Hippocampal Neurons Represent Events As Transferable Units of Experience

Overview

Journal Nat Neurosci

Date 2020 Apr 7

PMID 32251386

Citations 46

Authors

Chen Sun

Wannan Yang

Jared Martin

Susumu Tonegawa

Affiliations

Soon will be listed here.

Abstract

The brain codes continuous spatial, temporal and sensory changes in daily experience. Recent studies suggest that the brain also tracks experience as segmented subdivisions (events), but the neural basis for encoding events remains unclear. Here, we designed a maze for mice, composed of four materially indistinguishable lap events, and identify hippocampal CA1 neurons whose activity are modulated not only by spatial location but also lap number. These 'event-specific rate remapping' (ESR) cells remain lap-specific even when the maze length is unpredictably altered within trials, which suggests that ESR cells treat lap events as fundamental units. The activity pattern of ESR cells is reused to represent lap events when the maze geometry is altered from square to circle, which suggests that it helps transfer knowledge between experiences. ESR activity is separately manipulable from spatial activity, and may therefore constitute an independent hippocampal code: an 'event code' dedicated to organizing experience by events as discrete and transferable units.

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References

Pastalkova E, Itskov V, Amarasingham A, Buzsaki G . Internally generated cell assembly sequences in the rat hippocampus. Science. 2008; 321(5894):1322-7. PMC: 2570043. DOI: 10.1126/science.1159775. View

Behrens T, Muller T, Whittington J, Mark S, Baram A, Stachenfeld K . What Is a Cognitive Map? Organizing Knowledge for Flexible Behavior. Neuron. 2018; 100(2):490-509. DOI: 10.1016/j.neuron.2018.10.002. View

Czurko A, Hirase H, Csicsvari J, Buzsaki G . Sustained activation of hippocampal pyramidal cells by 'space clamping' in a running wheel. Eur J Neurosci. 1999; 11(1):344-52. DOI: 10.1046/j.1460-9568.1999.00446.x. View

Foster D, Wilson M . Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature. 2006; 440(7084):680-3. DOI: 10.1038/nature04587. View

Whittington J, Muller T, Mark S, Chen G, Barry C, Burgess N . The Tolman-Eichenbaum Machine: Unifying Space and Relational Memory through Generalization in the Hippocampal Formation. Cell. 2020; 183(5):1249-1263.e23. PMC: 7707106. DOI: 10.1016/j.cell.2020.10.024. View

Chen T, Wardill T, Sun Y, Pulver S, Renninger S, Baohan A . Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature. 2013; 499(7458):295-300. PMC: 3777791. DOI: 10.1038/nature12354. View

McNaughton B, Barnes C, Okeefe J . The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp Brain Res. 1983; 52(1):41-9. DOI: 10.1007/BF00237147. View

Tsao A, Sugar J, Lu L, Wang C, Knierim J, Moser M . Integrating time from experience in the lateral entorhinal cortex. Nature. 2018; 561(7721):57-62. DOI: 10.1038/s41586-018-0459-6. View

Hard B, Tversky B, Lang D . Making sense of abstract events: building event schemas. Mem Cognit. 2007; 34(6):1221-35. DOI: 10.3758/bf03193267. View

10.

Bulkin D, Sinclair D, Law L, Smith D . Hippocampal state transitions at the boundaries between trial epochs. Hippocampus. 2019; 30(6):582-595. PMC: 11127720. DOI: 10.1002/hipo.23180. View

11.

Sakurai Y . Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat. Neuroscience. 2002; 115(4):1153-63. DOI: 10.1016/s0306-4522(02)00509-2. View

12.

Derdikman D, Whitlock J, Tsao A, Fyhn M, Hafting T, Moser M . Fragmentation of grid cell maps in a multicompartment environment. Nat Neurosci. 2009; 12(10):1325-32. DOI: 10.1038/nn.2396. View

13.

Wood E, Dudchenko P, Eichenbaum H . The global record of memory in hippocampal neuronal activity. Nature. 1999; 397(6720):613-6. DOI: 10.1038/17605. View

14.

Leutgeb S, Ragozzino K, Mizumori S . Convergence of head direction and place information in the CA1 region of hippocampus. Neuroscience. 2000; 100(1):11-9. DOI: 10.1016/s0306-4522(00)00258-x. View

15.

Leutgeb S, Leutgeb J, Barnes C, Moser E, McNaughton B, Moser M . Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science. 2005; 309(5734):619-23. DOI: 10.1126/science.1114037. View

16.

Robinson N, Priestley J, Rueckemann J, Garcia A, Smeglin V, Marino F . Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons. Neuron. 2017; 94(3):677-688.e6. PMC: 5465388. DOI: 10.1016/j.neuron.2017.04.003. View

17.

Gauthier J, Tank D . A Dedicated Population for Reward Coding in the Hippocampus. Neuron. 2018; 99(1):179-193.e7. PMC: 7023678. DOI: 10.1016/j.neuron.2018.06.008. View

18.

Grieves R, Jenkins B, Harland B, Wood E, Dudchenko P . Place field repetition and spatial learning in a multicompartment environment. Hippocampus. 2015; 26(1):118-34. PMC: 4745022. DOI: 10.1002/hipo.22496. View

19.

Singer A, Karlsson M, Nathe A, Carr M, Frank L . Experience-dependent development of coordinated hippocampal spatial activity representing the similarity of related locations. J Neurosci. 2010; 30(35):11586-604. PMC: 2966971. DOI: 10.1523/JNEUROSCI.0926-10.2010. View

20.

Mukamel E, Nimmerjahn A, Schnitzer M . Automated analysis of cellular signals from large-scale calcium imaging data. Neuron. 2009; 63(6):747-60. PMC: 3282191. DOI: 10.1016/j.neuron.2009.08.009. View