Integrating time from experience in the lateral entorhinal cortex

The encoding of time and its binding to events are crucial for episodic memory, but how these processes are carried out in hippocampal–entorhinal circuits is unclear. Here we show in freely foraging rats that temporal information is robustly encoded across time scales from seconds to hours within the overall population state of the lateral entorhinal cortex. Similarly pronounced encoding of time was not present in the medial entorhinal cortex or in hippocampal areas CA3–CA1. When animals’ experiences were constrained by behavioural tasks to become similar across repeated trials, the encoding of temporal flow across trials was reduced, whereas the encoding of time relative to the start of trials was improved. The findings suggest that populations of lateral entorhinal cortex neurons represent time inherently through the encoding of experience. This representation of episodic time may be integrated with spatial inputs from the medial entorhinal cortex in the hippocampus, allowing the hippocampus to store a unified representation of what, where and when.Temporal information that is useful for episodic memory is encoded across a wide range of timescales in the lateral entorhinal cortex, arising inherently from its representation of ongoing experience.

[1]  A. Nobre,et al.  Time in Cortical Circuits , 2015, The Journal of Neuroscience.

[2]  O. Sporns,et al.  Architecture of the cerebral cortical association connectome underlying cognition , 2015, Proceedings of the National Academy of Sciences.

[3]  Marc W. Howard,et al.  A distributed representation of temporal context , 2002 .

[4]  H. Eichenbaum.  On the Integration of Space, Time, and Memory , 2017, Neuron.

[5]  W. Maass,et al.  State-dependent computations: spatiotemporal processing in cortical networks , 2009, Nature Reviews Neuroscience.

[6]  Chih-Jen Lin,et al.  LIBLINEAR: A Library for Large Linear Classification , 2008, J. Mach. Learn. Res..

[7]  Lacey J. Kitch,et al.  Long-term dynamics of CA1 hippocampal place codes , 2013, Nature Neuroscience.

[8]  Sachin S. Deshmukh,et al.  Representation of Non-Spatial and Spatial Information in the Lateral Entorhinal Cortex , 2011, Front. Behav. Neurosci..

[9]  Li Lu,et al.  Coordination of entorhinal–hippocampal ensemble activity during associative learning , 2014, Nature.

[10]  Matthias J. Gruber,et al.  Hippocampal Activity Patterns Carry Information about Objects in Temporal Context , 2014, Neuron.

[11]  György Buzsáki,et al.  Space and time in the brain , 2017, Science.

[12]  Lila Davachi,et al.  Similarity Breeds Proximity: Pattern Similarity within and across Contexts Is Related to Later Mnemonic Judgments of Temporal Proximity , 2014, Neuron.

[13]  John T Wixted,et al.  Learning and remembering real-world events after medial temporal lobe damage , 2016, Proceedings of the National Academy of Sciences.

[14]  Qian Du,et al.  A Unified Mathematical Framework for Coding Time, Space, and Sequences in the Hippocampal Region , 2014, The Journal of Neuroscience.

[15]  Hugo Merchant,et al.  Neural basis of the perception and estimation of time. , 2013, Annual review of neuroscience.

[16]  D. Buonomano,et al.  The neural basis of temporal processing. , 2004, Annual review of neuroscience.

[17]  J. Knierim,et al.  Major Dissociation Between Medial and Lateral Entorhinal Input to Dorsal Hippocampus , 2005, Science.

[18]  Carol A Barnes,et al.  Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex , 2013, Nature Neuroscience.

[19]  Alcino J. Silva,et al.  A shared neural ensemble links distinct contextual memories encoded close in time , 2016, Nature.

[20]  Mark P. Brandon,et al.  During Running in Place, Grid Cells Integrate Elapsed Time and Distance Run , 2015, Neuron.

[21]  Marc W Howard,et al.  Gradual Changes in Hippocampal Activity Support Remembering the Order of Events , 2007, Neuron.

[22]  Charu C. Aggarwal,et al.  On the Surprising Behavior of Distance Metrics in High Dimensional Spaces , 2001, ICDT.

[23]  Marc W Howard,et al.  The Same Hippocampal CA1 Population Simultaneously Codes Temporal Information over Multiple Timescales , 2018, Current Biology.

[24]  M. Witter,et al.  A Specific Role of the Human Hippocampus in Recall of Temporal Sequences , 2009, The Journal of Neuroscience.

[25]  H. Eichenbaum,et al.  Critical role of the hippocampus in memory for sequences of events , 2002, Nature Neuroscience.

[26]  H. Eichenbaum.  Time cells in the hippocampus: a new dimension for mapping memories , 2014, Nature Reviews Neuroscience.

[27]  M. Moser,et al.  Traces of Experience in the Lateral Entorhinal Cortex , 2013, Current Biology.

[28]  Paul E. Gilbert,et al.  The role of the hippocampus in memory for the temporal order of a sequence of odors. , 2002, Behavioral neuroscience.

[29]  Y. Naya,et al.  Integrating What and When Across the Primate Medial Temporal Lobe , 2011, Science.

[30]  Yasser Roudi,et al.  Ten Years of Grid Cells. , 2016, Annual review of neuroscience.

[31]  Fraser T. Sparks,et al.  Hippocampal CA2 Activity Patterns Change over Time to a Larger Extent than between Spatial Contexts , 2015, Neuron.

[32]  Kaori Takehara-Nishiuchi,et al.  Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex , 2017, eLife.

[33]  D. Hassabis,et al.  Deconstructing episodic memory with construction , 2007, Trends in Cognitive Sciences.

[34]  Arne D. Ekstrom,et al.  Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain. , 2007, Learning & memory.

[35]  D. Durstewitz,et al.  Contextual encoding by ensembles of medial prefrontal cortex neurons , 2012, Proceedings of the National Academy of Sciences.

[36]  M. Shapiro,et al.  Episodic memory—From brain to mind , 2006, Hippocampus.

[37]  H. Eichenbaum,et al.  Hippocampal “Time Cells” Bridge the Gap in Memory for Discontiguous Events , 2011, Neuron.

[38]  Marc W Howard,et al.  Human Episodic Memory Retrieval Is Accompanied by a Neural Contiguity Effect , 2018, The Journal of Neuroscience.

[39]  Ann M Graybiel,et al.  Neural representation of time in cortico-basal ganglia circuits , 2009, Proceedings of the National Academy of Sciences.

[40]  Edvard I. Moser,et al.  Speed cells in the medial entorhinal cortex , 2015, Nature.

[41]  Xiao-Jing Wang,et al.  The importance of mixed selectivity in complex cognitive tasks , 2013, Nature.

[42]  H. Eichenbaum,et al.  Complementary Functional Organization of Neuronal Activity Patterns in the Perirhinal, Lateral Entorhinal, and Medial Entorhinal Cortices , 2016, The Journal of Neuroscience.

[43]  Fraser T. Sparks,et al.  Neuronal code for extended time in the hippocampus , 2012, Proceedings of the National Academy of Sciences.

[44]  J. Disterhoft,et al.  Single Neurons in CA1 Hippocampus Encode Trace Interval Duration during Trace Heart Rate (Fear) Conditioning in Rabbit , 2003, The Journal of Neuroscience.

[45]  H. Eichenbaum,et al.  Hippocampal Neurons Encode Information about Different Types of Memory Episodes Occurring in the Same Location , 2000, Neuron.

[46]  Edvard I Moser,et al.  Development of the Spatial Representation System in the Rat , 2010, Science.

[47]  Li Lu,et al.  Topography of Place Maps along the CA3-to-CA2 Axis of the Hippocampus , 2015, Neuron.

[48]  A. Dickinson,et al.  Episodic-like memory during cache recovery by scrub jays , 1998, Nature.

[49]  Asohan Amarasingham,et al.  Internally Generated Cell Assembly Sequences in the Rat Hippocampus , 2008, Science.

[50]  D. Amaral,et al.  Entorhinal cortex of the rat: Organization of intrinsic connections , 1998, The Journal of comparative neurology.

[51]  Yaniv Ziv,et al.  Hippocampal ensemble dynamics timestamp events in long-term memory , 2015, eLife.