained changes in theta power and transient changes in theta frequency, while instantaneous speed—not acceleration—governs hippocampal theta frequency. Significance statement: The precise contributions of movement transitions, speed, and acceleration to hippocampal theta oscillations remain unclear due to confounding factors in freely moving paradigms. To resolve this, we employed a computer-controlled treadmill to systematically isolate each locomotor variable under tightly controlled conditions. Our results demonstrate that movement transitions induce distinct changes in theta power and frequency, and that instantaneous speed—not acceleration—robustly modulates theta frequency across hippocampal subregions. These findings clarify an ongoing debate and refine our understanding of how specific locomotor dynamics shape hippocampal activity during navigation.

Neuronal activities that synchronize with the breathing rhythm have been found in humans and a host of mammalian species, not only in brain areas closely related to respiratory control or olfactory coding but also in areas linked to emotional and higher cognitive functions. In parallel, evidence is mounting for modulations of perception and action by the breathing cycle. In this Review, we discuss the extent to which brain activity locks to breathing across areas, levels of organization and brain states, and the physiological origins of this global synchrony. We describe how waves of sensory activity evoked by nasal airflow spread through brain circuits, synchronizing neuronal populations to the breathing cycle and modulating faster oscillations, cell assembly formation and cross-area communication, thereby providing a mechanistic link from breathing to neural coding, emotion and cognition. We argue that, through evolution, the breathing rhythm has come to shape network functions across species.

Sharp-wave ripples (SWRs) are hippocampal network oscillations associated with memory consolidation. They are characterized by the co-occurrence of fast and slow field potentials across CA1 layers: the fast-frequency oscillations, known as ripples, are prominent in the pyramidal cell layer, where they coincide with increased neuronal spiking, while slower negative transients, referred to as sharp waves, occur simultaneously in the stratum radiatum . SWRs have traditionally been considered globally synchronous across the hippocampus; however, recent evidence suggests that ripples may be less synchronous than previously thought, particularly between the two hemispheres (Villalobos et al., 2017). In this study, we revisited this question using a unique dataset from probes spanning the septotemporal axis of CA1. Our results demonstrate that ripples are phase-locked within but not between hemispheres, although their occurrence remains time-locked across both the septo-temporal axis and hemispheres. We also observed a similar synchronicity pattern for spiking activity: neurons are locally phase-coupled and globally time-coupled to ripple events. Interneurons exhibit a much stronger phase coupling to both ipsilateral and contralateral ripples than pyramidal neurons. These findings suggest that ripples are locally phase-coupled through pyramidal-interneuron interactions, with global time-locking likely driven by a common bilateral CA3 input and potentially modulated by interneuron circuits.

Anxiety elicits various physiological responses, including changes in the respiratory rate and neuronal activity within specific brain regions such as the medial prefrontal cortex (mPFC). Previous research suggests that the olfactory bulb (OB) modulates the mPFC through respiration-coupled oscillations (RCOs), which have been linked to fear-related freezing behavior. Nevertheless, the impact of breathing on frontal brain networks during other negative emotional responses, such as anxiety-related states characterized by higher breathing rates, remains unclear. To address this, we subjected rats to the elevated plus maze (EPM) paradigm while simultaneously recording respiration and local field potentials in the OB and mPFC. Our findings demonstrate distinct respiratory patterns during EPM exploration: slower breathing frequencies prevailed in the closed arms, whereas faster frequencies were observed in the open arms, independent of locomotor activity, indicating that anxiety-like states are associated with increased respiratory rates. Additionally, we identified RCOs at different frequencies, mirroring the bimodal distribution of respiratory frequencies. RCOs exhibited higher power during open-arm exploration, when they showed greater coherence with breathing at faster frequencies. Furthermore, we confirmed that nasal respiration drives RCOs in frontal brain regions and found a stronger effect during faster breathing. Interestingly, we observed that the frequency of prefrontal gamma oscillations modulated by respiration increased with breathing frequency. Overall, our study provides evidence for a significant influence of breathing on prefrontal cortex networks during anxious states, shedding light on the complex interplay between respiratory physiology and emotional processing.