Biology subjects

Mohajerani, M. H.

Publications and source records attributed to Mohajerani, M. H..

At least 19 recordsLinked to original sources

bioRxiv2026

Ecological Suboptimality in Naturalistic Foraging: Amplified Deviation from Optimality in a Mouse Model of Alzheimer Disease

Adaptive decision-making extends beyond selecting among discrete alternatives. It requires the dynamic organization of actions as costs, opportunities, and goals evolve over time. Foraging captures this complexity in an evolutionarily conserved behavior that integrates spatial, temporal, and reward-related information across successive actions. These demands make foraging an ecologically grounded framework for investigating Alzheimer disease, in which spatial cognition, temporal organization, cost evaluation, and behavioral flexibility are frequently disrupted. We examined foraging-related action selection in control C57BL/6J mice and APPNL-G-F knock-in mice using a controlled task in which travel distance, food texture, and pellet size altered the costs and benefits of available strategies. Bayesian multinomial modeling showed that control mice flexibly redistributed their behavior across conditions, whereas APPNL-G-F mice showed impaired cost integration, increased withdrawal, and reduced behavioral flexibility rather than a generalized performance impairment. Comparison with a classical reward-rate-maximization benchmark revealed substantial suboptimality in both groups. Control mice achieved 53% of the predicted optimal reward rate, whereas APPNL-G-F mice achieved 45%. These systematic departures suggest that behavior was shaped by cognitive, motivational, or contextual constraints not represented in the normative model, with Alzheimer-disease-relevant dysfunction associated with greater suboptimality. Group differences were greatest when optimal behavior was highly sensitive to competing costs. By preserving the distribution of behavior across strategies, this study establishes foraging-related action selection as a sensitive framework for detecting disease-associated disruptions that may be obscured by conventional measures of choice or overall task performance.

neuroscience↗

bioRxiv2026

Differential adenosine to inosine RNA editing of SINE B2 non-coding RNAs in mouse unveils a novel type of epi-transcriptome response to amyloid beta neuro-toxicity

Alzheimers disease (AD) is characterized by early molecular responses to amyloid beta neuro-toxicity that remain poorly defined. RNA editing by adenosine-to-inosine (A-to-I) conversion is a major epitranscriptomic mechanism, yet its contribution to non-coding RNA regulation during neurodegeneration is largely unknown. Short Interspersed Nuclear Element (SINE)-derived RNAs, including mouse B2 RNAs, represent the dominant substrates of A-to-I editing and have recently been shown to regulate gene expression through ribozyme-mediated processing. Here, we introduce and validate a repeat-aware bioinformatics framework that enables position-specific quantification of A-to-I editing within highly repetitive SINE RNAs--an analysis that has been challenging using standard genome-based pipelines. Applying this approach, we uncover discrete editing hotspots in B2 RNAs whose modification is selectively increased during the earliest stages of amyloid beta pathology. Elevated B2 RNA editing is consistently observed across hippocampal or neocortical tissue from two independent mouse models of amyloid beta accumulation and in hippocampal neurons exposed to acute amyloid beta toxicity. Functional perturbation of ADAR activity alters both B2 RNA editing levels and the expression of B2 RNA regulated stress-response genes, directly linking RNA editing to SINE-mediated transcriptional control. Independent validation using Nanopore direct RNA sequencing indicates increased RNA modification signals at the same B2 RNA regions identified by short-read Illumina sequencing. Together, our findings establish a previously unrecognized epitranscriptomic response to amyloid beta neurotoxicity mediated by site-specific A-to-I editing of SINE RNAs. This work defines a new analytical paradigm for studying RNA editing in RNAs from repetitive elements and reveals a regulatory axis connecting amyloid beta toxicity, ADAR activity, SINE RNA editing, and stress-responsive gene expression, with implications for conserved mechanisms underlying Alzheimers disease and related neurodegenerative disorders.

bioinformatics↗

bioRxiv2025

DISTINCT NEURAL SIGNATURES OF HIPPOCAMPAL POPULATION DYNAMICS DURING LOCOMOTION-IN-PLACE

Hippocampal CA1 neurons modulate their activity with movement variables such as time, distance, and speed, yet it remains unclear how these representations reorganize across behavioral states, from externally driven to self-paced movement and immobility. Here, we investigated how sensory events that initiate or terminate locomotion, structure CA1 population codes and how these codes reorganize across sensory-driven locomotion, spontaneous locomotion, and forced immobility. Using two-photon calcium imaging in head-fixed Thy1-GCaMP mice (n = 5) performing the air-induced running task on a non-motorized conveyor belt, we examined neuronal firing-rate modulation across a series of behavioral configurations designed to probe distinct forms of locomotion-in-place. In the No-Brake (locomotion-permitted) condition, the belt rotated freely, allowing animals to execute full cyclic limb movements in response to air stimulation. In the Brake (immobility) condition, the belt was fixed, restricting movement to partial or attempted locomotor motions. Firing-rate modulation with respect to time, distance, and speed was quantified using linear (Pearson correlation) and nonlinear (mutual information) metrics under permutation testing in the natural reference domains. Behaviorally, air stimuli produced faster, sustained running during air-on and more variable, self-paced movement during air-off. Neurally, a larger fraction of CA1 cells was active and significantly modulated during air-off. Within the modulated set, singularly tuned cells (time, distance, or speed) predominated over mixed-tuned cells, and speed-modulated cells peaked earlier after stimulus onset or offset than time- or distance-modulated cells. Under Brake, CA1 activity was predominantly singularly tuned to time or movement-in-place, with stronger movement modulation and engagement post-stimulation. Despite substantial single-cell turnover across configurations and phases, population-level analyses revealed a coherent, air-phase-locked organization and distinct movement-related populations across Brake and No-Brake conditions. These results indicate a state-dependent reweighting of sensorimotor features implemented atop a conserved ensemble scaffold in CA1.

neuroscience↗

bioRxiv2023

Spatiotemporal resonance in mouse primary visual cortex

Human primary visual cortex (V1) responds more strongly, or resonates, when exposed to [~]10, [~]15-20, [~]40-50 Hz rhythmic flickering light. Full-field flicker also evokes perception of hallucinatory geometric patterns, which mathematical models explain as standing-wave formations emerging from periodic forcing at resonant frequencies of the simulated neural network. However, empirical evidence for such flicker-induced standing waves in the visual cortex was missing. We recorded cortical responses to flicker in awake mice using high spatial resolution widefield imaging in combination with high temporal resolution glutamate-sensing fluorescent reporter (iGluSnFR). The temporal frequency tuning curves in the mouse V1 were similar to those observed in humans, showing a banded structure with multiple resonance peaks (8 Hz, 15 Hz, 33 Hz). Spatially, all flicker frequencies evoked responses in V1 corresponding to retinotopic stimulus location, but some evoked additional peaks. These flicker-induced cortical patterns displayed standing wave characteristics and matched linear wave equation solutions in an area restricted to the visual cortex. Taken together, the interaction of periodic traveling waves with cortical area boundaries leads to spatiotemporal activity patterns that may affect perception.

neuroscience↗

bioRxiv2022

Cortical Reactivation of Non-Spatial and Spatial Memory Representations Coordinate with Hippocampus to Form a Memory Dialogue

Episodic memory depends on the association of diverse attribute representations that are distributed across the neocortex, and evidence suggests that these attributes are linked, at least initially, by the hippocampus, which orchestrates retrieval and the offline replay of experience during memory consolidation. The dynamics that characterize this hippocampal-cortical dialogue, however, are only partly understood. Although it was originally proposed that replay is initiated in CA3, with the spontaneous emission of sharp-wave ripple (SWR) bursts, increasing evidence suggests that cortex may seed the process with partial information, leading to pattern completion in CA3 and subsequent global reactivation of the episode. A recent study has shown that the secondary motor cortex (M2), among other areas, carries two distinct types of representations: place cell-like activity, which relies on an intact hippocampus for its development, and responses tied to visuo-tactile cues -- the attributes of the experience, which do not require the hippocampus. Using two-photon Ca2+ imaging, while simultaneously acquiring LFP from the ipsilateral CA1, we assessed the interactions among cortical retrieval of visuo-tactile attributes of previous experiences in a virtual environment, hippocampal SWR, and the cortical reinstatement of the spatial aspects of the same experiences. During rest after the experience, two types of reactivation events occurred, which separately conveyed information about spatial trajectories and visuo-tactile attributes. Reactivation of attribute information preceded that of trajectories in relation to hippocampal SWRs. Furthermore, paired reactivations of cue and trajectory information supported similar features of previous experiences. These results are consistent with the hypothesis that cortical retrieval of non-spatial attributes of recent experience seeds hippocampal reactivation of associated spatial sequences, which is followed by retrieval of episodic memory traces.

neuroscience↗

bioRxiv2022

Generation of a hybrid AppNL-G-F/NL-G-F xThy1-GCaMP6s+/- Alzheimer disease mouse mitigates the behavioral and hippocampal encoding deficits of APP knock-in mutations of AppNL-G-F/NL-G-F mice

In contrast to most transgenic mouse models of Alzheimer disease (AD), knock-in mice expressing familial AD-linked mutations of the amyloid precursor protein (App) gene exhibit stereotypical age-dependent amyloid beta (A{beta}) pathology and cognitive impairment without physiologically unrealistic App overexpression. This study investigated the effect of familial AD-linked App mutations on hippocampal CA1 neuronal activity and function. To enable calcium imaging of neuronal activity, AppNL-G-F/NL-G-F knock-in (APPki) mice were crossed with Thy1-GCaMP6s+/- (C-TG) mice to generate AppNL-G-F/NL-G-FxThy1-GCaMP6s+/- (A-TG) mice, which were characterized at 12 months of age. A-TG mice exhibited A{beta} pathology in the hippocampus. In several configurations of an air-induced running task, A-TG mice and C-TG mice were equally successful in learning to run or to stay immobile. In the Morris water place test, A-TG mice were impaired, but learned the task. Comparisons of hippocampal CA1 neuronal activity in the air-induced running task showed that A-TG mice displayed neuronal hypoactivity both during movement and immobility. A-TG mice and C-TG CA1 neuronal encoding of distance or time in the air induced running task were not different. These results suggest that knock-in of familial AD-linked mutations in A-TG mice results in A{beta} pathology, neuronal hypoactivity, and cognitive impairment without severely affecting CA1 neuronal encoding. In comparison to APPki mice, A-TG mice had less severe AD-like memory impairments at 12 months of age (Saito et al., 2014; Mehla et al., 2019), suggesting that the disease onset was delayed in A-TG mice. The effect of APP mutations may have been mitigated through genetic mechanisms when APPKi mice were crossed with C-TG mice.

neuroscience↗

bioRxiv2022

Gradual cerebral hypoperfusion in a knock-in mouse model of Alzheimer's disease triggers cortical network dysfunctions

Alzheimers disease (AD) is characterized neuropathologically by amyloid-{beta} (A{beta}) plaques and neurofibrillary tangles. Vascular pathology caused by chronic cerebral hypoperfusion (HP) is hypothesised to exacerbate AD pathology and has emerged as an increasing cause of age-related cognitive impairment. In this study we examined the effects of gradual cerebral HP on cognitive dysfunction, A{beta} pathology, microgliosis, and cortical network dynamics in C57BL/6J mice and a single App knock-in mouse model of AD (AppNL-G-F). We performed unilateral common carotid artery gradual occlusion (UCAgO) in two-month-old mice using an ameroid constrictor. At 4 months of age, animals were tested in a behavioral battery consisting of tests of spatial learning and memory (Morris water task), recognition memory (novel object recognition task), and motor coordination (balance beam). Following behavioural testing, in vivo mesoscale wide-field voltage imaging was done to assess cortical functional connectivity and sensory-evoked cortical activity, and brains were harvested for pathology characterization using immunohistochemistry. We found that UCAgO reduced cerebral blood flow (CBF) in the occluded hemisphere (OH), however, subtle behavioural deficits were observed due to HP. A dissociative effect of HP was observed in resting-state functional connectivity analysis, where HP led to hyper-connectivity in C57 mice and hypo-connectivity in App mice. Interestingly, sensory stimulation of limbs contralateral to OH revealed hyper-cortical activations in the non-occluded hemisphere of C57 HP mice, however, hypo-cortical activations were observed in App HP mice. Furthermore, we found that the UCAgO increased cortical and hippocampal microgliosis in both hemispheres of C57 and App mice, a bilateral increase in A{beta} deposition was only observed in App mice. These results suggest that gradual cerebral HP leads to cortical network alterations in AD, which is partly mediated via activation of microglia.

neuroscience↗

bioRxiv2022

Conjunctive and complementary CA1 hippocampal cell populations relate sensory events to immobility and locomotion

This study investigated the dynamics of recruitment of cells in the CA1 region of the hippocampus in response to sensory stimuli presented during immobility, movement, and their transitions. Two-photon calcium imaging of somal activity in CA1 neuron populations was done in head fixed mice. Sensory stimuli, either a light flash or an air stream, were delivered to the mice when at rest, when moving spontaneously, and while they were induced to run a fixed distance on the conveyor belt. Overall, 99% of 2083 identified cells (from 5 mice) were active across one or more of 20 sensorimotor events. A larger proportion of cells were active during locomotion. Nevertheless, for any given sensorimotor event, only about 17% of cells were active. When considering pairs of sensorimotor event types, the active cell population consisted of conjunctive (C [isin] A and B) cells, active across both events, and complementary (C [isin] A not B or C [isin] B not A) cells that were active only during individual events. Whereas conjunctive cells characterised stable representations of repeated sensorimotor events, complementary cells characterised recruitment of new cells for encoding novel sensorimotor events. The moment-to-moment recruitment of conjunctive and complementary cells across changing sensorimotor events signifies the involvement of the hippocampus in functional networks integrating sensory information with ongoing movement. This role of the hippocampus is well suited for movement guidance that secondarily might include spatial behavior, episodic learning and memory, context representation, and scene construction.

neuroscience↗

bioRxiv2022

Amyloid-β seeding effects are dependent on the presence of knock-in genes in the AppNL-G-F mice.

Alzheimers disease (AD) is characterized by the prion-like propagation of amyloid-{beta} (A{beta}). However, the role of A{beta} in cognitive impairment is still unclear. To determine the causal role of A{beta} in AD, we intracerebrally seeded the entorhinal cortex of two-month-old AppNL-G-F mouse model with an A{beta} peptide derived from patients who died from rapidly progressing AD. When the mice were three and six months of age, or one- and four-months following seeding, respectively, spatial learning and memory were tested using the Morris water task. Immunohistochemical labeling showed seeding with the A{beta} seed increased plaque size one month following seeding, but reduced plaque counts four months following injection compared to the control seeded mice. A significant increase in microgliosis was found. However, we found no correlation between pathology and spatial performance. The results of the present study show that seeding human tissue with or without A{beta} alters learning and memory ability, A{beta} plaque deposition, plaque size, and microgliosis in the AppNL-G-F knock-in model, and these effects are dependent on the presence of a humanized App gene and the presence of A{beta} in the seed. But these pathological changes were not initially causal in memory impairment.

animal behavior and cognition↗

bioRxiv2022

Hippocampal gamma and sharp wave/ripples mediate bidirectional interactions with cortical networks during sleep

Hippocampus-neocortex interactions during sleep are critical for memory processes: hippocampally-initiated replay contributes to memory consolidation in the neocortex and hippocampal sharp wave/ripples are linked to generalized increases in neocortical cell activity and DOWN-UP state transitions. Yet, the spatial and temporal patterns of this exchange are unknown. With voltage imaging, electrocorticography, and laminarly-resolved hippocampal potentials, we characterized cortico-hippocampal interactions during anesthesia and NREM sleep. We observed neocortical activation transients spanning multiple spatial scales hinting at a quasi-critical regime. Transients were organized in a small number of functional networks matching known anatomical connectivity. A network overlapping with the default mode network and centered on retrosplenial cortex was the most associated with the hippocampus. Interestingly, hippocampal slow gamma was the oscillation that best correlated with this neocortical network, outpacing ripples. In fact, neocortical activity predicted hippocampal slow gamma and followed ripples, suggesting that consolidation processes rely on bi-directional exchanges between hippocampus and neocortex.

neuroscience↗

bioRxiv2022

Inhibition is a prevalent mode of activity in the neocortex around awake hippocampal ripples

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples.

neuroscience↗

bioRxiv2022

Regional variation in cholinergic terminal activity determines the non-uniform occurrence of cortical slow-wave activity during REM sleep

Sleep consists of two basic stages: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is characterized by slow high-amplitude cortical EEG signals, while REM sleep is characterized desynchronized cortical rhythms. While, until recently, it has been widely believed that cortical activity during REM sleep is globally desynchronized, recent electrophysiological studies showed slow waves (SW) in some cortical areas during REM sleep. Electrophysiological techniques, however, have been unable to resolve the regional structure of these activities, due to relatively sparse sampling. We mapped functional gradients in cortical activity during REM sleep using mesoscale imaging in mice, and observed local SW patterns occurring mainly in somatomotor and auditory cortical regions, with minimum presence within the default mode network. The role of the cholinergic system in local desynchronization during REM sleep was also explored by calcium imaging of cholinergic terminal activity within the mouse cortex. Terminal activity was weaker in regions exhibiting SW activity more frequently during REM sleep. We also analyzed Allen Mouse Brain Connectivity dataset and found that these regions have weaker cholinergic projections from the basal forebrain.

neuroscience↗

bioRxiv2021

Altered cortical processing of sensory input in Huntington disease mouse models

Huntington disease (HD), a hereditary neurodegenerative disorder, manifests as progressively impaired movement and cognition. Although early abnormalities of neuronal activity in striatum are well established in HD models, there are fewer in vivo studies of the cortex. Here, we record local field potentials (LFPs) in YAC128 HD model mice versus wild-type mice. In multiple cortical areas, limb sensory stimulation evokes a greater change in LFP power in YAC128 mice. Mesoscopic imaging using voltage-sensitive dyes reveal more extensive spread of evoked sensory signals across the cortical surface in YAC128 mice. YAC128 layer 2/3 sensory cortical neurons ex vivo show increased excitatory events, which could contribute to enhanced sensory responses in vivo. Cortical LFP responses to limb stimulation, visual and auditory input are also significantly increased in zQ175 HD mice. Results presented here extend knowledge of HD beyond ex vivo studies of individual neurons to the intact cortical network.

neuroscience↗

bioRxiv2020

Sensory experience selectively reorganizes the late component of evoked responses

In response to sensory stimulation, the cortex exhibits an early transient response followed by a late and slower activation pattern. Recent studies suggest that the early component represents features of the stimulus while the late component is associated with stimulus perception. Although very informative, these studies only focus on the amplitude of the evoked responses to study its relationship with sensory perception. In this work we expand upon the study of how patterns of evoked and spontaneous activity are modified by experience at mesoscale level using voltage and extracellular glutamate transient recordings over widespread regions of mice dorsal neocortex. We find that repeated tactile or auditory stimulation selectively modifies the spatiotemporal patterns of cortical activity, mainly of the late evoked response in anesthetized mice injected with amphetamine and also in awake mice. This modification lasted up to 60 minutes and results not only in an increase in amplitude of the late response after repeated stimulation, but also in an increase in the similarity between the spatiotemporal patterns of the late and the early evoked response patterns in anesthetized mice. This similarity increase occurs only for the evoked responses of the sensory modality that received the repeated stimulation. Thus, this selective long-lasting spatiotemporal modification of the cortical activity patterns might provide evidence that evoked responses are a cortex-wide phenomenon. This work opens new questions about how perception-related cortical activity changes with sensory experience across the cortex.

neuroscience↗

bioRxiv2020

Prenatal Stress Dysregulates Resting-State Functional Connectivity and Sensory Motifs

Prenatal stress (PS) can impact fetal brain structure and function and contribute to higher vulnerability to neurodevelopmental and neuropsychiatric disorders. To understand how PS alters evoked and spontaneous neocortical activity and intrinsic brain functional connectivity, mesoscale voltage imaging was performed in adult C57BL/6NJ mice that had been exposed to auditory stress on gestational days 12-16, the age at which neocortex is developing. PS mice had a four-fold higher basal corticosterone level and reduced amplitude of cortical sensory-evoked responses to visual, auditory, whisker, forelimb, and hindlimb stimuli. Relative to control animals, PS also led to a general reduction of resting-state functional connectivity, as well as reduced inter-modular connectivity, enhanced intra-modular connectivity, and altered frequency of auditory and forelimb spontaneous sensory motifs. These resting-state changes resulted in a cortical connectivity pattern featuring disjoint but tight modules and a decline in network efficiency. The findings demonstrate that cortical connectivity is sensitive to PS and exposed offspring may be at risk for adult stress-related neuropsychiatric disorders.

neuroscience↗

bioRxiv2020

Mesoscopic cortical network reorganization during recovery of partial optic nerve injury in GCaMP6s mice

As the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 30 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated at the same time points. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 30 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.

neuroscience↗

bioRxiv2020

Spatiotemporal structure of sensory-evoked and spontaneous activity revealed by mesoscale imaging in anesthetized and awake mice

Brain activity propagates across the cortex in diverse spatiotemporal patterns, both as a response to sensory stimulation and during spontaneous activity. Despite been extensively studied, the relationship between the characteristics of such patterns during spontaneous and evoked activity is not completely understood. To investigate this relationship, we compared visual, auditory, and tactile evoked activity patterns elicited with different stimulus strengths and spontaneous activity motifs in lightly anesthetized and awake mice using mesoscale wide-field voltage-sensitive dye and glutamate imaging respectively. The characteristics of cortical activity that we compared include amplitude, speed, direction, and complexity of propagation trajectories in spontaneous and evoked activity patterns. We found that the complexity of the propagation trajectories of spontaneous activity, quantified as their fractal dimension, is higher than the one from sensory evoked responses. Moreover, the speed and direction of propagation, are modulated by the amplitude during both, spontaneous and evoked activity. Finally, we found that spontaneous activity had similar amplitude and speed when compared to evoked activity elicited with low stimulus strengths. However, this similarity gradually decreased when the strength of stimuli eliciting evoked responses increased. Altogether, these findings are consistent with the fact that even primary sensory areas receive widespread inputs from other cortical regions, and that, during rest, the cortex tends to reactivate traces of complex, multi-sensory experiences that may have occurred in a range of different behavioural contexts.

neuroscience↗

bioRxiv2019

Spatiotemporal patterns of neocortical activity around hippocampal sharp-wave ripples

A prevalent model is that sharp-wave ripples (SWR) arise spontaneously in CA3 and propagate recent memory traces outward to the neocortex to facilitate memory consolidation there. Using voltage and extracellular glutamate transient recording over widespread regions of mice dorsal neocortex in relation to CA1 multiunit activity (MUA) and SWR, we find that the largest SWR-related modulation occurs in retrosplenial cortex; however, contrary to the unidirectional hypothesis, neocortical activation exhibited a continuum of activation timings relative to SWRs, varying from leading to lagging. Thus, contrary to the model in which SWRs arise spontaneously in the hippocampus, neocortical activation often precedes SWRs and may thus constitute a trigger event in which neocortical information seeds associative reactivation of hippocampal indices. This timing continuum is consistent with a dynamics in which older, more consolidated memories may in fact initiate the hippocampal-neocortical dialog, whereas reactivation of newer memories may be initiated predominantly in the hippocampus.

neuroscience↗