Respiratory entrainment of units in the mouse parietal cortex depends on vigilance state.

Synchronous oscillations are essential for coordinated activity in neuronal networks and, hence, for behavior and cognition. While most network oscillations are generated within the central nervous system, recent evidence shows that rhythmic body processes strongly influence activity patterns throughout the brain. A major factor is respiration (Resp), which entrains multiple brain regions at the mesoscopic (local field potential) and single-cell levels. However, it is largely unknown how such Resp-driven rhythms interact or compete with internal brain oscillations, especially those with similar frequency domains. In mice, Resp and theta (θ) oscillations have overlapping frequencies and co-occur in various brain regions. Here, we investigated the effects of Resp and θ on neuronal discharges in the mouse parietal cortex during four behavioral states which either show prominent θ (REM sleep and active waking (AW)) or lack significant θ (NREM sleep and waking immobility (WI)). We report a pronounced state-dependence of spike modulation by both rhythms. During REM sleep, θ effects on unit discharges dominate, while during AW, Resp has a larger influence, despite the concomitant presence of θ oscillations. In most states, unit modulation by θ or Resp increases with mean firing rate. The preferred timing of Resp-entrained discharges (inspiration versus expiration) varies between states, indicating state-specific and different underlying mechanisms. Our findings show that neurons in an associative cortex area are differentially and state-dependently modulated by two fundamentally different processes: brain-endogenous θ oscillations and rhythmic somatic feedback signals from Resp.

Breathing modulates gamma synchronization across species.

Nasal respiration influences brain dynamics by phase-entraining neural oscillations at the same frequency as the breathing rate and by phase-modulating the activity of faster gamma rhythms. Despite being widely reported, we still do not understand the functional roles of respiration-entrained oscillations. A common hypothesis is that these rhythms aid long-range communication and provide a privileged window for synchronization. Here we tested this hypothesis by analyzing electrocorticographic (ECoG) recordings in mice, rats, and cats during the different sleep-wake states. We found that the respiration phase modulates the amplitude of cortical gamma oscillations in the three species, although the modulated gamma frequency bands differed with faster oscillations (90-130 Hz) in mice, intermediate frequencies (60-100 Hz) in rats, and slower activity (30-60 Hz) in cats. In addition, our results also show that respiration modulates olfactory bulb-frontal cortex synchronization in the gamma range, in which each breathing cycle evokes (following a delay) a transient time window of increased gamma synchrony. Long-range gamma synchrony modulation occurs during quiet and active wake states but decreases during sleep. Thus, our results suggest that respiration-entrained brain rhythms orchestrate communication in awake mammals.

Respiration and rapid eye movement (REM) sleep substructure: short versus long episodes.

Rapid eye movement (REM) sleep in rodents is defined by the presence of theta rhythm in the absence of movement. The amplitude and frequency of theta oscillations have been used to distinguish between tonic and phasic REM sleep. However, tonic REM sleep has not been further subdivided, although characteristics of network oscillations such as cross-frequency coupling between theta and gamma vary within this sub-state. Recently, it has been shown that theta-gamma coupling depends on an optimal breathing rate of ~5 Hz. The frequency of breathing varies strongly throughout REM sleep, and the duration of single REM sleep episodes ranges from several seconds to minutes, whereby short episodes predominate. Here we studied the relation between breathing frequency, accelerometer activity, and the length of REM sleep periods. We found that small movements detected with three-dimensional accelerometry positively correlate with breathing rate. Interestingly, breathing is slow in short REM sleep episodes, while faster respiration regimes exclusively occur after a certain delay in longer REM sleep episodes. Thus, merging REM sleep episodes of different lengths will result in a predominance of slow respiration due to the higher occurrence of short REM sleep periods. Moreover, our results reveal that not only do phasic REM sleep epochs predominantly occur during long REM sleep episodes, but that the long episodes also have faster theta and higher gamma activity. These observations suggest that REM sleep can be further divided from a physiological point of view depending on its duration. Higher levels of arousal during REM sleep, indicated by higher breathing rates, can only be captured in long REM sleep episodes.

Temporal Relations between Cortical Network Oscillations and Breathing Frequency during REM Sleep.

Nasal breathing generates a rhythmic signal which entrains cortical network oscillations in widespread brain regions on a cycle-to-cycle time scale. It is unknown, however, how respiration and neuronal network activity interact on a larger time scale: are breathing frequency and typical neuronal oscillation patterns correlated? Is there any directionality or temporal relationship? To address these questions, we recorded field potentials from the posterior parietal cortex of mice together with respiration during REM sleep. In this state, the parietal cortex exhibits prominent θ and γ oscillations while behavioral activity is minimal, reducing confounding signals. We found that the instantaneous breathing frequency strongly correlates with the instantaneous frequency and amplitude of both θ and γ oscillations. Cross-correlograms and Granger causality revealed specific directionalities for different rhythms: changes in θ activity precede and Granger-cause changes in breathing frequency, suggesting control by the functional state of the brain. On the other hand, the instantaneous breathing frequency Granger causes changes in γ frequency, suggesting that γ is influenced by a peripheral reafference signal. These findings show that changes in breathing frequency temporally relate to changes in different patterns of rhythmic brain activity. We hypothesize that such temporal relations are mediated by a common central drive likely to be located in the brainstem.

Differential modulation of parietal cortex activity by respiration and θ oscillations.

The simultaneous, local integration of information from widespread brain regions is an essential feature of cortical computation and particularly relevant for multimodal association areas such as the posterior parietal cortex. Slow, rhythmic fluctuations in the local field potentials (LFPs) are assumed to constitute a global signal aiding interregional communication through the long-range synchronization of neuronal activity. Recent work demonstrated the brain-wide presence of a novel class of slow neuronal oscillations that are entrained by nasal respiration. However, whether there are differences in the influence of the respiration-entrained rhythm (RR) and the endogenous theta (θ) rhythm over local networks is unknown. In this work, we aimed at characterizing the impact of both classes of oscillations on neuronal activity in the posterior parietal cortex of mice. We focused our investigations on a θ-dominated state (rapid eye movement sleep) and an RR-dominated state (wake immobility). Using linear silicon probes implanted along the dorsoventral cortical axis, we found that the LFP-depth distributions of both rhythms show differences in amplitude and coherence but no phase shift. Using tetrode recordings, we demonstrate that a substantial fraction of parietal neurons is modulated by either RR or θ or even by both rhythms simultaneously. Interestingly, the phase and cortical depth dependence of spike-field coupling differ for these oscillations. We further show through intracellular recordings in urethane-anesthetized mice that synaptic inhibition is likely to play a role in generating respiration-entrainment at the membrane potential level. We conclude that θ and respiration differentially affect neuronal activity in the parietal cortex.NEW & NOTEWORTHY Nasal respiration generates a rhythmic signal that entrains large portions of the mammalian brain into respiration-coupled field potentials. Here, we report the simultaneous presence of respiratory rhythm (RR) and θ oscillations in the parietal association cortex of mice. Despite their overlapping frequencies, both rhythms differ in their state-dependent power and differentially entrain the discharge behavior of units. We conclude that network activity in the parietal cortex is synchronized by two different physiological oscillation patterns.

Hippocampal-prefrontal interactions during spatial decision-making.

The hippocampus has been linked to memory encoding and spatial navigation, while the prefrontal cortex is associated with cognitive functions such as decision-making. These regions are hypothesized to communicate in tasks that demand both spatial navigation and decision-making processes. However, the electrophysiological signatures underlying this communication remain to be better elucidated. To investigate the dynamics of the hippocampal-prefrontal interactions, we have analyzed their local field potentials and spiking activity recorded from rats performing a spatial alternation task on a figure eight-shaped maze. We found that the phase coherence of theta peaked around the choice point area of the maze. Moreover, Granger causality revealed a hippocampus → prefrontal cortex directionality of information flow at theta frequency, peaking at starting areas of the maze, and on the reverse direction at delta frequency, peaking near the turn onset. Additionally, the patterns of phase-amplitude cross-frequency coupling within and between the regions also showed spatial selectivity, and hippocampal theta and prefrontal delta modulated not only gamma amplitude but also inter-regional gamma synchrony. Finally, we found that the theta rhythm dynamically modulated neurons in both regions, with the highest modulation at the choice area; interestingly, prefrontal cortex neurons were more strongly modulated by the hippocampal theta rhythm than by their local field rhythm. In all, our results reveal maximum electrophysiological interactions between the hippocampus and the prefrontal cortex near the decision-making period of the spatial alternation task, corroborating the hypothesis that a dynamic interplay between these regions takes place during spatial decisions.

Selective entrainment of gamma subbands by different slow network oscillations.

Theta oscillations (4-12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30-160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown. Here, we investigated two different patterns of oscillatory network activity, theta and respiration-induced network rhythms, in four brain regions of freely moving mice: olfactory bulb (OB), prelimbic cortex (PLC), parietal cortex (PAC), and dorsal hippocampus [cornu ammonis 1 (CA1)]. We report differential state- and region-specific coupling between the slow large-scale rhythms and superimposed fast oscillations. During awake immobility, all four regions displayed a respiration-entrained rhythm (RR) with decreasing power from OB to CA1, which coupled exclusively to the 80- to 120-Hz gamma subband (γ2). During exploration, when theta activity was prevailing, OB and PLC still showed exclusive coupling of RR with γ2 and no theta-gamma coupling, whereas PAC and CA1 switched to selective coupling of theta with 40- to 80-Hz (γ1) and 120- to 160-Hz (γ3) gamma subbands. Our data illustrate a strong, specific interaction between neuronal activity patterns and respiration. Moreover, our results suggest that the coupling between slow and fast oscillations is a general brain mechanism not limited to the theta rhythm.

Place and Grid Cells in a Loop: Implications for Memory Function and Spatial Coding.

Place cells in the hippocampus and grid cells in the medial entorhinal cortex have different codes for space. However, how one code relates to the other is ill understood. Based on the anatomy of the entorhinal-hippocampal circuitry, we constructed a model of place and grid cells organized in a loop to investigate their mutual influence in the establishment of their codes for space. Using computer simulations, we first replicated experiments in rats that measured place and grid cell activity in different environments, and then assessed which features of the model account for different phenomena observed in neurophysiological data, such as pattern completion and pattern separation, global and rate remapping of place cells, and realignment of grid cells. We found that (1) the interaction between grid and place cells converges quickly; (2) the spatial code of place cells does not require, but is altered by, grid cell input; (3) plasticity in sensory inputs to place cells is key for pattern completion but not pattern separation; (4) grid realignment can be explained in terms of place cell remapping as opposed to the other way around; (5) the switch between global and rate remapping is self-organized; and (6) grid cell input to place cells helps stabilize their code under noisy and/or inconsistent sensory input. We conclude that the hippocampus-entorhinal circuit uses the mutual interaction of place and grid cells to encode the surrounding environment and propose a theory on how such interdependence underlies the formation and use of the cognitive map.SIGNIFICANCE STATEMENT The mammalian brain implements a positional system with two key pieces: place and grid cells. To gain insight into the dynamics of place and grid cell interaction, we built a computational model with the two cell types organized in a loop. The proposed model accounts for differences in how place and grid cells represent different environments and provides a new interpretation in which place and grid cells mutually interact to form a coupled code for space.

Olfactory bulb drives respiration-coupled beta oscillations in the rat hippocampus.

The synchronization of neuronal oscillations has been suggested as a mechanism to coordinate information flow between distant brain regions. In particular, the olfactory bulb (OB) and the hippocampus (HPC) have been shown to exhibit oscillations in the beta frequency range (10-20 Hz) that are likely to support communication between these structures. Here, we further characterize features of beta oscillations in OB and HPC of rats anesthetized with urethane. We find that beta oscillations simultaneously appear in HPC and OB and phase-lock across structures. Moreover, Granger causality analysis reveals that OB beta activity drives HPC beta. The laminar voltage profile of beta in HPC shows the maximum amplitude in the dentate gyrus (DG), spatially coinciding with olfactory inputs to this region. Finally, we also find that the respiratory cycle and respiration-coupled field potential rhythms (1-2 Hz)-but not theta oscillations (3-5 Hz)-modulate beta amplitude in OB and HPC. In all, our results support the hypothesis that beta activity mediates the communication between olfactory and hippocampal circuits in the rodent brain.

A Respiration-Coupled Rhythm in the Rat Hippocampus Independent of Theta and Slow Oscillations.

UNLABELLED: During slow-wave sleep and deep anesthesia, the rat hippocampus displays a slow oscillation (SO) that follows "up-and-down" state transitions in the neocortex. There has been recent debate as to whether this local field potential (LFP) rhythm reflects internal processing or entrains with respiratory inputs. To solve this issue, here we have concomitantly recorded respiration along with hippocampal, neocortical, and olfactory bulb (OB) LFPs in rats anesthetized with urethane. During the course of anesthesia, LFPs transitioned between activity states characterized by the emergence of different oscillations. By jointly analyzing multisite LFPs and respiratory cycles, we could distinguish three types of low-frequency hippocampal oscillations: (1) SO, which coupled to neocortical up-and-down transitions; (2) theta, which phase-reversed across hippocampal layers and was largest at the fissure; and (3) a low-frequency rhythm with largest amplitude in the dentate gyrus, which coupled to respiration-entrained oscillations in OB and to respiration itself. In contrast, neither theta nor SO coupled to respiration. The hippocampal respiration-coupled rhythm and SO had frequency <1.5 Hz, whereas theta tended to be faster (>3 Hz). Tracheotomy abolished hippocampal respiration-coupled rhythm, which was restored by rhythmic delivery of air puffs into the nasal cavity. These results solve the apparent contradictions among previous studies by demonstrating that the rat hippocampus produces multiple types of low-frequency oscillations. Because they synchronize with different brain circuits, however, we postulate that each activity pattern plays a unique role in information processing. SIGNIFICANCE STATEMENT: The rat hippocampus exhibits a large-amplitude slow oscillation (<1.5 Hz) during deep sleep and anesthesia. It is currently debated whether this rhythm reflects internal processing with the neocortex or entrainment by external inputs from rhythmic nasal respiration, which has similar frequency. Here we reconcile previous studies by showing that the hippocampus can actually produce two low-frequency rhythms at nearby frequencies: one that indeed couples to respiration and another that is coupled to the neocortex. We further show that the respiration-coupled rhythm differs from theta oscillations. The results support a role for brain oscillations in connecting distant brain regions, and posit the respiratory cycle as an important reference for neuronal communication between olfactory and memory networks.

Hippocampal Respiration-Driven Rhythm Distinct from Theta Oscillations in Awake Mice.

We have recently described a slow oscillation in the hippocampus of urethane-anesthetized mice, which couples to nasal respiration and is clearly distinct from co-occurring theta oscillations. Here we set out to investigate whether such type of patterned network activity, which we named "hippocampal respiration rhythm" (HRR), also occurs in awake mice. In freely moving mice, instantaneous respiration rate is extremely variable, and respiration is superimposed by bouts of sniffing. To reduce this variability, we clamped the behavior of the animal to either awake immobility or treadmill running by using a head-fixed setup while simultaneously recording respiration and field potentials from the olfactory bulb (OB) and hippocampus. Head-fixed animals often exhibited long periods of steady respiration rate during either immobility or running, which allowed for spectral and coherence analyses with a sufficient frequency resolution to sort apart respiration and theta activities. We could thus demonstrate the existence of HRR in awake animals, namely, a respiration-entrained slow rhythm with highest amplitude at the dentate gyrus. HRR was most prominent during immobility and running with respiration rates slower than theta oscillations. Nevertheless, HRR could also be faster than theta. Discharges of juxtacellularly recorded cells in CA1 and dentate gyrus were modulated by HRR and theta oscillations. Granger directionality analysis revealed that HRR is caused by the OB and that theta oscillations in OB are caused by the hippocampus. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks. SIGNIFICANCE STATEMENT: Olfaction is a major sense in rodents. In consequence, the olfactory bulb (OB) should be able to transmit information to downstream regions. Here we report potential mechanisms underlying such information transfer. We demonstrate the existence of a respiration-entrained rhythm in the hippocampus of awake mice. Frequencies of the hippocampal respiration rhythm (HRR) overlap with classical theta oscillations, but both rhythms are clearly distinct. HRR is most prominent in the dentate gyrus, especially when respiration is slower than theta frequency. Discharges of neurons in CA1 and dentate gyrus are modulated by both HRR and theta. Directionality analysis shows that HRR is caused by the OB. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks.

Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.

S100B protein and neuron-specific enolase as predictors of cognitive dysfunction after coronary artery bypass graft surgery: A prospective observational study.

BACKGROUND: Postoperative cognitive dysfunction (POCD) may be related to the systemic inflammatory response and an increase in serum markers of brain injury such as S100B protein and neuron-specific enolase (NSE). OBJECTIVE: The study aims to evaluate the association between POCD and serum levels of S100B and NSE after coronary artery bypass grafting surgery (CABG). DESIGN: Prospective observational study. SETTING: Single university teaching hospital. PATIENTS: We investigated 88 patients undergoing CABG. MAIN OUTCOMES MEASURES: Cognitive function was measured preoperatively, and at the 21st and 180th postoperative days (i.e. 6 months after surgery). S100B protein and NSE serum levels were evaluated preoperatively, after induction of anaesthesia, at the end of surgery and at 6 and 24 h after surgery. RESULTS: The incidence of POCD was 26.1% at 21 days after surgery and 22.7% at 6 months after surgery. Increased serum levels of S100B protein and NSE were observed postoperatively and may indicate brain damage. CONCLUSION: Although serum levels of S100B protein and NSE are both significantly increased postoperatively, our findings indicate that serum levels of S100B protein may be more accurate than NSE in the detection of POCD after CABG. TRIAL REGISTRATION: NCT01550159.

Slow oscillations in the mouse hippocampus entrained by nasal respiration.

Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominent θ oscillations at frequencies between 4 and 12 Hz, which are superimposed by phase-coupled γ oscillations (30-100 Hz). These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation. Here we report a new type of oscillation at near-θ frequencies (2-4 Hz) in the hippocampus of urethane-anesthetized mice. The rhythm is highly coherent with nasal respiration and with rhythmic field potentials in the olfactory bulb: hence, we called it hippocampal respiration-induced oscillations. Despite the similarity in frequency range, several features distinguish this pattern from locally generated θ oscillations: hippocampal respiration-induced oscillations have a unique laminar amplitude profile, are resistant to atropine, couple differently to γ oscillations, and are abolished when nasal airflow is bypassed by tracheotomy. Hippocampal neurons are entrained by both the respiration-induced rhythm and concurrent θ oscillations, suggesting a direct interaction between endogenous activity in the hippocampus and nasal respiratory inputs. Our results demonstrate that nasal respiration strongly modulates hippocampal network activity in mice, providing a long-range synchronizing signal between olfactory and hippocampal networks.

Local field potentials in the gustatory cortex carry taste information.

It has been recently shown that local field potentials (LFPs) from the auditory and visual cortices carry information about sensory stimuli, but whether this is a universal property of sensory cortices remains to be determined. Moreover, little is known about the temporal dynamics of sensory information contained in LFPs following stimulus onset. Here we investigated the time course of the amount of stimulus information in LFPs and spikes from the gustatory cortex of awake rats subjected to tastants and water delivery on the tongue. We found that the phase and amplitude of multiple LFP frequencies carry information about stimuli, which have specific time courses after stimulus delivery. The information carried by LFP phase and amplitude was independent within frequency bands, since the joint information exhibited neither synergy nor redundancy. Tastant information in LFPs was also independent and had a different time course from the information carried by spikes. These findings support the hypothesis that the brain uses different frequency channels to dynamically code for multiple features of a stimulus.

On high-frequency field oscillations (>100 Hz) and the spectral leakage of spiking activity.

Recent reports converge to the idea that high-frequency oscillations in local field potentials (LFPs) represent multiunit activity. In particular, the amplitude of LFP activity above 100 Hz-commonly referred to as "high-gamma" or "epsilon" band-was found to correlate with firing rate. However, other studies suggest the existence of true LFP oscillations at this frequency range that are different from the well established ripple oscillations. Using multisite recordings of the hippocampus of freely moving rats, we show here that high-frequency LFP oscillations can represent either the spectral leakage of spiking activity or a genuine rhythm, depending on recording location. Both spike-leaked, spurious activity and true fast oscillations couple to theta phase; however, the two phenomena can be clearly distinguished by other key features, such as preferred coupling phase and spectral signatures. Our results argue against the idea that all high-frequency LFP activity stems from spike contamination and suggest avoiding defining brain rhythms solely based on frequency range.

Increase in hippocampal theta oscillations during spatial decision making.

The processing of spatial and mnemonic information is believed to depend on hippocampal theta oscillations (5-12 Hz). However, in rats both the power and the frequency of the theta rhythm are modulated by locomotor activity, which is a major confounding factor when estimating its cognitive correlates. Previous studies have suggested that hippocampal theta oscillations support decision-making processes. In this study, we investigated to what extent spatial decision making modulates hippocampal theta oscillations when controlling for variations in locomotion speed. We recorded local field potentials from the CA1 region of rats while animals had to choose one arm to enter for reward (goal) in a four-arm radial maze. We observed prominent theta oscillations during the decision-making period of the task, which occurred in the center of the maze before animals deliberately ran through an arm toward goal location. In speed-controlled analyses, theta power and frequency were higher during the decision period when compared to either an intertrial delay period (also at the maze center), or to the period of running toward goal location. In addition, theta activity was higher during decision periods preceding correct choices than during decision periods preceding incorrect choices. Altogether, our data support a cognitive function for the hippocampal theta rhythm in spatial decision making.

Beta2 oscillations (23-30 Hz) in the mouse hippocampus during novel object recognition.

The oscillatory activity of hippocampal neuronal networks is believed to play a role in memory acquisition and consolidation. Particular focus has been given to characterising theta (4-12 Hz), gamma (40-100 Hz) and ripple (150-250 Hz) oscillations. Beyond these well-described network states, few studies have investigated hippocampal beta2 (23-30 Hz) activity in vivo and its link to behaviour. A previous sudy showed that the exploration of novel environments may lead to the appearance of beta2 oscillations in the mouse hippocampus. In the present study we characterised hippocampal beta2 oscillations in mice during an object recognition task. We found prominent bursts of beta2 oscillations in the beginning of novel exploration sessions (four new objects), which could be readily observed by spectral analysis and visual inspection of local field potentials. Beta2 modulated hippocampal but not neocortical neurons and its power decreased along the session. We also found increased beta2 power in the beginning of a second exploration session performed 24 h later in a slightly modified environment (two new, two familiar objects), but to a lesser extent than in the first session. However, the increase in beta2 power in the second exploration session became similar to the first session when we pharmacologically impaired object recognition in a new set of experiments performed 1 week later. Our results suggest that hippocampal beta2 activity is associated with a dynamic network state tuned for novelty detection and which may allow new learning to occur.

Waveform-based classification of dentate spikes.

Synchronous excitatory discharges from the entorhinal cortex (EC) to the dentate gyrus (DG) generate fast and prominent patterns in the hilar local field potential (LFP), called dentate spikes (DSs). As sharp-wave ripples in CA1, DSs are more likely to occur in quiet behavioral states, when memory consolidation is thought to take place. However, their functions in mnemonic processes are yet to be elucidated. The classification of DSs into types 1 or 2 is determined by their origin in the lateral or medial EC, as revealed by current source density (CSD) analysis, which requires recordings from linear probes with multiple electrodes spanning the DG layers. To allow the investigation of the functional role of each DS type in recordings obtained from single electrodes and tetrodes, which are abundant in the field, we developed an unsupervised method using Gaussian mixture models to classify such events based on their waveforms. Our classification approach achieved high accuracies (> 80%) when validated in 8 mice with DG laminar profiles. The average CSDs, waveforms, rates, and widths of the DS types obtained through our method closely resembled those derived from the CSD-based classification. As an example of application, we used the technique to analyze single-electrode LFPs from apolipoprotein (apo) E3 and apoE4 knock-in mice. We observed that the latter group, which is a model for Alzheimer's disease, exhibited wider DSs of both types from a young age, with a larger effect size for DS type 2, likely reflecting early pathophysiological alterations in the EC-DG network, such as hyperactivity. In addition to the applicability of the method in expanding the study of DS types, our results show that their waveforms carry information about their origins, suggesting different underlying network dynamics and roles in memory processing.

5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats.

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.