Local Field Potential Oscillations Research Articles

Primacy of vision shapes behavioral strategies and neural substrates of spatial navigation in marmoset hippocampus

The role of the hippocampus in spatial navigation has been primarily studied in nocturnal mammals, such as rats, that lack many adaptations for daylight vision. Here we demonstrate that during 3D navigation, the common marmoset, a new world primate adapted to daylight, predominantly uses rapid head-gaze shifts for visual exploration while remaining stationary. During active locomotion marmosets stabilize the head, in contrast to rats that use low-velocity head movements to scan the environment as they locomote. Pyramidal neurons in the marmoset hippocampus CA3/CA1 regions predominantly show mixed selectivity for 3D spatial view, head direction, and place. Exclusive place selectivity is scarce. Inhibitory interneurons are predominantly mixed selective for angular head velocity and translation speed. Finally, we found theta phase resetting of local field potential oscillations triggered by head-gaze shifts. Our findings indicate that marmosets adapted to their daylight ecological niche by modifying exploration/navigation strategies and their corresponding hippocampal specializations.

Subthalamic nucleus synchronization between beta band local field potential and single-unit activity in Parkinson's disease.

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings. Magnitude of STA-LFP was greater within the STN compared to extra-STN structures along the trajectory path, despite no difference in percentage of the total power. Within the STN, there was a higher percent beta power in dorsal compared to ventral STN but no difference in STA-LFP magnitude. Further refining the comparison to high versus low beta peak power recordings inside the STN to evaluate if single-unit activity synchronized more strongly with beta band activity in areas of high beta power resulted in a significantly higher STA magnitude for areas of high beta power. Overall, these results suggest that STN single units strongly synchronize to beta activity, particularly units in areas ofhigh beta power.

Auditory Competition and Coding of Relative Stimulus Strength across Midbrain Space Maps of Barn Owls.

The natural environment challenges the brain to prioritize the processing of salient stimuli. The barn owl, a sound localization specialist, exhibits a circuit called the midbrain stimulus selection network, dedicated to representing locations of the most salient stimulus in circumstances of concurrent stimuli. Previous competition studies using unimodal (visual) and bimodal (visual and auditory) stimuli have shown that relative strength is encoded in spike response rates. However, open questions remain concerning auditory-auditory competition on coding. To this end, we present diverse auditory competitors (concurrent flat noise and amplitude-modulated noise) and record neural responses of awake barn owls of both sexes in subsequent midbrain space maps, the external nucleus of the inferior colliculus (ICx) and optic tectum (OT). While both ICx and OT exhibit a topographic map of auditory space, OT also integrates visual input and is part of the global-inhibitory midbrain stimulus selection network. Through comparative investigation of these regions, we show that while increasing strength of a competitor sound decreases spike response rates of spatially distant neurons in both regions, relative strength determines spike train synchrony of nearby units only in the OT. Furthermore, changes in synchrony by sound competition in the OT are correlated to gamma range oscillations of local field potentials associated with input from the midbrain stimulus selection network. The results of this investigation suggest that modulations in spiking synchrony between units by gamma oscillations are an emergent coding scheme representing relative strength of concurrent stimuli, which may have relevant implications for downstream readout.

Perturbing cortical networks: in vivo electrophysiological consequences of pan-neuronal chemogenetic manipulations using deschloroclozapine.

Chemogenetic techniques, specifically the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), have become invaluable tools in neuroscience research. Yet, the understanding of how Gq- and Gicoupled DREADDs alter local field potential (LFP) oscillations in vivo remains incomplete. This study investigates the in vivo electrophysiological effects of DREADD actuation by deschloroclozapine, on spontaneous firing rate and LFP oscillations recorded from the anterior cingulate cortex in lightly anesthetized male rats. Unexpectedly, in response to the administration of deschloroclozapine, we observed inhibitory effects with pan-neuronal hM3D(Gq) stimulation, and excitatory effects with pan-neuronal hM4D(Gi) stimulation in a significant portion of neurons. These results emphasize the need to account for indirect perturbation effects at the local neuronal network level in vivo, particularly when not all neurons express the chemogenetic receptors uniformly. In the current study, for instance, the majority of cells that were transduced with both hM3D(Gq) and hM4D(Gi) were GABAergic. Moreover, we found that panneuronal cortical chemogenetic modulation can profoundly alter oscillatory neuronal activity, presenting a potential research tool or therapeutic strategy in several neuropsychiatric models and diseases. These findings help to optimize the use of chemogenetic techniques in neuroscience research and open new possibilities for novel therapeutic strategies.

Acetylcholine Engages Distinct Amygdala Microcircuits to Gate Internal Theta Rhythm.

Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.

Cell-type-specific representation of spatial context in the rat prefrontal cortex

The ability to represent one's own position in relation to cues, goals, or threats is crucial to successful goal-directed behavior. Using optotagging in knock-in rats expressing Cre recombinase in parvalbumin (PV) neurons (PV-Cre rats), we demonstrate cell-type-specific encoding of spatial and movement variables in the medial prefrontal cortex (mPFC) during goal-directed reward seeking. Single neurons encoded the conjunction of the animal's spatial position and the run direction, referred to as the spatial context. The spatial context was most prominently represented by the inhibitory PV interneurons. Movement toward the reward was signified by increased local field potential (LFP) oscillations in the gamma band but this LFP signature was not related to the spatial information in the neuronal firing. The results highlight how spatial information is incorporated into cognitive operations in the mPFC. The presented PV-Cre line opens the door for expanded research approaches in rats.

Physiological effects of dual target DBS in an individual with Parkinson's disease and a sensing-enabled pulse generator

IntroductionDeep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus (GP) is an established therapy for Parkinson's disease (PD). Novel DBS devices can record local field potential (LFP) physiomarkers from the STN or GP. While beta (13–30 Hz) and gamma (40–90 Hz) STN and GP LFP oscillations correlate with PD motor severity and with therapeutic effects of treatments, STN-GP interactions in electrophysiology in patients with PD are not well characterized. MethodsSimultaneous bilateral STN and GP LFPs were recorded in a patient with PD who received bilateral STN-DBS and GP-DBS. Power spectra in each target and STN-GP coherence were assessed in various ON- and OFF-levodopa and DBS states, both at rest and with voluntary movement. ResultsOFF-levodopa and OFF-DBS, beta peaks were present at bilateral STN and GP, coincident with prominent STN-GP beta coherence. Levodopa and dual-target-DBS (simultaneous STN-DBS and GP-DBS) completely suppressed STN-GP coherence. Finely-tuned gamma (FTG) activity at half the stimulation frequency (62.5 Hz) was seen in the STN during GP-DBS at rest. To assess the effects of movement on FTG activity, we recorded LFPs during instructed movement. We observed FTG activity in bilateral GP and bilateral STN during contralateral body movements while on GP-DBS and ON-levodopa. No FTG was seen with STN-DBS or dual-target-DBS. ConclusionDual-target-DBS and levodopa suppressed STN-GP coherence. FTG throughout the basal ganglia was induced by GP-DBS in the presence of levodopa and movement. This bilateral STN-FTG and GP-FTG corresponded with the least severe bradykinesia state, suggesting a pro-kinetic role for FTG.

Effect of the closed-loop hippocampal low-frequency stimulation on seizure severity, learning, and memory in pilocarpine epilepsy rat model.

In this study, the anticonvulsant action of closed-loop, low-frequency deep brain stimulation (DBS) was investigated. In addition, the changes in brain rhythms and functional connectivity of the hippocampus and prefrontal cortex were evaluated. Epilepsy was induced by pilocarpine in male Wistar rats. After the chronic phase, a tripolar electrode was implanted in the right ventral hippocampus and a monopolar electrode in medial prefrontal cortex (mPFC). Subjects' spontaneous seizure behaviors were observed in continuous video recording, while the local field potentials (LFPs) were recorded simultaneously. In addition, spatial memory was evaluated by the Barnes maze test. Applying hippocampal DBS, immediately after seizure detection in epileptic animals, reduced their seizure severity and duration, and improved their performance in Barnes maze test. DBS reduced the increment in power of delta, theta, and gamma waves in pre-ictal, ictal, and post-ictal periods. Meanwhile, DBS increased the post-ictal-to-pre-ictal ratio of theta band. DBS decreased delta and increased theta coherences, and also increased the post-ictal-to-pre-ictal ratio of coherence. In addition, DBS increased the hippocampal-mPFC coupling in pre-ictal period and decreased the coupling in the ictal and post-ictal periods. Applying closed-loop, low-frequency DBS at seizure onset reduced seizure severity and improved memory. In addition, the changes in power, coherence, and coupling of the LFP oscillations in the hippocampus and mPFC demonstrate low-frequency DBS efficacy as an antiepileptic treatment, returning LFPs to a seemingly non-seizure state in subjects that received DBS.

Brain-wide human oscillatory local field potential activity during visual working memory

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

High-Frequency Local Field Potential Oscillations for Pigeons in Effective Turning

Flexible turning behavior endows Homing Pigeons (Columba livia domestica) with high adaptability and intelligence in long-distance flight, foraging, hazard avoidance, and social interactions. The present study recorded the activity pattern of their local field potential (LFP) oscillations and explored the relationship between different bands of oscillations and turning behaviors in the formatio reticularis medialis mesencephali (FRM). The results showed that the C (13–60 Hz) and D (61–130 Hz) bands derived from FRM nuclei oscillated significantly in active turning, while the D and E (131–200 Hz) bands oscillated significantly in passive turning. Additionally, compared with lower-frequency stimulation (40 Hz and 60 Hz), 80 Hz stimulation can effectively activate the turning function of FRM nuclei. Electrical stimulation elicited stronger oscillations of neural activity, which strengthened the pigeons’ turning locomotion willingness, showing an enhanced neural activation effect. These findings suggest that different band oscillations play different roles in the turning behavior; in particular, higher-frequency oscillations (D and E bands) enhance the turning behavior. These findings will help us decode the complex relationship between bird brains and behaviors and are expected to facilitate the development of neuromodulation techniques for animal robotics.

Anxiety control by astrocytes in the lateral habenula

The potential role of astrocytes in lateral habenula (LHb) in modulating anxiety was explored in this study. The habenula are a pair of small nuclei located above the thalamus, known for their involvement in punishment avoidance and anxiety. Herein, we observed an increase in theta-band oscillations of local field potentials (LFPs) in the LHb when mice were exposed to anxiety-inducing environments. Electrical stimulation of LHb at theta-band frequency promoted anxiety-like behavior. Calcium (Ca2+) levels and pH in the cytosol of astrocytes and local brain blood volume changes were studied in mice expressing either a Ca2+ or a pH sensor protein specifically in astrocytes and mScarlet fluorescent protein in the blood plasma using fiber photometry. An acidification response to anxiety was observed. Photoactivation of archaerhopsin-T (ArchT), an optogenetic tool that acts as an outward proton pump, results in intracellular alkalinization. Photostimulation of LHb in astrocyte-specific ArchT-expressing mice resulted in dissipation of theta-band LFP oscillation in an anxiogenic environment and suppression of anxiety-like behavior. These findings provide evidence that LHb astrocytes modulate anxiety and may offer a new target for treatment of anxiety disorders.

Enhancement of low gamma oscillations by volitional conditioning of local field potential in the primary motor and visual cortex of mice.

Volitional control of local field potential oscillations in low gamma band via brain machine interface can not only uncover the relationship between low gamma oscillation and neural synchrony but also suggest a therapeutic potential to reverse abnormal local field potential oscillation in neurocognitive disorders. In nonhuman primates, the volitional control of low gamma oscillations has been demonstrated by brain machine interface techniques in the primary motor and visual cortex. However, it is not clear whether this holds in other brain regions and other species, for which gamma rhythms might involve in highly different neural processes. Here, we established a closed-loop brain-machine interface and succeeded in training mice to volitionally elevate low gamma power of local field potential in the primary motor and visual cortex. We found that the mice accomplished the task in a goal-directed manner and spiking activity exhibited phase-locking to the oscillation in local field potential in both areas. Moreover, long-term training made the power enhancement specific to direct and adjacent channel, and increased the transcriptional levels of NMDA receptors as well as that of hypoxia-inducible factor relevant to metabolism. Our results suggest that volitionally generated low gamma rhythms in different brain regions share similar mechanisms and pave the way for employing brain machine interface in therapy of neurocognitive disorders.

Subthalamic and pallidal neurons are modulated during externally cued movements in Parkinson's disease

External sensory cues can reduce freezing of gait in people with Parkinson's disease (PD), yet the role of the basal ganglia in these movements is unclear. We used microelectrode recordings to examine modulations in single unit (SU) and oscillatory local field potentials (LFP) during auditory-cued rhythmic pedaling movements of the feet. We tested five blocks of increasing cue frequencies (1 Hz, 1.5 Hz, 2 Hz, 2.5 Hz, and 3 Hz) in 24 people with PD undergoing deep brain stimulation surgery of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Single unit firing and beta band LFPs (13–30 Hz) in response to movement onsets or cue onsets were examined. We found that the timing accuracy of foot pedaling decreased with faster cue frequencies. Increasing cue frequencies also attenuated firing rates in both STN and GPi neurons. Peak beta power in the GPi and STN showed different responses to the task. GPi beta power showed persistent suppression with fast cues and phasic modulation with slow cues. STN beta power showed enhanced beta synchronization following movement. STN beta power also correlated with rate of pedaling. Overall, we showed task-related responses in the GPi and STN during auditory-cued movements with differential roles in sensory and motor control. The results suggest a role for both input and output basal ganglia nuclei in auditory rhythmic pacing of gait-like movements in PD.

Orchestration of saccadic eye-movements by brain rhythms in macaque Frontal Eye Field

Visual perception has been suggested to operate on temporal ‘chunks’ of sensory input, rather than on a continuous stream of visual information. Saccadic eye movements impose a natural rhythm on the sensory input, as periods of steady fixation between these rapid eye movements provide distinct temporal segments of information. Ideally, the timing of saccades should be precisely locked to the brain’s rhythms of information processing. Here, we investigated such locking of saccades to rhythmic neural activity in rhesus monkeys performing a visual foraging task. We found that saccades are phase-locked to local field potential oscillations (especially, 9–22 Hz) in the Frontal Eye Field, with the phase of oscillations predictive of the saccade onset as early as 100 ms prior to these movements. Our data also indicate a functional role of this phase-locking in determining the direction of saccades. These findings show a tight—and likely important—link between oscillatory brain activity and rhythmic behavior that imposes a rhythmic temporal structure on sensory input, such as saccadic eye movements.

Stimulus-Induced Theta-Band LFP Oscillations Format Neuronal Representations of Social Chemosignals in the Mouse Accessory Olfactory Bulb.

Social communication is crucial for the survival of many species. In most vertebrates, a dedicated chemosensory system, the vomeronasal system (VNS), evolved to process ethologically relevant chemosensory cues. The first central processing stage of the VNS is the accessory olfactory bulb (AOB), which sends information to downstream brain regions via AOB mitral cells (AMCs). Recent studies provided important insights about the functional properties of AMCs, but little is known about the principles that govern their coordinated activity. Here, we recorded local field potentials (LFPs) and single-unit activity in the AOB of adult male and female mice during presentation of natural stimuli. Our recordings reveal prominent LFP theta-band oscillatory episodes with a characteristic spatial pattern across the AOB. Throughout an experiment, the AOB network shows varying degrees of similarity to this pattern, in a manner that depends on the sensory stimulus. Analysis of LFP signal polarity and single-unit activity indicates that oscillatory episodes are generated locally within the AOB, likely representing a reciprocal interaction between AMCs and granule cells. Notably, spike times of many AMCs are constrained to the negative LFP oscillation phase in a manner that can drastically affect integration by downstream processing stages. Based on these observations, we propose that LFP oscillations may gate, bind, and organize outgoing signals from individual AOB neurons to downstream processing stages. Our findings suggest that, as in other neuronal systems and brain regions, population-level oscillations play a key role in organizing and enhancing transmission of socially relevant chemosensory information.SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is the first central stage of the vomeronasal system, a chemosensory system dedicated to processing cues from other organisms. Information from the AOB is conveyed to other brain regions via activity of its principal neurons, AOB mitral cells (AMCs). Here, we show that socially relevant sensory stimulation of the mouse vomeronasal system leads not only to changes in AMC activity, but also to distinct theta-band (∼5 Hz) oscillatory episodes in the local field potential. Notably AMCs favor the negative phase of these oscillatory events. Our findings suggest a novel mechanism for the temporal coordination of distributed patterns of neuronal activity, which can serve to efficiently activate downstream processing stages.

Frontal cortex activity during the production of diverse social communication calls in marmoset monkeys

Vocal communication is essential for social behaviors in humans and non-human primates. While the frontal cortex is crucial to human speech production, its role in vocal production in non-human primates has long been questioned. It is unclear whether activities in the frontal cortex represent diverse vocal signals used in non-human primate communication. Here we studied single neuron activities and local field potentials (LFP) in the frontal cortex of male marmoset monkeys while the animal engaged in vocal exchanges with conspecifics in a social environment. We found that both single neuron activities and LFP were modulated by the production of each of the four major call types. Moreover, neural activities showed distinct patterns for different call types and theta-band LFP oscillations showed phase-locking to the phrases of twitter calls, suggesting a neural representation of vocalization features. Our results suggest important functions of the marmoset frontal cortex in supporting the production of diverse vocalizations in communication.

Sensing with deep brain stimulation device in epilepsy: Aperiodic changes in thalamic local field potential during seizures.

Thalamic deep brain stimulation (DBS) is an effective therapeutic option in patients with drug-resistant epilepsy. Recent DBS devices with sensing capabilities enable chronic, outpatient local field potential (LFP) recordings. Whereas beta oscillations have been demonstrated to be a useful biomarker in movement disorders, the clinical utility of DBS sensing in epilepsy remains unclear. Our aim was to determine LFP features that distinguish ictal from inter-ictal states, which may aid in tracking seizure outcomes with DBS. Electrophysiology data were obtained from DBS devices implanted in the anterior nucleus (N = 12) or centromedian nucleus (N = 2) of the thalamus. Power spectra recorded during patient/caregiver-marked seizure events were analyzed with a method that quantitatively separates the oscillatory and non-oscillatory/aperiodic components of the LFP using non-parametric statistics, without the need for pre-specification of the frequency bands of interest. Features of the LFP parameterized using this algorithm were compared with those from inter-ictal power spectra recorded in clinic. Oscillatory activity in multiple canonical frequency bands was identified from the power spectra in 86.48% of patient-marked seizure events. Delta oscillations were present in all patients, followed by theta (N = 10) and beta (N = 9). Although there were no differences in oscillatory LFP features between the ictal and inter-ictal states, there was a steeper decline in the 1/f slope of the aperiodic component of the LFP during seizures. Our work highlights the potential and shortcomings of chronic LFP recordings in thalamic DBS for epilepsy. Findings suggest that no single frequency band in isolation clearly differentiates seizures, and that features of aperiodic LFP activity may be clinically-relevant biomarkers of seizures.

The decoupling between hemodynamic parameters and neural activity implies a complex origin of spontaneous brain oscillations.

Spontaneous low-frequency oscillations play a key role in brain activity. However, the underlying mechanism and origin of low-frequency oscillations remain under debate. Optical imaging and an electrophysiological recording system were combined to investigate spontaneous oscillations in the hemodynamic parameters and neuronal activity of awake and anesthetized mice after Nω-nitro-L-arginine methyl ester (L-NAME) administration. The spectrum of local field potential (LFP) signals was significantly changed by L-NAME, which was further corroborated by the increase in energy and spatial synchronization. The important finding was that L-NAME triggered regular oscillations in both LFP signals and hemodynamic signals. Notably, the frequency peak of hemodynamic signals can be different from that of LFP oscillations in awake mice. A model of the neurovascular system was proposed to interpret this mismatch of peak frequencies, supporting the view that spontaneous low-frequency oscillations arise from multiple sources.

The Dopaminergic System Modulates the Electrophysiological Activity of the Suprachiasmatic Nucleus Dependent on the Circadian Cycle.

The suprachiasmatic nucleus of the hypothalamus (SCN) controls mammalian circadian rhythms. Circadian rhythms influence the dopaminergic system, and dopaminergic tone impresses the physiology and behavior of the circadian clock. However, little is known about the effect of dopamine and dopamine receptors, especially D1-like dopamine receptors (D1Rs), in regulating the circadian rhythm and the SCN neuron's activity. Therefore, the present study aimed to investigate the role of the D1Rs in SCN neural oscillations during the 24-h light-dark cycle using local field potential (LFP) recording. To this end, two groups of rats were given the SKF-38393 (1mg/kg; i.p.) as a D1-like receptor agonist in the morning or night. LFP recording was performed for ten minutes before and two hours after the SKF-38393 injection. The obtained results showed that diurnal changes affect LFP oscillations so that delta relative power declined substantially, whereas upper-frequency bands and Lempel-Ziv complexity (LZC) index increased at night, which is consistent with rodents' activity cycles. The D1Rs agonist administration in the morning dramatically altered these intrinsic oscillations, decreasing delta and theta relative power, and most of the higher frequency bands and LZC index were promoted. Some of these effects were reversed at the night after the SKF-38393 injection. In conclusion, findings showed that the SCN's neuronal activities are regulated based on the light-dark cycle in terms of population neural oscillatory activity which could be affected by dopaminergic stimulation in a time-dependent way.

Postnatal Maturation of Membrane Potential Dynamics during in Vivo Hippocampal Ripples.

Sharp-wave ripples (SWRs) are transient high-frequency oscillations of local field potentials (LFPs) in the hippocampus and play a critical role in memory consolidation. During SWRs, CA1 pyramidal cells exhibit rapid spike sequences that often replay the sequential activity that occurred during behavior. This temporally organized firing activity gradually emerges during 2 weeks after the eye opening; however, it remains unclear how the organized spikes during SWRs mature at the intracellular membrane potential (Vm) level. Here, we recorded Vm of CA1 pyramidal cells simultaneously with hippocampal LFPs from anesthetized immature mice of either sex after the developmental emergence of SWRs. On postnatal days 16 and 17, Vm dynamics around SWRs were premature, characterized by prolonged depolarizations without either pre- or post-SWR hyperpolarizations. The biphasic hyperpolarizations, features typical of adult SWR-relevant Vm, formed by approximately postnatal day 30. This Vm maturation was associated with an increase in SWR-associated inhibitory inputs to pyramidal cells. Thus, the development of SWR-relevant inhibition restricts the temporal windows for spikes of pyramidal cells and allows CA1 pyramidal cells to organize their spike sequences during SWRs.SIGNIFICANCE STATEMENT Sharp-wave ripples (SWRs) are prominent hippocampal oscillations and play a critical role in memory consolidation. During SWRs, hippocampal neurons synchronously emit spikes with organized temporal patterns. This temporal structure of spikes during SWRs develops during the third and fourth postnatal weeks, but the underlying mechanisms are not well understood. Here, we recorded in vivo membrane potentials from hippocampal neurons in premature mice and suggest that the maturation of SWR-associated inhibition enables hippocampal neurons to produce precisely controlled spike times during SWRs.