THE MEDIAL ENTORHINAL CORTEX IS NECESSARY FOR TEMPORAL ORGANIZATION OF HIPPOCAMPAL NEURONAL ACTIVITY

The superficial layers of the medial entorhinal cortex (MEC) are a major input to the hippocampus. The high proportion of spatially modulated cells, including grid cells and border cells, in these layers suggests that MEC inputs are critical for the representation of space in the hippocampus. However, selective manipulations of the MEC do not completely abolish hippocampal spatial firing. To determine whether other hippocampal firing characteristics depend more critically on MEC inputs, we recorded from hippocampal CA1 cells in rats with MEC lesions. Theta phase precession was substantially disrupted, even during periods of stable spatial firing. Our findings indicate that MEC inputs to the hippocampus are required for the temporal organization of hippocampal firing patterns and suggest that cognitive functions that depend on precise neuronal sequences in the hippocampal theta cycle are particularly dependent on the MEC.

• Publication year

  2015

• Venue

  Nature Neuroscience

• Publication date

  2015-06-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/nn.4056PMID 26120964PMCID 4711275
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Dissociation between the Experience-Dependent Development of Hippocampal Theta Sequences and Single-Trial Phase Precession

  2015cited by this paper
• New and distinct hippocampal place codes are generated in a new environment during septal inactivation.

  2014cited by this paper
• Modeling Inheritance of Phase Precession in the Hippocampal Formation

  2014cited by this paper
• Theta sequences are essential for internally generated hippocampal firing fields

  2014cited by this paper
• Medial entorhinal cortex lesions only partially disrupt hippocampal place cells and hippocampus-dependent place memory.

  2014cited by this paper
• Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality

  2014cited by this paper
• Hippocampal activation during the recall of remote spatial memories in radial maze tasks.

  2013cited by this paper
• Optogenetic Dissection of Entorhinal-Hippocampal Functional Connectivity

  2013cited by this paper
• Segmentation of spatial experience by hippocampal theta sequences

  2012cited by this paper
• Quantifying circular-linear associations: hippocampal phase precession.

  2012cited by this paper
• Hippocampal Phase Precession from Dual Input Components

  2012cited by this paper
• A Model of Intracellular Theta Phase Precession Dependent on Intrinsic Subthreshold Membrane Currents

  2011cited by this paper
• Reduction of Theta Rhythm Dissociates Grid Cell Spatial Periodicity from Directional Tuning

  2011cited by this paper
• Learning a Sparse Code for Temporal Sequences Using STDP and Sequence Compression

  2011cited by this paper
• The Spatial Periodicity of Grid Cells Is Not Sustained During Reduced Theta Oscillations

  2011cited by this paper
• Chronux: a platform for analyzing neural signals.

  2010cited by this paper
• Theta modulation in the medial and the lateral entorhinal cortices.

  2010cited by this paper
• Alteration of Theta Timescale Dynamics of Hippocampal Place Cells by a Cannabinoid Is Associated with Memory Impairment

  2009cited by this paper
• Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop.

  2009cited by this paper
• Intracellular dynamics of hippocampal place cells during virtual navigation

  2009cited by this paper
• Phase Precession Through Synaptic Facilitation

  2008cited by this paper
• Representation of Geometric Borders in the Entorhinal Cortex

  2008cited by this paper
• Theta phase–specific codes for two-dimensional position, trajectory and heading in the hippocampus

  2008cited by this paper
• Unstable CA1 place cell representation in rats with entorhinal cortex lesions

  2008cited by this paper
• Hippocampus-independent phase precession in entorhinal grid cells

  2008cited by this paper
• Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex

  2006cited by this paper
• Organization of hippocampal cell assemblies based on theta phase precession

  2006cited by this paper
• Temporal encoding of place sequences by hippocampal cell assemblies.

  2006cited by this paper
• Quantitative measures of cluster quality for use in extracellular recordings.

  2005cited by this paper
• Complementary Roles of Cholecystokinin- and Parvalbumin-Expressing GABAergic Neurons in Hippocampal Network Oscillations

  2005cited by this paper
• A test of the reverberatory activity hypothesis for hippocampal 'place' cells.

  2005cited by this paper
• Microstructure of a spatial map in the entorhinal cortex

  2005cited by this paper
• UANTITATIVE MEASURES OF CLUSTER QUALITY FOR USE IN XTRACELLULAR RECORDINGS

  2005cited by this paper
• Spike phase precession persists after transient intrahippocampal perturbation

  2005cited by this paper
• Major Dissociation Between Medial and Lateral Entorhinal Input to Dorsal Hippocampus

  2005cited by this paper
• Coding and learning of behavioral sequences.

  2004cited by this paper
• Independent rate and temporal coding in hippocampal pyramidal cells

  2003cited by this paper
• Dynamically detuned oscillations account for the coupled rate and temporal code of place cell firing

  2003cited by this paper
• Spike train dynamics predicts theta-related phase precession in hippocampal pyramidal cells

  2002cited by this paper
• A Proposed Function for Hippocampal Theta Rhythm: Separate Phases of Encoding and Retrieval Enhance Reversal of Prior Learning

  2002cited by this paper
• Role of experience and oscillations in transforming a rate code into a temporal code

  2002cited by this paper
• Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells.

  2001cited by this paper
• Neuronal Dynamics of Predictive Coding

  2001cited by this paper
• Synaptic modification by correlated activity: Hebb's postulate revisited.

  2001cited by this paper
• NMDA receptor antagonism blocks experience-dependent expansion of hippocampal "place fields".

  2001cited by this paper
• Dendritic mechanisms of phase precession in hippocampal CA1 pyramidal neurons.

  2001cited by this paper
• Topics in Circular Statistics

  2001cited by this paper
• Theta oscillations in somata and dendrites of hippocampal pyramidal cells in vivo: Activity‐dependent phase‐precession of action potentials

  1998cited by this paper
• Population dynamics and theta rhythm phase precession of hippocampal place cell firing: A spiking neuron model

  1998cited by this paper
• Hippocampal CA3 region predicts memory sequences: accounting for the phase precession of place cells.

  1996cited by this paper
• Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences

  1996cited by this paper
• Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells

  1995cited by this paper
• Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat.

  1995cited by this paper
• Phase relationship between hippocampal place units and the EEG theta rhythm

  1993cited by this paper
• An Information-Theoretic Approach to Deciphering the Hippocampal Code

  1992cited by this paper
• The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells

  1992cited by this paper
• Spatial correlates of hippocampal unit activity are altered by lesions of the fornix and endorhinal cortex.

  1980cited by this paper

• Dynamical modulation of hippocampal replay through firing rate adaptation

  2026cites this paper
• Decoding medial entorhinal cortical dynamics produces planning-like alternations in hippocampal theta sequences

  2026cites this paper
• Medial entorhinal-hippocampal desynchronization parallels the emergence of memory impairment in a mouse model of Alzheimer’s disease pathology

  2025cites this paper
• The impact of Vav1 on epileptogenesis and neuronal apoptosis: insights from Sirt1 activation.

  2025cites this paper
• Auditory regulation of hippocampal locomotion circuits by a non-canonical reticular-limbic pathway

  2025cites this paper
• Emergence of Spatial Representation in an Actor-Critic Agent with Hippocampus-Inspired Sequence Generator

  2025cites this paper
• Medial septum-dependent encoding of contextual inputs by hippocampal splitter cells.

  2025cites this paper
• tACS induces state-dependent shifts in inhibitory phase preference consistent with phase precession

  2025cites this paper
• Synaptic histamine shapes the neurocomputational dynamics of human learning

  2025cites this paper
• The Neurobiology of Learning and Memory in Rodent Models of Fetal Alcohol Spectrum Disorders.

  2025cites this paper
• Retrosplenial inputs drive visual representations in the medial entorhinal cortex

  2024cites this paper
• Binding in hippocampal-entorhinal circuits enables compositionality in cognitive maps

  2024cites this paper
• Modeling the contribution of theta-gamma coupling to sequential memory, imagination, and dreaming

  2024cites this paper
• Remapping revisited: how the hippocampus represents different spaces

  2024cites this paper
• Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models

  2024cites this paper
• The generative neural microdynamics of cognitive processing.

  2024cites this paper
• Grid cells: the missing link in understanding Parkinson’s disease?

  2024cites this paper
• Contextual memory engrams, and the neuromodulatory influence of the locus coeruleus

  2024cites this paper
• A population code for idiothetic representations in the hippocampal-septal circuit

  2024cites this paper
• Low rate hippocampal delay period activity encodes behavioral experience

  2024cites this paper
• Binding in hippocampal-entorhinal circuits enables compositionality in cognitive maps

  2024cites this paper
• Idiothetic representations are modulated by availability of sensory inputs and task demands in the hippocampal-septal circuit.

  2024cites this paper
• Dynamical Modulation of Hippocampal Replay Sequences through Firing Rate Adaptation

  2024cites this paper
• Theta phase precession supports memory formation and retrieval of naturalistic experience in humans

  2024cites this paper
• Task-anchored grid cell firing is selectively associated with successful path integration-dependent behaviour

  2024cites this paper
• Optogenetic silencing of medial septal GABAergic neurons disrupts grid cell spatial and temporal coding in the medial entorhinal cortex.

  2024cites this paper
• Predictive grid coding in the medial entorhinal cortex

  2024cites this paper
• Environmental enrichment reduces restricted repetitive behavior by altering gray matter microstructure

  2024cites this paper
• Title: Hippocampal replay facilitates the formation of entorhinal grid cells

  2023cites this paper
• Low Rate Hippocampal Delay Period Activity Encodes Behavioral Experience

  2023cites this paper
• Associative and predictive hippocampal codes support memory-guided behaviors

  2023cites this paper
• Retrosplenial inputs drive diverse visual representations in the medial entorhinal cortex

  2023cites this paper
• Local activation of CA1 pyramidal cells induces theta phase precession

  2023cites this paper
• Hippocampal orchestration of associative and sequential memory networks for episodic retrieval.

  2023cites this paper
• Uncorrelated bilateral cortical input becomes timed across hippocampal subfields for long waves whereas gamma waves are largely ipsilateral

  2023cites this paper
• Septo-hippocampal dynamics and the encoding of space and time.

  2023cites this paper
• Effects of theta phase precessing optogenetic intervention on hippocampal neuronal reactivation and spatial maps

  2023cites this paper
• [Neural bases of memory and spatial navigation].

  2023cites this paper
• Postnatal Maturation of Membrane Potential Dynamics during in Vivo Hippocampal Ripples

  2023cites this paper
• Phase-locking of hippocampal CA3 neurons to distal CA1 theta oscillations selectively predicts memory performance

  2023cites this paper
• Hippocampal Theta Phase Precession Supports Memory Formation and Retrieval of Naturalistic Experience in Humans

  2023cites this paper
• Theta phase precession at encoding predicts subsequent memory of sensory-driven vector fields, & occurs in memory-dependent fields at retrieval

  2023cites this paper
• Direct entorhinal control of CA1 temporal coding

  2023cites this paper
• CA3 circuit model compressing sequential information in theta oscillation and replay

  2023cites this paper
• Episodic Memory formation: A review of complex Hippocampus input pathways.

  2023cites this paper
• Theta oscillations represent collective dynamics of multineuronal membrane potentials of murine hippocampal pyramidal cells

  2023cites this paper
• Postnatal maturation of in vivo membrane potential dynamics during hippocampal ripples

  2023cites this paper
• Distinct spatial maps and multiple object codes in the lateral entorhinal cortex

  2023cites this paper
• Mechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures

  2022cites this paper
• Cholinergic Regulation of Hippocampal Theta Rhythm

  2022cites this paper
• Subicular neurons represent multiple variables of a hippocampal-dependent task by using theta rhythm

  2022cites this paper
• Compositional Sequence Generation in the Entorhinal–Hippocampal System

  2022influential citation
• The medial entorhinal cortex is necessary for the stimulus control over hippocampal place fields by distal, but not proximal, landmarks

  2022cites this paper
• Neurogliaform cells dynamically decouple neuronal synchrony between brain areas

  2022cites this paper
• Distinct roles of dentate gyrus and medial entorhinal cortex inputs for phase precession and temporal correlations in the hippocampal CA3 area

  2022cites this paper
• Skipping ahead: A circuit for representing the past, present, and future

  2021cites this paper
• The hippocampus converts dynamic entorhinal inputs into stable spatial maps

  2021cites this paper
• Experience-dependent changes in hippocampal spatial activity and hippocampal circuit function are disrupted in a rat model of Fragile X Syndrome

  2021cites this paper
• Medial entorhinal cortex lesions produce delay-dependent disruptions in memory for elapsed time.

  2021cites this paper
• The grid code for ordered experience

  2021cites this paper
• Orthogonal representation of task-related information in theta phase-based multiple place fields of single units in the subiculum

  2021cites this paper
• Burst activity plays no role in the field‐to‐field variability and rate remapping of grid cells

  2021cites this paper
• Learning Spatiotemporal Properties of Hippocampal Place Cells

  2021influential citation
• Learning an Efficient Hippocampal Place Map from Entorhinal Inputs Using Non-Negative Sparse Coding

  2021cites this paper
• A Time Duration Discrimination Task for the Study of Elapsed Time Processing in Rats.

  2021cites this paper
• Flexible modulation of sequence generation in the entorhinal-hippocampal system

  2021cites this paper
• Two septal-entorhinal GABAergic projections differentially control coding properties of spatially tuned neurons in the medial entorhinal cortex.

  2021cites this paper
• Distinct hippocampal network states support theta phase precession and theta sequences in CA1

  2021cites this paper
• Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies

  2021cites this paper
• A role for medial entorhinal cortex in spatial and nonspatial forms of memory in rats.

  2021cites this paper
• Relevance of a Novel Circuit-Level Model of Episodic Memories to Alzheimer’s Disease

  2021cites this paper
• Dentate Gyrus and CA3 GABAergic Interneurons Bidirectionally Modulate Signatures of Internal and External Drive to CA1

  2021cites this paper
• Directional Tuning of Phase Precession Properties in the Hippocampus

  2021cites this paper
• Extrinsic control and intrinsic computation in the hippocampal CA1 circuit.

  2021influential citation
• Medial Entorhinal Cortex Excitatory Neurons Are Necessary for Accurate Timing

  2021cites this paper
• Episodic Memories: How do the Hippocampus and the Entorhinal Ring Attractors Cooperate to Create Them?

  2020cites this paper
• Update on temporal lobe‐dependent information processing, in health and disease

  2020influential citation
• Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

  2020cites this paper
• Burst activity plays no role for the field-to-field variability and rate remapping of grid cells

  2020cites this paper
• Subcircuits of deep and superficial CA1 place cells support efficient spatial coding across heterogeneous environments

  2020cites this paper
• Disrupted Spatial Maps in Epilepsy Highlight the Importance of Timing in Neural Codes

  2020cites this paper
• Cell assemblies, sequences and temporal coding in the hippocampus.

  2020cites this paper
• Neuronal Oscillations of Wakefulness and Sleep: Windows on Spontaneous Activity of the Brain

  2020cites this paper
• Theta Rhythm in Hippocampus and Cognition

  2020cites this paper
• Tipping the Scales: Peptide-Dependent Dysregulation of Neural Circuit Dynamics in Alzheimer's Disease.

  2020cites this paper
• Learning an efficient place cell map from grid cells using non-negative sparse coding

  2020cites this paper
• Spatial Navigation.

  2020cites this paper
• Neural Circuits of Innate Behaviors

  2020cites this paper
• Phase precession in the human hippocampus and entorhinal cortex

  2020cites this paper
• Time as the fourth dimension in the hippocampus.

  2020cites this paper
• A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease

  2020cites this paper
• Medial entorhinal cortex lesions induce degradation of CA1 place cell firing stability when self-motion information is used

  2020cites this paper
• Spatial Information Encoding across Multiple Neocortical Regions Depends on an Intact Hippocampus

  2020cites this paper
• Hippocampal spike-time correlations and place-field overlaps during open field foraging

  2019cites this paper
• Spatiotemporally random and diverse grid cell spike patterns contribute to the transformation of grid cell to place cell in a neural network model

  2019cites this paper
• Time Cells in the Hippocampus Are Neither Dependent on Medial Entorhinal Cortex Inputs nor Necessary for Spatial Working Memory.

  2019influential citation
• The Integration of Goal-Directed Signals onto Spatial Maps of Hippocampal Place Cells.

  2019cites this paper
• Modality‐specific Subpopulations of Place Fields Coexist in the Hippocampus

  2019cites this paper
• Hippocampal Sequences During Exploration: Mechanisms and Functions

  2019cites this paper
• Functional Connectivity between Hippocampus and Lateral Septum is Affected in Very Young Alzheimer's Transgenic Mouse Model.

  2019cites this paper