Dynamics of spike transmission and suppression between principal cells and interneurons in the hippocampus and entorhinal cortex.

Synaptic excitation and inhibition are essential for neuronal communication. However, the variables that regulate synaptic excitation and inhibition in the intact brain remain largely unknown. Here, we examined how spike transmission and suppression between principal cells (PCs) and interneurons (INTs) are modulated by activity history, brain state, cell type, and somatic distance between presynaptic and postsynaptic neurons by applying cross-correlogram analyses to datasets recorded from the dorsal hippocampus and medial entorhinal cortex (MEC) of 11 male behaving and sleeping Long Evans rats. The strength, temporal delay, and brain-state dependency of the spike transmission and suppression depended on the subregions/layers. The spike transmission probability of PC-INT excitatory pairs that showed short-term depression versus short-term facilitation was higher in CA1 and lower in CA3. Likewise, the intersomatic distance affected the proportion of PC-INT excitatory pairs that showed short-term depression and facilitation in the opposite manner in CA1 compared with CA3. The time constant of depression was longer, while that of facilitation was shorter in MEC than in CA1 and CA3. During sharp-wave ripples, spike transmission showed a larger gain in the MEC than in CA1 and CA3. The intersomatic distance affected the spike transmission gain during sharp-wave ripples differently in CA1 versus CA3. A subgroup of MEC layer 3 (EC3) INTs preferentially received excitatory inputs from and inhibited MEC layer 2 (EC2) PCs. The EC2 PC-EC3 INT excitatory pairs, most of which showed short-term depression, exhibited higher spike transmission probabilities than the EC2 PC-EC2 INT and EC3 PC-EC3 INT excitatory pairs. EC2 putative stellate cells exhibited stronger spike transmission to and received weaker spike suppression from EC3 INTs than EC2 putative pyramidal cells. This study provides detailed comparisons of monosynaptic interaction dynamics in the hippocampal-entorhinal loop, which may help to elucidate circuit operations.

CA3 Circuit Model Compressing Sequential Information in Theta Oscillation and Replay.

The hippocampus plays a critical role in the compression and retrieval of sequential information. During wakefulness, it achieves this through theta phase precession and theta sequences. Subsequently, during periods of sleep or rest, the compressed information reactivates through sharp-wave ripple events, manifesting as memory replay. However, how these sequential neuronal activities are generated and how they store information about the external environment remain unknown. We developed a hippocampal cornu ammonis 3 (CA3) computational model based on anatomical and electrophysiological evidence from the biological CA3 circuit to address these questions. The model comprises theta rhythm inhibition, place input, and CA3-CA3 plastic recurrent connection. The model can compress the sequence of the external inputs, reproduce theta phase precession and replay, learn additional sequences, and reorganize previously learned sequences. A gradual increase in synaptic inputs, controlled by interactions between theta-paced inhibition and place inputs, explained the mechanism of sequence acquisition. This model highlights the crucial role of plasticity in the CA3 recurrent connection and theta oscillational dynamics and hypothesizes how the CA3 circuit acquires, compresses, and replays sequential information.

Oscillation-Driven Memory Encoding, Maintenance, and Recall in an Entorhinal-Hippocampal Circuit Model.

During the execution of working memory tasks, task-relevant information is processed by local circuits across multiple brain regions. How this multiarea computation is conducted by the brain remains largely unknown. To explore such mechanisms in spatial working memory, we constructed a neural network model involving parvalbumin-positive, somatostatin-positive, and vasoactive intestinal polypeptide-positive interneurons in the hippocampal CA1 and the superficial and deep layers of medial entorhinal cortex (MEC). Our model is based on a hypothesis that cholinergic modulations differently regulate information flows across CA1 and MEC at memory encoding, maintenance, and recall during delayed nonmatching-to-place tasks. In the model, theta oscillation coordinates the proper timing of interactions between these regions. Furthermore, the model predicts that MEC is engaged in decoding as well as encoding spatial memory, which we confirmed by experimental data analysis. Thus, our model accounts for the neurobiological characteristics of the cross-area information routing underlying working memory tasks.

Hippocampal Reactivation Extends for Several Hours Following Novel Experience.

New memories are believed to be consolidated over several hours of post-task sleep. The reactivation or "replay" of hippocampal cell assemblies has been proposed to provide a key mechanism for this process. However, previous studies have indicated that such replay is restricted to the first 10-30 min of post-task sleep, suggesting that it has a limited role in memory consolidation. We performed long-duration recordings in sleeping and behaving male rats and applied methods for evaluating the reactivation of neurons in pairs as well as in larger ensembles while controlling for the continued activation of ensembles already present during pre-task sleep ("preplay"). We found that cell assemblies reactivate for up to 10 h, with a half-maximum timescale of ∼6 h, in sleep following novel experience, even when corrected for preplay. We further confirmed similarly prolonged reactivation in post-task sleep of rats in other datasets that used behavior in novel environments. In contrast, we saw limited reactivation in sleep following behavior in familiar environments. Overall, our findings reconcile the duration of replay with the timescale attributed to cellular memory consolidation and provide strong support for an integral role of replay in memory.SIGNIFICANCE STATEMENT Neurons that are active during an experience reactivate again afterward during rest and sleep. This replay of ensembles of neurons has been proposed to help strengthen memories, but it has also been reported that replay occurs only in the first 10-30 min of sleep, suggesting a circumscribed role. We performed long-duration recordings in the hippocampus of rats and found that replay persists for several hours in sleep following novel experience, far beyond the limits found in previous reports based on shorter recordings. These findings reconcile the duration of replay with the hours-long timescales attributed to memory consolidation.

PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.

Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P < 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P < 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P < 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.

The log-dynamic brain: how skewed distributions affect network operations.

We often assume that the variables of functional and structural brain parameters - such as synaptic weights, the firing rates of individual neurons, the synchronous discharge of neural populations, the number of synaptic contacts between neurons and the size of dendritic boutons - have a bell-shaped distribution. However, at many physiological and anatomical levels in the brain, the distribution of numerous parameters is in fact strongly skewed with a heavy tail, suggesting that skewed (typically lognormal) distributions are fundamental to structural and functional brain organization. This insight not only has implications for how we should collect and analyse data, it may also help us to understand how the different levels of skewed distributions - from synapses to cognition - are related to each other.

A Comparison of Visual Response Properties in the Lateral Geniculate Nucleus and Primary Visual Cortex of Awake and Anesthetized Mice.

The cerebral cortex of the mouse has become one of the most important systems for studying information processing and the neural correlates of behavior. Multiple studies have examined the first stages of visual cortical processing: primary visual cortex (V1) and its thalamic inputs from the dorsal lateral geniculate nucleus (dLGN), but more rarely in the lateral posterior nucleus (LP) in mice. Multiple single-unit surveys of dLGN and V1, both with electrophysiology and two-photon calcium imaging, have described receptive fields in anesthetized animals. Increasingly, awake animals are being used in physiological studies, so it is important to compare neuronal responses between awake and anesthetized state. We have performed a comprehensive survey of spatial and temporal response properties in V1, dLGN, and lateral posterior nucleus of both anesthetized and awake animals, using a common set of stimuli: drifting sine-wave gratings spanning a broad range of spatial and temporal parameters, and sparse noise stimuli consisting of flashed light and dark squares. Most qualitative receptive field parameters were found to be unchanged between the two states, such as most aspects of spatial processing, but there were significant differences in several parameters, most notably in temporal processing. Compared with anesthetized animals, the temporal frequency that evoked the peak response was shifted toward higher values in the dLGN of awake mice and responses were more sustained. Further, the peak response to a flashed stimulus was earlier in all three areas. Overall, however, receptive field properties in the anesthetized animal remain a good model for those in the awake animal. SIGNIFICANCE STATEMENT: The primary visual cortex (V1) of the mouse and its inputs from visual thalamus (dLGN), have become a dominant model for studying information processing in the brain. Early surveys of visual response properties (receptive fields) were performed in anesthetized animals. Although most recent studies of V1 have been performed in awake animals to examine links between vision and behavior, there have been few comprehensive studies of receptive field properties in the awake mouse, especially in dLGN and lateral posterior nucleus. We have performed a comparative survey of receptive fields in dLGN, lateral posterior nucleus, and V1 in anesthetized and awake mice. We found multiple differences in processing of time-varying stimuli, whereas the spatial aspects of receptive fields remain comparatively unchanged.

Millisecond timescale synchrony among hippocampal neurons.

Inhibitory neurons in cortical circuits play critical roles in composing spike timing and oscillatory patterns in neuronal activity. These roles in turn require coherent activation of interneurons at different timescales. To investigate how the local circuitry provides for these activities, we applied resampled cross-correlation analyses to large-scale recordings of neuronal populations in the cornu ammonis 1 (CA1) and CA3 regions of the hippocampus of freely moving rats. Significant counts in the cross-correlation of cell pairs, relative to jittered surrogate spike-trains, allowed us to identify the effective couplings between neurons in CA1 and CA3 hippocampal regions on the timescale of milliseconds. In addition to putative excitatory and inhibitory monosynaptic connections, we uncovered prominent millisecond timescale synchrony between cell pairs, observed as peaks in the central 0 ms bin of cross-correlograms. This millisecond timescale synchrony appeared to be independent of network state, excitatory input, and γ oscillations. Moreover, it was frequently observed between cells of differing putative interneuronal type, arguing against gap junctions as the sole underlying source. Our observations corroborate recent in vitro findings suggesting that inhibition alone is sufficient to synchronize interneurons at such fast timescales. Moreover, we show that this synchronous spiking may cause stronger inhibition and rebound spiking in target neurons, pointing toward a potential function for millisecond synchrony of interneurons in shaping and affecting timing in pyramidal populations within and downstream from the circuit.

Comparison of sleep spindles and theta oscillations in the hippocampus.

Several network patterns allow for information exchange between the neocortex and the entorhinal-hippocampal complex, including theta oscillations and sleep spindles. How neurons are organized in these respective patterns is not well understood. We examined the cellular-synaptic generation of sleep spindles and theta oscillations in the waking rat and during rapid eye movement (REM) sleep by simultaneously recording local field and spikes in the regions and layers of the hippocampus and entorhinal cortex (EC). We show the following: (1) current source density analysis reveals that similar anatomical substrates underlie spindles and theta in the hippocampus, although the hippocampal subregions are more synchronized during spindles than theta; (2) the spiking of putative principal cells and interneurons in the CA1, CA3, and dentate gyrus subregions of the hippocampus, as well as layers 2, 3, and 5 of medial EC, are significantly phase locked to spindles detected in CA1; (3) the relationship between local field potential (LFP) phase and unit spiking differs between spindles and theta; (4) individual hippocampal principal cells generally do not fire in a rhythmic manner during spindles; (5) power in gamma (30-90 Hz) and epsilon (>90 Hz) bands of hippocampal LFP is modulated by the phase of spindle oscillations; and (6) unit firing rates during spindles were not significantly affected by whether spindles occurred during non-REM or transitions between non-REM and REM sleep. Thus, despite the similar current generator inputs and macroscopic appearance of the LFP, the organization of neuronal firing patterns during spindles bears little resemblance to that of theta oscillations.

Distinct manifold encoding of navigational information in the subiculum and hippocampus.

The subiculum (SUB) plays a crucial role in spatial navigation and encodes navigational information differently from the hippocampal CA1 area. However, the representation of subicular population activity remains unknown. Here, we investigated the neuronal population activity recorded extracellularly from the CA1 and SUB of rats performing T-maze and open-field tasks. The trajectory of population activity in both areas was confined to low-dimensional neural manifolds homoeomorphic to external space. The manifolds conveyed position, speed, and future path information with higher decoding accuracy in the SUB than in the CA1. The manifolds exhibited common geometry across rats and regions for the CA1 and SUB and between tasks in the SUB. During post-task ripples in slow-wave sleep, population activity represented reward locations/events more frequently in the SUB than in CA1. Thus, the CA1 and SUB encode information distinctly into the neural manifolds that underlie navigational information processing during wakefulness and sleep.

Cross-frequency phase-phase coupling between θ and γ 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 gamma(S) (gamma(S); 30-50 Hz), midfrequency gamma(M) (gamma(M); 50-90 Hz), and fast gamma(F) (gamma(F); 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 gamma(S) and gamma(M) but not gamma(F) oscillators. We suggest that cross-frequency phase coupling can support multiple time-scale control of neuronal spikes within and across structures.

Functional connectivity and tuning curves in populations of simultaneously recorded neurons.

How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves. Modeling functional interactions improves both encoding and decoding accuracy by accounting for noise correlations and features of the external world that tuning curves fail to capture. In cortex, modeling coupling alone allows spikes to be predicted more accurately than tuning curve models based on external variables. These results suggest that statistical models of functional interactions between even relatively small numbers of neurons may provide a useful framework for examining neural coding.

Temporal delays among place cells determine the frequency of population theta oscillations in the hippocampus.

Driven either by external landmarks or by internal dynamics, hippocampal neurons form sequences of cell assemblies. The coordinated firing of these active cells is organized by the prominent "theta" oscillations in the local field potential (LFP): place cells discharge at progressively earlier theta phases as the rat crosses the respective place field ("phase precession"). The faster oscillation frequency of active neurons and the slower theta LFP, underlying phase precession, creates a paradox. How can faster oscillating neurons comprise a slower population oscillation, as reflected by the LFP? We built a mathematical model that allowed us to calculate the population activity analytically from experimentally derived parameters of the single neuron oscillation frequency, firing field size (duration), and the relationship between within-theta delays of place cell pairs and their distance representations ("compression"). The appropriate combination of these parameters generated a constant frequency population rhythm along the septo-temporal axis of the hippocampus, while allowing individual neurons to vary their oscillation frequency and field size. Our results suggest that the faster-than-theta oscillations of pyramidal cells are inherent and that phase precession is a result of the coordinated activity of temporally shifted cell assemblies, relative to the population activity, reflected by the LFP.

Fast network oscillations during non-REM sleep support memory consolidation.

The neocortex is disconnected from the outside world during sleep, which has been hypothesized to be relevant for synaptic reorganization involved in memory consolidation. Fast network oscillations, such as hippocampal sharp-wave ripples, cortical ripples, and amygdalar high-frequency oscillations, are prominent during non-REM sleep. Although these oscillations are thought to be generated by local circuit mechanisms, their occurrence rates and amplitudes are modulated by thalamocortical spindles and neocortical slow oscillations during non-REM sleep, suggesting that fast network oscillations and slower oscillations cooperatively work to facilitate memory consolidation. This review discusses the recent progress in understanding the generation, coordination, and functional roles of fast network oscillations. Further, it outlines how fast network oscillations in distinct brain regions synergistically support memory consolidation and retrieval by hosting cross-regional coactivation of memory-related neuronal ensembles.

Impact of tumoral structure and bacterial species on growth and biodistribution of live bacterial therapeutics in xenografted tumours.

Live bacterial therapeutics is gaining attention, especially for cancer therapy, because anaerobic bacteria selectively grow inside the solid tumours. However, the effect of tumour structure and bacterial characteristics on the pharmacokinetics of tumours is unclear; therefore, we aimed to elucidate the effects of tumour structure and types of bacteria on tumoral bacterial growth. Using six mouse xenograft models, including stroma-rich tumours similar to clinical tumours, and two models of live bacterial therapeutics, Salmonella typhimurium VNP20009 and Escherichia coli DH5α, we investigated bacterial growth and distribution in tumours after intravenous administration. Rapid growth of E. coli was observed in HCT116 and other tumours with few collagens, blood vessels not covered by mural cells, and a cancer cell area proliferated disorderly, whereas tumours with contrasting features, such as BxPC-3, showed lower bacterial growth and a limited intratumor distribution. Alternatively, Salmonella typhimurium VNP20009, when successfully proliferated (the probability was approximately 50%), grew to 108 colony forming units/g tissue even in BxPC-3 tumours, and its intratumor distribution was extensive. This study suggests that the development of new methods to modify tumour structure will be essential for the development of anti-tumour clinical therapies based on live bacterial therapeutics.

A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice.

Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (µ)-electrocorticography (µECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped µECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current µECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel µECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the µECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the µECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our µECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.

Relationships between hippocampal sharp waves, ripples, and fast gamma oscillation: influence of dentate and entorhinal cortical activity.

Hippocampal sharp waves (SPWs) and associated fast ("ripple") oscillations (SPW-Rs) in the CA1 region are among the most synchronous physiological patterns in the mammalian brain. Using two-dimensional arrays of electrodes for recording local field potentials and unit discharges in freely moving rats, we studied the emergence of ripple oscillations (140-220 Hz) and compared their origin and cellular-synaptic mechanisms with fast gamma oscillations (90-140 Hz). We show that (1) hippocampal SPW-Rs and fast gamma oscillations are quantitatively distinct patterns but involve the same networks and share similar mechanisms; (2) both the frequency and magnitude of fast oscillations are positively correlated with the magnitude of SPWs; (3) during both ripples and fast gamma oscillations the frequency of network oscillation is higher in CA1 than in CA3; and (4) the emergence of CA3 population bursts, a prerequisite for SPW-Rs, is biased by activity patterns in the dentate gyrus and entorhinal cortex, with the highest probability of ripples associated with an "optimum" level of dentate gamma power. We hypothesize that each hippocampal subnetwork possesses distinct resonant properties, tuned by the magnitude of the excitatory drive.

Activity dynamics and behavioral correlates of CA3 and CA1 hippocampal pyramidal neurons.

The CA3 and CA1 pyramidal neurons are the major principal cell types of the hippocampus proper. The strongly recurrent collateral system of CA3 cells and the largely parallel-organized CA1 neurons suggest that these regions perform distinct computations. However, a comprehensive comparison between CA1 and CA3 pyramidal cells in terms of firing properties, network dynamics, and behavioral correlations is sparse in the intact animal. We performed large-scale recordings in the dorsal hippocampus of rats to quantify the similarities and differences between CA1 (n > 3,600) and CA3 (n > 2,200) pyramidal cells during sleep and exploration in multiple environments. CA1 and CA3 neurons differed significantly in firing rates, spike burst propensity, spike entrainment by the theta rhythm, and other aspects of spiking dynamics in a brain state-dependent manner. A smaller proportion of CA3 than CA1 cells displayed prominent place fields, but place fields of CA3 neurons were more compact, more stable, and carried more spatial information per spike than those of CA1 pyramidal cells. Several other features of the two cell types were specific to the testing environment. CA3 neurons showed less pronounced phase precession and a weaker position versus spike-phase relationship than CA1 cells. Our findings suggest that these distinct activity dynamics of CA1 and CA3 pyramidal cells support their distinct computational roles.

Oscillation-coordinated, noise-resistant information distribution via the subiculum.

The hippocampus processes information associated with spatial navigation. The subiculum receives input from the hippocampus CA1 and projects to various cortical and subcortical regions. Thus, the subiculum is uniquely positioned to distribute hippocampal information to a range of brain areas. Subicular neurons fire at higher rates than CA1 neurons and exhibit similarly or more accurately decodable representations of place, speed, and trajectory. These representations are more noise-resistant and advantageous for long-range information transfer. Subicular neurons selectively or uniformly distribute information to target areas, depending on the information type. Theta oscillations and sharp-wave ripples control information broadcasting in a pathway-specific manner. Thus, the subiculum routes accurately decodable, noise-resistant, navigation-associated information to downstream regions.

De novo inter-regional coactivations of preconfigured local ensembles support memory.

Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fear memory; however, how inter-regional ensemble interactions support memory remains elusive. Using multi-regional large-scale electrophysiology in the aforementioned structures of fear-conditioned rats, we found that the local ensembles activated during fear memory acquisition are inter-regionally coactivated during the subsequent sleep period, which relied on brief bouts of fast network oscillations. During memory retrieval, the coactivations reappeared, together with fast oscillations. Coactivation-participating-ensembles were configured prior to memory acquisition in the amygdala and prefrontal cortex but developed through experience in the hippocampus. Our findings suggest that elements of a given memory are instantly encoded within various brain regions in a preconfigured manner, whereas hippocampal ensembles and the network for inter-regional integration of the distributed information develop in an experience-dependent manner to form a new memory, which is consistent with the hippocampal memory index hypothesis.