master gland
Fundamental Neuroscience
Jakobović AT. Place cells. pp. 73 – 78
place cells
Antun Tonko Jakobović
University of Zagreb, School of Medicine
0000-0003-0041-4054
Abstract
Place cells are pyramidal neurons in hippocampal CA1 and CA3 subfields. They emit bursts of signal at a particular location
in space — a place field. Some cells have multiple fields in large areas. Each cell covers one unit of a given environment. It
allows them to form a mental map of space. This approach is called a cognitive map theory. In different circumstances, firing
fields change. These alterations can be noticed in various experiments. There are two types of inputs that determine field
patterns. Metric inputs rely on vision and motion cues, while non-metric (contextual) inputs involve color, odor, rewards
etc. Contextual inputs decide which metric inputs will be used. These two interact in entorhinal cortex (EC). Main spatially
modulated cells in EC are grid cells. Others are head direction cells and border cells situated in different cortical areas. All
contribute to map formation. This map can be used for working memory or stored for future use. In some cases, these
functions can be disrupted. Acute and chronic ethanol uptake reduces cell’s electric activity. In Alzheimer’s disease, field
stability and spatial memory are affected. Nevertheless, aging, a normal physiological process, shares similar interference.
keywords: hippocampus, place cell, place field, spatial memory, remapping
INTRODUCTION
Place cells are complex-spike pyramidal neurons that emit
a series of signals within a specific location in space.1 This
restricted location in an environment is called a place field.
Each place cell usually has a single place field. With thousands of place cells covering each part of the available space,
they form a dynamic network that acts as a mental map of
the environment. This approach is called a cognitive map
theory. Thereby, place cells provide us with a sense of spatial awareness and a spatial context for memory formation.
First studies of hippocampal place cells started with O’Keefe
and Dostrovsky in 1971. They used miniature electrodes
for extracellular single-cell recording.2 Method is used to
correlate neural activity with rat’s location in space. Combining the periods of action potentials (neuron firings) and
camera-acquired position, a firing-rate map for a neuron can
be generated (Figure 1).
Figure 1.
Left — a recording set up. Right — firing-rate map for a place cell. It
ranges from yellow (no firing) to purple (high firing-rate). Observed
neuron (place cell) emits most signals at one specific location in a
test box. It is an upper-left sector.
Source: Place Cells, Remapping and Memory.
http://blog.brainfacts.org/2013/10/place-cells-remapping-and-memory/#.WIVjl33Areo. Published October 5, 2013.
Updated October 7, 2013. Accessed March 9, 2016.
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Since then, experimental methods have advanced. In 2014,
O’Keefe was awarded with The Nobel Prize in Physiology
or Medicine for his discovery of place cells. The other half
was awarded to M. B. Moser and E. Moser for their pioneer
research in grid cells. This article will sum up the most important findings to illustrate the place cell concept.
PLACE FIELDS
Place cells are distributed in CA1 and CA3 subfields of the
hippocampus. Although pyramidal neurons measure most
of the activity, some granule cells in dentate gyrus contribute as well. Firing bursts in place cells are observed during
translational movement. Place field (specific location where
cell bursts are recorded) shows an increase in size towards
the ventral pole of an imaginary dorso-ventral axis in which
neurons are arranged inside hippocampus. Therefore, different cells can measure unequal place fields depending
on their dorso-ventral position in hippocampal subfields.
This can be observed with an animal roaming around a small
platform. Firstly, towards the end of an environment, firing
fields get smaller. In contrast, central firing fields are larger
in size. Changes in size of the two-dimensional firing field are
independent in X and Y axis. In other words, firing field has
a surface determined by the X and Y coordinates. Theoretically, size variable in X axis changes while Y axis dimension
remains the same, and vice versa. Secondly, neighbouring
place fields do not necessarily imply adjacent neighbouring place cells. Surrounding neurons are likely to encode
nearby fields as much as the distant ones. It is opposite to
the organization of visual cortex. Despite nontopographical
mapping, a cell or group of cells active in a specific area is
unique. This means that certain cells will be emitting bursts
of signals at one position and others at other. Some neurons
January 2017 | Gyrus | Vol. 4 | No. 1
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Fundamental Neuroscience
Jakobović AT. Place cells. pp. 73 – 78
Figure 2.
Single-cell recording in differently shaped environments (cylinder
and rectangle). A scramble of firing fields can be noticed. Cue card
was not relocated.
Source: Place Cells, Remapping and Memory. http://blog.brainfacts.
org/2013/10/place-cells-remapping-and-memory/#.WIVjl33Areo.
Published October 5, 2013. Updated October 7, 2013. Accessed March 10, 2016.
would have identical or almost identical (“overlapping”) firing fields while the rest would have non-overlapping fields
in a given space. When animal changes environment, spatial
firing of hippocampal place cells alters. In other words, pair
of cells can have overlapping firing fields in one place, and
non-overlapping in other. This has drawn two conclusions.3
First, if a cell is active in both environments, one field cannot
predict location of the other field. In other words, certain
field is part of a particular environment. If a neuron triggers
at place Q in environment A and the same neuron triggers
at place Y in environment B, there is no correlation between
place Q and Y based only on the neural activity. Second, if a
cell is active in one environment, it doesn’t mean it’s active
in another one. This phenomenon is known as hippocampal
remapping. Several experiments should be mentioned. Figure 2 involves single-cell recording in two environments of
different shapes. Place fields are unpredictably scrambled
between two diverse boxes. This relates with Figure 3 where
two place cells with overlapping fields in circular space have
non-overlapping fields in triangular area. But how does one
know if a cell’s firing field is actually a place field? If a firing
field rotates following environmental rotation, than this field
is called a place field. Figure 4 depicts a place field rotation
accompanied by cue, the arc-shaped card, shift. Hence if a
cue determines neural activity of place cells, than removal of
cues includes change in that activity. This can be examined
within a closed box with multiple cues. One or more cue cards
can be removed. Removal of all cards (global remapping)
results in total diffuse disruption of activity. But a single-cue
removal (rate remapping) doesn’t considerably disrupt unit
fields. However, it does have impact on two factors. Place
Figure 3.
Single-cell recording in differently shaped environments (cylinder and triangle). Two separate cells in cylinder (session 1) have overlaping firing fields. Both cells in triangular box express non-overlaping place fields (session 2). Location of session 2 fields based on session
1 pattern cannot be predicted.
Source: Place Cells, Remapping and Memory. http://blog.brainfacts.org/2013/10/place-cells-remapping-and-memory/#.WIVjl33Areo.
Published October 5, 2013. Updated October 7, 2013. Accessed March 10, 2016.
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Jakobović AT. Place cells. pp. 73 – 78
INPUTS
Sensory information help place cells to encode location-specific firing. There are metric and contextual (i.e. non-metric)
inputs.5 Metric inputs provide information about distance and
direction. These can be in a linear or angular dimension and
involve visual and motion cues (e.g. touch and proprioception). They are mutually replaceable (isomorphic) as they
are metrically analogous. Non-metric inputs provide context
of a space in which an animal is located. This heterogeneous
non-metric group involves two subdivisions. So called stable
attributes, such as color, help to define environment just as it
is in time and space. Other ones are much more discrete and
involve odor, reward, shock and other conditioned stimuli.
We can think of both groups of non-metric stimuli as context
providers. They help place cells with a ‘broad perspective’,
an explanation where they are in environment, since the
metric ones focus only on details that determine the space.
Therefore, it is important that both inputs integrate for
place cells to have consistent place fields. Integration takes
place upstream of the place cells in entorhinal cortex (EC),
principal afferent area of hippocampal formation. Slight
changes in contextual cues lead to remapping, while even
greater changes in metric cues lead to only discrete alterations in firing pattern. Based on these findings, a model was
proposed. It states that non-metric inputs filter metric ones
(Figure 5). Using latter, one can precisely determine place
field location, but non-metrics decide which will be taken
into consideration. This explains previously mentioned
rate and global remapping. Having in mind that contextual
cues utilize a specific set of metric cues, considerable shifts
in context activate a different group of metric inputs. This
would lead to global remapping. Rate remapping, or slight
changes in firing pattern, will be noticed within the same
context and as a consequence of slight transformation of
spatial (e.g. box’s boundaries) dimension.
Certain neocortical lesions lead to loss and disruption of place
fields. This implies an inevitable role of different neocortical
areas in spatial processing: perirhinal cortex is important
for spatial reference and working memory; retrosplenial
Figure 4.
Multiple single-cell recordings. Rotation of firing fields (session 1 cortex for geometric properties and allocentric perception;
preceding session 2) follows rotation of arc-shaped cue card.
parietal for egocentric spatial processing; prefrontal for
Source: Place Cells in the Hippocampus. http://hargreaves.swong. egocentric short-term spatial performance associated with
webfactional.com/place.htm#O'Keefe%20and%20Dostrovsky,%20 motivation.6 Allocentric is object-to-object coding, while
1971. Updated July 2007. Accessed March 11, 2016.
egocentric is object-to-self coding. In other words, first
determines distance between objects and second between
field size and firing rate increase with removal of proximal, ourselves and objects.
and decrease with distal cue removal. Another change in size
can be shown in a chamber with sliding walls. Rescaling the Most prominent changes in firing field patterns are caused
compartment is followed by a proportional stretch in field by EC damage since input integration occurs in this region.
size. This leads to each place cell being tuned by a landmark EC receives information of each sensory modality and active
of a specific environment. Interestingly, only 15-50% of all cognitive processes. Most significant spatially modulated cells
place cells situated in dorsal hippocampus show activity. in medial EC are grid cells which perform path integration.
This is related to the fact that only a small number of cells This means that if all inputs, except speed and direction of
is adequate to represent the whole surrounding space with their movement, were removed, their firing fields would still
great accuracy (380 cells/1cm of space per 0.1s).4
be conserved. Other cells that have spatial inputs are head
direction cells in subiculum that follow head direction in
These are only some of the conclusions about hippocampal horizontal plane; boundary cells in subiculum, parasubiculum
spatial mapping and its field properties. This was to illustrate and medial EC that encode for environmental boundaries;
place fields as highly dynamic structures. It is clear that dif- and cells that encode object locations.7 They are highly
ferent inputs determine their characteristics.
multimodal and mutually connected.
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Fundamental Neuroscience
Jakobović AT. Place cells. pp. 73 – 78
Figure 5. Contextual inputs activate different sets of metric inputs.
Source: Jeffery KJ. Integration of the sensory inputs to place cells: What, where, why, and how? Hippocampus. 2007;17(9):775-785. doi:10.1002/
hipo.20322.
Copyright © 2007 Wiley-Liss, Inc.
To conclude, place cells receive different sets of highly heterogeneous inputs. Spatially modulated cells contribute in
forming a positioning system in the brain. It provides guidance to exploring new surrounding locations. It happens
moments after animal starts roaming in a test box. This map
can be used for working memory or stored for future use.
MEMORY
Certain place cells coactivate in different locations in specific order in time. This activation frame is a spatial context
for various memories. This means that during information retrieval, these cells would start emitting signals in
the same order during receiving and storage. Indexing
model explains memory formation and retrieval. For example, if Information_A (Place_Cell_1+Place_Cell_2 followed
by Place_Cell_3+Place_Cell_4) is stored at Location_1 and
Information_B (Place_Cell_1+Place_Cell_3 followed by Place_
Cell_2+Place_Cell_4) at Location_2, then invoking what is
stored at Location_1 would result in retrieving Information_A.
But what is it that determines Information_A retrieval and not
Information_B? One approach suggests it is a spatial context
in which the event had occurred. This context is provided
by place cells. Spatial memory retrieval is highly hierarchical. Overall layout recall is followed by an association of
details. After some time, details are forgot. A reader can do
an experiment for himself: think of a particular place; this
spatial context (layout) will soon provide you with different
associated information. It is impossible to remember all the
details as most memories fade away. This is persistent with
Ebbinghaus’s curve of memory.
Gyrus | Vol. 4 | No. 1 | January 2017
Nevertheless, it is still unclear how maps contribute to declarative, especially episodic, memory.8 Memory is a mental
act of information encoding, storing and retrieving. It can
be divided into explicit and implicit. Explicit or declarative,
which can be explicitly pronounced with words (e.g. facts),
consists of episodic and semantic. Episodic memory stores
personal experience — episodes.9 Hippocampus is essential
for memory formation as well as for creating spatial cognitive maps. It receives information via direct pathway (EC to
CA1) and indirect pathway (Figure 6).
Brief overview of memory formation is as follows. For a
sensory input of external events, sensory memory is formed.
Selective attention to this input determines long term stability
of place fields. Therefore, encoding is the first step in forming memories. It is a process by which our neural circuits
convert external stimuli to engrams. Engram is an internal
representation of environmental cue. For example, during
exploration of space, there is a weak synaptic potentiation
in CA3 from EC inputs (follow Figure 6). This memory trace
(engram) should now be stabilized. This process is known
as consolidation. Hence, encoding precedes consolidation.
Weakly potentiated synapses in CA3 afterwards evoke ripple
waves in CA1 neurons. These are of a specific frequency that
can induce long-term potentiation (LTP) in their efferent
synapses, presumably in cortex. This is how certain inputs
affect hippocampal place cells and their synaptic transmission.
LTP is a type of synaptic plasticity where synapse between
two neurons gets ‘stronger’. It is a molecular basis of learning.
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Fundamental Neuroscience
Jakobović AT. Place cells. pp. 73 – 78
ABNORMAL CONDITIONS
Function of place cells can be disrupted in certain cases.
Aging is a normal physiological process during which place
field’s plasticity decreases. Multiple factors have impact on
navigation and memory formation attenuation. Chronic
ethanol exposure, for example, impacts spatial cognitive
processing. Firing rate decreases and affects working and
long-lasting memory. Patients with Alzheimer disease (AD)
often exhibit spatial exploration and learning deficit. Cacucci
et al. (2008) recorded place cell activity in mouse model
of AD (Tg2576).10 Selected neurons were unable to code for
environmental locations, had disrupted LTP and increased
firing fields. Firstly, larger fields lead to nonspecific correlation with environment. Moreover, it results with failure in
cognitive map storage.
Figure 6. Trisynaptic circuit in hippocampus.
Source: Neves G, Cooke SF, Bliss TVP. Synaptic plasticity, memory and the hippocampus: a neural network approach
to causality. Nat Rev Neurosci. 2008;9(1):65-75. doi:10.1038/nrn2303.
Copyright © 2008 Nature Publishing Group
CONCLUSION
Place cells are neurons in hippocampus. They start
firing in a specific location which is called a place
field. Place fields are dynamic structures. Multimodal place cells respond to different metric and
non-metric stimuli. Experimental changes of those
cues lead to remapping, a slight or complete change
in firing pattern. In cooperation with other spatially
modulated cells, they provide context for memory
formation. Place cells form a cognitive map of space.
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It can be used for navigation and/or stored for
future use. This process can be interfered during
alcohol abuse, Alzheimer disease or aging. Further
research of place cell pathology could provide us
with better understanding of spatial processing
while translation of these findings to clinical practice
could improve life quality of AD patients. restoration,
ovulation induction and pregnancy.
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Fundamental Neuroscience
References:
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3. Muller RU, Kubie JL. The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells.
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Philos Trans R Soc B Biol Sci. 1998;353(1373):1333–40.
5. Jeffery KJ. Integration of the sensory inputs to place cells: What, where, why, and how? Hippocampus. 2007. p. 775–85.
6. Poucet B, Lenck-Santini PP, Paz-Villagrán V, Save E. Place cells, neocortex and spatial navigation: A short review. In: Journal
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7. Bush D, Barry C, Burgess N. What do grid cells contribute to place cell firing? Trends Neurosci. 2014;37(3):136–45.
8. Cells P, Cells G, Moser M, Rowland DC, Moser EI. Place Cells, Grid Cells, and Memory. 2015;1–16.
9. Smith DM, Mizumori SJY. Hippocampal place cells, context, and episodic memory. Hippocampus. 2006;16(9):716–29.
10. Cacucci F, Yi M, Wills TJ, Chapman P, O’Keefe J. Place cell firing correlates with memory deficits and amyloid plaque burden
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PLACE CELLS (POZICIJSKE STANICE)
Sažetak
Place cells su piramidni neuroni u CA1 i CA3 poljima hipokampusa. Odašilju niz signala na točno određenoj lokaciji u
prostoru koju zovemo place field. Neke stanice imaju više polja kada se nađu u većem okolišu. Svaka stanica pokriva
jedan dio prostora. To im omogućava formiranje mentalne karte nekog okruženja. Ovaj pristup naziva se teorijom
kognitivne mape. U različitim situacijama, obrazac odašiljanja signala se mijenja. Ove promjene se mogu opaziti u
različitim pokusima. Postoje dvije vrste aferentnih signala koji određuju emitirajuće signale. Metrički ulaz oslanja se
na vid i pokrete, dok nemetrički (kontekstualni) ulaz uključuje boju, miris, nagrade itd. Kontekstualni ulaz određuje
koje će se metričke odrednice upotrijebiti. Oni interagiraju u entorinalnom korteksu (EC). Glavne prostorom modulirane stanice u EC su grid cells. Druge obuhvaćaju head direction cells i border cells lokalizirane u drugim kortikalnim
područjima. Sve pridonose formiranju mentalne karte. Ona se može koristiti u radnom pamćenju ili biti pohranjena
za buduću uporabu. U nekim slučajevima, navedene funkcije mogu biti poremećene. Akutna i kronična konzumacija
alkohola reducira staničnu električnu aktivnost. U Alzheimerovoj bolesti, stabilnost polja i prostorno pamćenje su
poremećeni. Izuzev patoloških slučajeva, starenje, normalan fiziološki proces, dijeli slične značajke.
ključne riječi: hipokampus, place cell, place field, prostorno pamćenje, remapping
Received March 15, 2016.
Accepted November 28, 2016.
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