Temporal Encoding of Place Sequences by Hippocampal Cell Assemblies

SummaryBoth episodic memory and spatial navigation require temporal encoding of the relationships between events or locations. In a linear maze, ordered spatial distances between sequential locations were represented by the temporal relations of hippocampal place cell pairs within cycles of theta oscillation in a compressed manner. Such correlations could arise due to spike “phase precession” of independent neurons driven by common theta pacemaker or as a result of temporal coordination among specific hippocampal cell assemblies. We found that temporal correlation between place cell pairs was stronger than predicted by a pacemaker drive of independent neurons, indicating a critical role for synaptic interactions and precise timing within and across cell assemblies in place sequence representation. CA1 and CA3 ensembles, identifying spatial locations, were active preferentially on opposite phases of theta cycles. These observations suggest that interleaving CA3 neuronal sequences bind CA1 assemblies representing overlapping past, present, and future locations into single episodes

Inhibition and Brain Work

The major part of the brain's energy budget (∼60%–80%) is devoted to its communication activities. While inhibition is critical to brain function, relatively little attention has been paid to its metabolic costs. Understanding how inhibitory interneurons contribute to brain energy consumption (brain work) is not only of interest in understanding a fundamental aspect of brain function but also in understanding functional brain imaging techniques which rely on measurements related to blood flow and metabolism. Herein we examine issues relevant to an assessment of the work performed by inhibitory interneurons in the service of brain function

The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes

Neuronal activity in the brain gives rise to transmembrane currents that can be measured in the extracellular medium. Although the major contributor of the extracellular signal is the synaptic transmembrane current, other sources — including Na+ and Ca2+ spikes, ionic fluxes through voltage- and ligand-gated channels, and intrinsic membrane oscillations — can substantially shape the extracellular field. High-density recordings of field activity in animals and subdural grid recordings in humans, combined with recently developed data processing tools and computational modelling, can provide insight into the cooperative behaviour of neurons, their average synaptic input and their spiking output, and can increase our understanding of how these processes contribute to the extracellular signal

Temporal coupling of field potentials and action potentials in the neocortex

The local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years, investigators have found that action potential firing rates increase during elevations in power high‐frequency band oscillations (50–200 Hz range). However, action potentials also contribute to the LFP signal itself, making the spike–LFP relationship complex. Here, we examine the relationship between spike rates and LFP in varying frequency bands in rat neocortical recordings. We find that 50–180 Hz oscillations correlate most consistently with high firing rates, but that other LFP bands also carry information relating to spiking, including in some cases anti‐correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation‐based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.We examined the relationship between spike rates and local field potentials (LFP) in the rat neocortex, and we find that while 50–180 Hz oscillatory power correlates most consistently with firing rates of neurons, other LFP bands also carry spiking‐related information. We additionally find that spiking itself and electromyographic activity contribute to LFP power and that the ratio of excitatory to inhibitory activity also correlates with 50–180 Hz power. Finally, we create an improved oscillation‐based predictor of action potential activity by utilizing information from the entire LFP frequency spectrum at once.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/1/ejn13807-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/2/ejn13807-sup-0007-FigS7.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/3/ejn13807-sup-0002-FigS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/4/ejn13807-sup-0003-FigS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/5/ejn13807-sup-0005-FigS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/6/ejn13807_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/7/ejn13807-sup-0009-reviewerComments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/8/ejn13807-sup-0006-FigS6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/9/ejn13807-sup-0008-FigS8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/10/ejn13807.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146325/11/ejn13807-sup-0004-FigS4.pd

Single-Trial Phase Precession in the Hippocampus

During the crossing of the place field of a pyramidal cell in the rat hippocampus, the firing phase of the cell decreases with respect to the local theta rhythm. This phase precession is usually studied on the basis of data in which many place field traversals are pooled together. Here we study properties of phase precession in single trials. We found that single-trial and pooled-trial phase precession were different with respect to phase-position correlation, phase-time correlation, and phase range. Whereas pooled-trial phase precession may span 360°, the most frequent single-trial phase range was only ∼180°. In pooled trials, the correlation between phase and position (r = −0.58) was stronger than the correlation between phase and time (r = −0.27), whereas in single trials these correlations (r = −0.61 for both) were not significantly different. Next, we demonstrated that phase precession exhibited a large trial-to-trial variability. Overall, only a small fraction of the trial-to-trial variability in measures of phase precession (e.g., slope or offset) could be explained by other single-trial properties (such as running speed or firing rate), whereas the larger part of the variability remains to be explained. Finally, we found that surrogate single trials, created by randomly drawing spikes from the pooled data, are not equivalent to experimental single trials: pooling over trials therefore changes basic measures of phase precession. These findings indicate that single trials may be better suited for encoding temporally structured events than is suggested by the pooled data

Role of Hippocampal CA2 Region in Triggering Sharp-Wave Ripples

Sharp-wave ripples (SPW-Rs) in the hippocampus are implied in memory consolidation, as shown by observational and interventional experiments. However, the mechanism of their generation remains unclear. Using two-dimensional silicon probe arrays, we investigated the propagation of SPW-Rs across the hippocampal CA1, CA2, and CA3 subregions. Synchronous activation of CA2 ensembles preceded SPW-R-related population activity in CA3 and CA1 regions. Deep CA2 neurons gradually increased their activity prior to ripples and were suppressed during the population bursts of CA3-CA1 neurons (ramping cells). Activity of superficial CA2 cells preceded the activity surge in CA3-CA1 (phasic cells). The trigger role of the CA2 region in SPW-R was more pronounced during waking than sleeping. These results point to the CA2 region as an initiation zone for SPW-Rs

Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats

Low intensity electric fields have been suggested to affect the ongoing neuronal activity in vitro and in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performed in vivo extracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity

Closed-loop control of epilepsy by transcranial electrical stimulation

Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients.Fil: Berényi, Antal. Rutgers University; Estados Unidos. University of New York; Estados Unidos. University of Szeged; HungríaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Rutgers University; Estados UnidosFil: Mao, Dun. Rutgers University; Estados UnidosFil: Buzsáki, György. Rutgers University; Estados Unidos. University of New York; Estados Unido

Cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

Neuronal oscillations allow for temporal segmentation of neuronal spikes. Interdependent oscillators can integrate multiple layers of information. We examined phase–phase coupling of theta and gamma oscillators in the CA1 region of rat hippocampus during maze exploration and rapid eye movement sleep. Hippocampal theta waves were asymmetric, and estimation of the spatial position of the animal was improved by identifying the waveform-based phase of spiking, compared to traditional methods used for phase estimation. Using the waveform-based theta phase, three distinct gamma bands were identified: slow gammaS (gammaS; 30–50 Hz), midfrequency gammaM (gammaM; 50–90 Hz), and fast gammaF (gammaF; 90–150 Hz or epsilon band). The amplitude of each sub-band was modulated by the theta phase. In addition, we found reliable phase–phase coupling between theta and both gammaS and gammaM but not gammaF oscillators. We suggest that cross-frequency phase coupling can support multiple time-scale control of neuronal spikes within and across structures.Fil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mizuseki, Kenji. Rutgers University; Estados UnidosFil: Schmidt, Robert. Rutgers University; Estados UnidosFil: Kempter, Richard. Rutgers University; Estados UnidosFil: Buzsáki, György. Rutgers University; Estados Unido