Editing Place cell (section)

==Background==

Place cells were first discovered by John O'Keefe and Jonathan Dostrovsky in 1971 in rats' hippocampuses.<ref name="O'Keefe-1971">{{Cite journal|last1=O'Keefe|first1=J.|last2=Dostrovsky|first2=J.|date=November 1971|title=The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat|journal=Brain Research|volume=34|issue=1|pages=171–175|doi=10.1016/0006-8993(71)90358-1|pmid=5124915|issn=0006-8993}}</ref><ref>{{Cite journal|last1=Abbott|first1=Alison|last2=Callaway|first2=Ewen|date=2014-10-09|title=Nobel prize for decoding brain's sense of place|journal=Nature News|language=en|volume=514|issue=7521|pages=153|doi=10.1038/514153a|pmid=25297415|bibcode=2014Natur.514..153A|doi-access=free}}</ref> They noticed that rats with impairments in their hippocampus performed poorly in spatial tasks, and thus hypothesised that this area must hold some kind of spatial representation of the environment. To test this hypothesis, they developed [[chronic electrode implant]]s, with which they could record the activity of individual cells [[extracellular]]ly in the hippocampus. They noted that some of the cells showed activity when a rat was "situated in a particular part of the testing platform facing in a particular direction".<ref name="O'Keefe-1971" /> These cells would later be called place cells.
[[File:Dynamics-of-place-boundary-and-object-encoding-in-rat-anterior-claustrum-Video 1.ogv|thumb|This video shows a rat running around in a circular environment (black line) and any time a particular cell is active (red dots). The red dots cluster around one location, which is the place field of the cell.]]
In 1976, O'Keefe performed a follow-up study, demonstrating the presence of what they called ''place units.''<ref name="O'Keefe-1976">{{Cite journal|last=O'Keefe|first=John|date=1976-01-01|title=Place units in the hippocampus of the freely moving rat|journal=Experimental Neurology|volume=51|issue=1|pages=78–109|doi=10.1016/0014-4886(76)90055-8|pmid=1261644|s2cid=1113367|issn=0014-4886}}</ref> These units were cells that fired in a particular place in the environment, the place field. They are described as having a low resting firing rate (<1&nbsp;Hz) when a rat is not in its place field, but a particularly high firing rate, which can be over 100&nbsp;Hz in some cases, within the place field.<ref>{{Cite journal|last1=Eichenbaum|first1=Howard|last2=Dudchenko|first2=Paul|last3=Wood|first3=Emma|last4=Shapiro|first4=Matthew|last5=Tanila|first5=Heikki|date=1999-06-01|title=The Hippocampus, Memory, and Place Cells: Is It Spatial Memory or a Memory Space?|journal=Neuron|language=en|volume=23|issue=2|pages=209–226|doi=10.1016/S0896-6273(00)80773-4|issn=0896-6273|pmid=10399928|s2cid=8518920|doi-access=free}}</ref> Additionally, O'Keefe described six special cells, which he called ''misplace units'', which also fire only in a particular place, but only when the rat performed an additional behaviour, such as sniffing, which was often correlated with the presence of a novel stimulus, or the absence of an expected stimulus.<ref name="O'Keefe-1976" /> The findings ultimately supported the cognitive map theory, the idea that the hippocampus hold a spatial representation, a [[cognitive map]] of the environment.<ref>{{cite journal|last=O'Keefe|first=John|author2=Nadel, Lynn|date=1 December 1979|title=The Hippocampus as a Cognitive Map|journal=Behavioral and Brain Sciences|volume=2|issue=4|pages=487–533|doi=10.1017/s0140525x00063949|s2cid=144038992 |id={{ProQuest|616519952}}}}</ref>

There has been much debate as to whether hippocampal place cells function depends on [[landmark]]s in the environment, on environmental boundaries, or on an interaction between the two.<ref>{{cite journal|last=Lew|first=Adena R.|title=Looking beyond the boundaries: Time to put landmarks back on the cognitive map?|journal=Psychological Bulletin|date=7 February 2011|volume=137|issue=3|pages=484–507|doi=10.1037/a0022315|pmid=21299273}}</ref> Additionally, not all place cells rely on the same external cues. One important distinction in cues is local and distal, where local cues appear in the immediate vicinity of a subject, whereas distal cues are far away, and act more like landmarks. Individual place cells have been shown to follow either or rely on both.<ref>{{Cite journal|last=Knierim|first=James J.|date=2002-07-15|title=Dynamic Interactions between Local Surface Cues, Distal Landmarks, and Intrinsic Circuitry in Hippocampal Place Cells|journal=Journal of Neuroscience|language=en|volume=22|issue=14|pages=6254–6264|doi=10.1523/JNEUROSCI.22-14-06254.2002|issn=0270-6474|pmid=12122084|pmc=6757929}}</ref><ref>{{Cite journal|last1=Etienne|first1=Ariane S.|last2=Jeffery|first2=Kathryn J.|date=2004|title=Path integration in mammals|journal=Hippocampus|language=en|volume=14|issue=2|pages=180–192|doi=10.1002/hipo.10173|issn=1098-1063|pmid=15098724|citeseerx=10.1.1.463.1315|s2cid=1646974}}</ref> Additionally, the cues on which the place cells rely may depend on previous experience of the subject and the saliency of the cue.<ref>{{Cite journal|last1=Bostock|first1=Elizabeth|last2=Muller|first2=Robert U.|last3=Kubie|first3=John L.|date=1991|title=Experience-dependent modifications of hippocampal place cell firing|journal=Hippocampus|language=en|volume=1|issue=2|pages=193–205|doi=10.1002/hipo.450010207|pmid=1669293|s2cid=31246290|issn=1098-1063}}</ref><ref name="Moser-2008" />

There has also been much debate as to whether hippocampal pyramidal cells truly encode non-spatial information as well as spatial information. According to the cognitive map theory, the hippocampus's primary role is to store spatial information through place cells and the hippocampus was biologically designed to provide a subject with spatial information.<ref name="okeefe1999">{{cite journal|last=O'Keefe|first=John|title=Do hippocampal pyramidal cells signal non-spatial as well as spatial information?|journal=Hippocampus|date=3 September 1999|volume=9|issue=4|pages=352–364|doi=10.1002/(SICI)1098-1063(1999)9:4<352::AID-HIPO3>3.0.CO;2-1|pmid=10495018|s2cid=1961703 }}</ref> Recent findings, such as a study showing that place cells respond to non-spatial dimensions, such as sound frequency, disagree with the cognitive map theory.<ref name="Aronov-2017">{{Cite journal|last1=Aronov|first1=Dmitriy|last2=Nevers|first2=Rhino|last3=Tank|first3=David W.|date=2017-03-29|title=Mapping of a non-spatial dimension by the hippocampal/entorhinal circuit|journal=Nature|volume=543|issue=7647|pages=719–722|doi=10.1038/nature21692|issn=0028-0836|pmc=5492514|pmid=28358077|bibcode=2017Natur.543..719A}}</ref> Instead, they support a new theory saying that the hippocampus has a more general function encoding continuous variables, and location just happens to be one of those variables.<ref name="Aronov-2017" /> This fits in with the idea that the hippocampus has a predictive function.<ref name="Stachenfeld-2017">{{Cite journal|last1=Stachenfeld|first1=Kimberly L.|last2=Botvinick|first2=Matthew M.|last3=Gershman|first3=Samuel J.|date=2017|title=The hippocampus as a predictive map|journal=Nature Neuroscience|language=en|volume=20|issue=11|pages=1643–1653|doi=10.1038/nn.4650|pmid=28967910|s2cid=205441266|issn=1546-1726|url=https://www.biorxiv.org/content/biorxiv/early/2017/07/27/097170.full.pdf}}</ref><ref>{{Cite journal|last1=Behrens|first1=Timothy E. J.|last2=Muller|first2=Timothy H.|last3=Whittington|first3=James C. R.|last4=Mark|first4=Shirley|last5=Baram|first5=Alon B.|last6=Stachenfeld|first6=Kimberly L.|last7=Kurth-Nelson|first7=Zeb|date=2018-10-24|title=What Is a Cognitive Map? Organizing Knowledge for Flexible Behavior|journal=Neuron|volume=100|issue=2|pages=490–509|doi=10.1016/j.neuron.2018.10.002|pmid=30359611|issn=0896-6273|doi-access=free}}</ref> 
[[File:RatGPS.svg|left|thumb|[[Grid cell]]s and place cells work together to determine the position of the animal]]

=== Relationship to grid cells ===
It has been proposed that place cells are derivatives of [[grid cell]]s, pyramidal cells in the entorhinal cortex. This theory suggests that the place fields of the place cells are a combination of several grid cells, which have hexagonal grid-like patterns of activity. The theory has been supported by computational models. The relation may arise through [[Hebbian theory|Hebbian learning]].<ref name="Moser-2008">{{Cite journal |last1=Moser |first1=Edvard I.|last2=Kropff |first2=Emilio |last3=Moser |first3=May-Britt |date=2008 |title=Place Cells, Grid Cells, and the Brain's Spatial Representation System |journal=Annual Review of Neuroscience |volume=31 |issue=1 |pages=69–89 |doi=10.1146/annurev.neuro.31.061307.090723|pmid=18284371 |s2cid=16036900}}</ref> But grid cells may perform a more supporting role in the formation of place fields, such as path integration input.<ref>{{Cite journal |last1=Bush |first1=Daniel |last2=Barry |first2=Caswell |last3=Burgess |first3=Neil |date=2014-03-01|title=What do grid cells contribute to place cell firing? |journal=Trends in Neurosciences |volume=37 |issue=3 |pages=136–145 |doi=10.1016/j.tins.2013.12.003 |pmid=24485517 |pmc=3945817 |issn=0166-2236}}</ref>
Another non-spatial explanation of hippocampal function suggests that the hippocampus performs clustering of inputs to produce representations of the current context – spatial or non-spatial.<ref>{{Cite journal |last1=Mok |first1=Robert M. |last2=Love |first2=Bradley C. |date=2019-12-12 |title=A non-spatial account of place and grid cells based on clustering models of concept learning |journal=Nature Communications |volume=10|issue=1|pages=5685 |doi=10.1038/s41467-019-13760-8 |pmid=31831749 |pmc=6908717 |bibcode=2019NatCo..10.5685M |issn=2041-1723}}</ref>

[[File:Hippocampus.gif|thumb|Place cells are found in the hippocampus, a structure in the medial temporal lobe of the brain.]]