The Navigation System of the Brain - Indian Academy of ...

401RESONANCE May 2015

GENERAL ARTICLE

The Navigation System of the Brain

2014 Nobel Prize in Physiology or Medicine

Prasanna Venkhatesh V

Keywords

Hippocampus, cognitive map,

place cells, grid cells.

“It is fair to say that, in general, no problems have been

exhausted; instead, men have been exhausted by the prob-

lems. Soil that appears impoverished to one researcher re-

veals its fertility to another. Fresh talent approaching the

analysis of a problem without prejudice will always see new

possibilities – some aspect not considered by those who believe

that a subject is fully understood. Our knowledge is so frag-

mentary that unexpected findings appear in even the most

fully explored topics. We must bear in mind that because

science relentlessly differentiates, the minutiae of today often

become important principles tomorrow.”

– Santiago Ramon y Cajal

The ability to navigate in space is one of the fundamental func-

tions of the brain. It depends on the ability to have a sense of

position which in turn is interlinked with the sense of direction,

distance and the knowledge of the earlier positions through which

one has travelled. You depend on it for your everyday activities

ranging from finding your car in a parking lot to commuting to

your workplace. The 2014 Nobel Prize in Physiology or Medicine

was awarded to John O’Keefe, May-Britt Moser and Edvard

Moser for their discoveries of nerve cells in the brain that consti-

tute a positioning system that enables one to have a sense of

position and navigation (Figure 1).

Edward Tolman’s Idea of Cognitive Maps

Some of the early experiments on spatial learning of animals were

performed by psychologist Edward C Tolman during the late

1940’s. Skinner’s behaviourist paradigm dominated psychology

during that period and most psychologists focussed on functional

relations between stimulus and response, without considering the

Prasanna Venkhatesh V is

currently a graduate

student at the Center for

Neuroscience working with

Aditya Murthy. He is

working on voluntary

control of reaching and

pointing movements. His

research interests include

movement control, neural

basis of animal behaviour,

optogenetics and social

neuroscience.

402 RESONANCE May 2015

GENERAL ARTICLE

role of internal representations. Although Tolman was firmly

behaviourist in his methodology, he wanted to use behavioural

methods to understand the mental processes of humans and other

animals.

His experiment which was conducted over several days involved

three groups of rats running through a maze. For Group 1, food

was kept at the end of the maze. For Group 2, no food was kept,

and for Group 3, food was kept only on day 11. The Group 1 rats

quickly learned to rush to the end of the maze without making

many errors, while Group 2 rats wandered in the maze but did not

preferentially go to the end. Rats in Group 3 essentially showed

the same behaviour as Group 2 rats until food was introduced on

day 11; they quickly learned to run to the end of the maze and

made fewer errors like the Group 1 rats by the next day. This

showed that the Group 3 rats had learned about the organisation

of the maze even without the reward.

Tolman reasoned that animals did not passively react to the

external stimuli. Rather, they learnt facts about the world and

used it as and when required. This suggested that there was some

kind of ‘latent learning’, i.e., they were using the knowledge in

the preceding trials to build a map and utilize it when they were

motivated to do so. He concluded that spatial learning consists of

building cognitive maps in the nervous system and are not mere

stimulus response connections and that these maps can range

Figure 1. Winners of 2014

Nobel Prize in Physiology or

Medicine: John O’Keefe (left),

May-Britt Moser (middle),

Edvard Moser (right).

Photocredits: O’Keefe: David

Bishop/UCL; M.-B. and E.

Moser: Geir Mogen/Kavli Insti-

tute for Systems Neuroscience.


GENERAL ARTICLE

from a simple narrow strip to a broader comprehensive map. This,

however, did not address where in the brain these functions may

be localizedand howthebraincomputes suchcomplex behaviours.

Tolman’s cognitive map theory faced fierce criticism from the

behaviourists who believed that complex behaviours in animals

are achieved by chains of sensory-motor response relationships.

The following is an excerpt from Tolman’s paper in 1948 p.192

on cognitive maps in rats and men.

“We believe that in the course of learning, something like a field

map of the environment gets established in the rat’s brain… The

stimuli … are usually worked over ... into a tentative, cognitive-

like map of the environment. And it is this tentative map, indicat-

ing routes and paths and environmental relationships, which

finally determines what responses, if any, the animal will finally

release.”

The Hippocampus and its Function

During the late 1950s, the majority of the clinical studies sug-

gested that the hippocampus (an area in the brain deep inside the

temporal lobe) by and large plays a fundamental role in long-term

associative memory. This idea was derived from the famous

report in 1957 by William B Scoville and Brenda Milner describ-

ing the results of surgical removal of the hippocampi in patient ‘H

M’ in an attempt to alleviate his epileptic seizures. After the

surgery, H M suffered from a severe anterograde amnesia (inabil-

ity to form new episodic memories) and partial retrograde amne-

sia (inability to recall memories that occurred before the surgery).

This report played an important role in creating the link between

the hippocampus and memory.

For a long time investigations were directed towards understand-

ing the underlying mechanisms and the role of the hippocampus

in the formation of memory. Several patterns of electrical activity

have been recorded from the hippocampus, and they have been

correlated with behavioural or psychological states. During the

mid-1960s, C H Vanderwolf placed a large electrode into the

For a long time,

investigationswere

directed towards

understanding the

underlying

mechanisms and the

role of hippocampus

in the formation of

memory.


GENERAL ARTICLE

hippocampus of a freely moving rat and recorded the EEG

activity during a wide range of behaviours shown by the animal.

He found that the theta rhythm in the EEGmostly correlated with

certain behaviours of the animal like orienting, sniffing and

walking or not at all, during eating, drinking, grooming, quiet

sitting, and slow wave sleep. It was also known by then that rats

with lesions in the hippocampus had ‘spatial problem solving’

deficits. These results indicated that there was some sort of

spatial processing happening in the hippocampus. Refer to Box 1

for more on the history of hippocampal anatomy and function.

Discovery of Place Cells in the Hippocampus

In the late 1960’s, single-cell neuronal recordings in awake,

unrestrained rats was a cutting-edge technology. With the help of

the brain atlas, tiny wire electrodes were guided to specific areas

of interest in the brain. When the electrode tip is close to a neuron,

the electrode can record the action potentials from that neuron.

During the experiment the action potentials were recorded along

with x, y coordinates of the rat’s location as viewed from above

with the help of a small light fixed to the rat’s head. John

O’Keefe, who was by then expert at recording neurons using this

technique in awake-behaving rats, recorded the hippocampus

neuronal activity when the animal was doing a variety of

behaviours. Anyconservativeneurophysiologist at that timewould

have considered this experiment radical because sensory and

motor areas were easy and reliable targets and decoding the

Figure 2. a) Place cell in the

hippocampus. b) Grid cell in

the medial entorhinal cortex.

Spike locations are repre-

sented as red dots and su-

perimposed on the animal’s

trajectory in the recording

enclosure as black. Whereas

most place cells have a single

firing location, the firing fields

of a grid cell form a periodic

triangular matrix tiling the

entire environment available

to the animal.

Reprinted from Trends Cogn

Sci., 14 (12), Derdikman D and

Moser EI, A manifold of spatial

maps in the brain, 562, 2010,

with permission from Elsevier.


GENERAL ARTICLE

Box 1. History of Hippocampal Anatomy and Function

The hippocampus lies deep within the medial temporal lobes of the human brain with a group of neuronal

networks quite distinctly organised compared to the other areas of the brain.The Bolognese anatomist Giulio

Cesare Aranzi (circa 1564) was credited for coining the name ‘hippocampus’ to this area of brain because

of its remarkable appearance similar to that of a small marine fish that belongs to the genus Hippocampus.

Hippocampus is the greek name for a mythical sea monster, hippos meaning ‘horse’ and kampos meaning

‘sea monster’ in ancient greek. When the hippocampus is cut in cross section, it resembles a ram’s horn.

So ancient anatomists named it cornu ammonis (abbreviated as CA in modern nomenclature) which in latin

literally means horn of the ram. CA (subdivided as CA1, CA2,CA3 and CA4) is one of the two interlocking

gyri composing the hippocampus, the other being the dentate gyrus (DG). The unique arrangement of all

the cell population into single layers had attracted the attention of many investigators of the central nervous

system of the late nineteenth century. One of the pioneers to illustrate the unique organization of the

hippocampus is the Italian anatomist Camilio Golgi in 1886 (Figure A, left). Santiago Ramon y Cajal in

1911 clearly illustrated the hippocampus of rodents (Figure A, right) with arrows showing his interpre-

tation of the likely direction of the information flow using the staining method developed by Golgi. The

early anatomical studies of the hippocampus were important during the nineteenth century controversy

between the neuron doctrine (by Ramon y Cajal) and the reticular theory (by Golgi). Golgi used his

observations of the hippocampal formation to support his arguments for the reticular theory. During the

ninteenth century and the early twentieth century, the hippocampus was believed to have several functions

like olfactory, emotion and attentional control. The idea that the hippocampal formation is intimately

associated with memory came into existence mainly due to the observations made on the patient ‘H M’ by

William Scoville and Brenda Milner in 1957.

Figure A. (Left) Golgi's schematic drawing summarizing

the structure of the hippocampus which was published in

the book, Golgi, C. Sulla fina anatomia degli organi centrali

del sistema nervoso (On the Fine Structure of the Central

Organs of the Nervous System). Milan,Ulrico Hoepli, 1886.

Courtesy: Wikipedia.

(Right) The famous drawing of the hippocampus by

Santiago Ramon y Cajal was published in his book, Cajal

SR. Histologie du système nerveux de l’homme & des

vertébré (Histology of the nervous system of humans and

vertebrates), Paris, Maloine, 1909–1911.

Courtesy: https://archive.org (Identifier: histologiedusyst01ram),

Wikipedia.

1. Chapter 2, P Andersen, R Morris, D Amaral, T Bliss, J O’Keefe, The hippocampus book, Oxford University

Press, Oxford, 2006.

2. C Golgi, M Bentivogli, L Swanson, On the fine structure of the pes hippocampi major, Brain Res. Bull., Vol.54,

pp.461–483, Translated from Golgi C, 1886.

3. Prasanna Venkhatesh V, Santiago Ramon y Cajal: The Father of Neuroscience, Resonance, Vol.15, pp.968–

976, 2010.


GENERAL ARTICLE

neuronal data and correlating it with the behaviour from areas

deep inside the brain was like finding a needle in a hay stack.

However, this approach proved quite fruitful for John O’Keefe

and his student Dostrovsky in 1971, because they discovered

neurons in the rat hippocampus that showed activity correlated to

the rat’s location within its environment. They called these neu-

rons ‘place cells’ (Figure 2a).

Place cells fire when the animal is moving in a specific location in

the environment, which corresponds to the place field of that

particular neuron. These place cells were first found in the

pyramidal cell layer of area CA1 of the hippocampus. Later, other

groups showed that area CA3 of the hippocampus also has place

cells. With extensive research, he concluded the following in his

1976 paper. Place cells firing in a part of the animal’s environ-

ment is not because of something the animal does there or because

of its motivation for going to that place. Rather, they appear to be

a cognitive process, signalling the animal’s position within an

environment irrespective of its behaviour and motivational state

or the reward properties of that place. The discovery of place cells

by John O’Keefe in the hippocampus created a new surge of

interest in the field in spite of the skepticism from a few investi-

gators [18].

The Influential Book by O’Keefe and Nadel

O’Keefe and Lynn Nadel authored an influential book called the

The Hippocampus as a Cognitive Map in 1978, delineating the

theoretical foundation for the hippocampal function and the

importance of the relationship between place cells and cognitive

map theory. According to the cognitive map theory, there must be

an abstract representation of the environment in the brain and the

map may be used by the animal to calculate efficient paths. The

theory put forth by O’Keefe and Nadel was influenced by Edward

Tolman’s theory about ‘cognitive maps’ in rats.

There was, however, a fundamental conceptual difference be-

tween Tolman’s original formulation of cognitive maps and the

cognitive map theory formulated in the book. In rodents, Tolman

Place cells fire

when the animal is

moving in a

specific location in

theenvironment,

which corresponds

to the place field of

that particular

neuron.


GENERAL ARTICLE

linked the cognitive maps to spatial information; in humans, he

associated cognitive maps more to events and emotions without

referring to a spatial framework. On the other hand, O’Keefe and

Nadel’s cognitive maps ascribed increased importance to spatial

framework in all animals and also asserted that the hippocampus

is the core of a neural memory system providing an objective

spatial framework within which the items and events of an

organism’s experience are located and interrelated. That is to say,

the hippocampus not only provides a spatial map but also pro-

vides a platform for embedding context-dependent memory.

The figures in the book and in the early papers were marginally

convincing, and there was no quantitative analysis. Only in the

mid 1980’s, computer-based data acquisition produced a con-

vincing presentation of the robust phenomenon of place cells.

Several studies have tried to identify the cues which are respon-

sible for the selective firing of neurons in the place field. It was

clear that the notion of place constructed by the place cells was at

least in part due to the cues available to the animal at that location.

Experimental results showed that place cells do not respond to

particular stimuli but will continue to indicate the animal’s posi-

tion as long as subsets of spatial cues are available. Also, loca-

tions in the environment were not mapped onto the hippocampus

in any orderly topographic manner. O’Keefe and Nadel envi-

sioned that if all the place cells are connected appropriately, it

would form a spatial map of the environment.

Place-Cell Remapping

A couple of papers by Bob Muller and colleagues in 1987 left

little room for the place-cell skeptics who criticised the spatially

correlated activity of these cells as being confounded by spatially

correlated cues. The main evidence they showed in their articles

was that, minimization of local sensory cues did not diminish

spatial specificity of neurons. In fact, this drove the field to such

an extreme, that most of the experiments were conducted in cue-

poor environments long after the convincing demonstration of re-

presentation of ‘space’ by ‘place cells’ and not anything sensory.

Experimental results

showed that place

cells do not respond

to particular stimuli

but will continue to

indicate the animal’s

position as long as

subsets of spatial

cues are available.


GENERAL ARTICLE

These two papers also answered the following questions: How

are different environments represented in the hippocampus?When

an animal goes from one environment to a second environment,

how will the spatial maps respond? Are there rules and regulari-

ties? These papers also contained the discovery that place-cell

maps are completely different in two environments: a phenom-

enon later called ‘remapping’. They found that, if a place cell has

firing fields in two environments, knowing the location of the

firing field in the first environment will not predict the location of

the firing field in the second environment. Changing the shape of

an enclosure invariably induces full remapping. To be brief, the

hippocampal map of space is sensitive to non-spatial factors and

understanding these factors will be essential in decoding the

relationship between hippocampal maps and memory.

Head Direction Cells and Boundary Cells

In order to maintain the spatial orientation and to guide naviga-

tion, an animal must have knowledge of its location, displacement

or distance and direction from that location. By now, we know

that place cells could be used to identify familiar environmental

locations. Also, therewas a speculation that the oscillations of the

theta rhythm1 of the LFP2 (local field potentials) that occurred

during running could measure the distance. The missing piece in

the puzzle is that if the hippocampal system were to guide

navigation, it needed a sense of direction, which was predicted by

O’Keefe and Nadel in their 1978 book. In 1984, Jim Ranck

reported that cells in the post-subiculum of the rat brain dis-

charges whenever the animal’s head points to a specific direction,

independent of their location or behaviour, thus providing a

compass signal. Head direction cells are found in many brain

regions like the anterior thalamic nuclei, post and parasubiculum

and also in the entorhinal cortex. Two papers in 1990 from Jim

Ranck’s group studied in detail the properties of the head direc-

tion (HD) cells. They found that HD cells are strongly modulated

by environmental cues such as visual landmarks.

The vestibular system and the self movement cues play a critical

2 The local field potential (LFP)

refers to the electric potential in

the extracellular space around

neurons. The LFP is a widely

available signal in many record-

ing configurations, ranging from

single-electrode recordings to

multi-electrode arrays.

1 Theta rhythm is an oscillatory

pattern in electroencephalo-

graphy (EEG) signals recorded

either from inside the brain or

from electrodes glued to the

scalp. Two types of theta rhythm

have been described. The ‘hip-

pocampal theta rhythm’ is a

strong oscillation that can be

observed in the hippocampus

and other brain structures. ‘Cor-

tical theta rhythms’ are low-fre-

quency components of scalp

EEG, usually recorded from hu-

mans. Cortical theta rhythms

observed in human scalp EEG

are a different phenomenon, with

no clear relationship to the hip-

pocampus. In human EEG stud-

ies, the term theta refers to fre-

quency components in the 4–7

Hz range, and the hippocampal

theta refers to a cycle of 6–8 Hz

range.


GENERAL ARTICLE

role in the generation of head direction signals. HD cells provide

a continuous signal that an animal will use to guide its navigation

and maintain orientation. Neil Burgess and O’Keefe in 1996

demonstrated that the boundaries of an environment can elicit

modulation in the location-specific firing of place cells. They

stretched/compressed the walls of the chamber and correspond-

ingly the place fields remapped. Burgess and colleagues formu-

lated a ‘boundary vector cell’ model that not only explained the

existing data but successfully predicted how cells would respond

to new manipulations. It is remarkable that the model predicted

the existence of boundary related cells and almost 10 years after

the prediction, boundary cells were discovered in a number of

brain regions.

Hippocampal Circuitry and the Entorhinal Cortex

The neuronal antecedents to the place cells were not understood

clearly. The obvious line of investigation was whether the map is

located within the hippocampus or it is constructed elsewhere and

merely transferred to the hippocampus. Anatomically entorhinal

cortex is the major source of cortical input to the hippocampal

place cells. This is substantiated by the findings that entorhinal

damage causes serious deficits in spatial problem-solving tasks as

hippocampal lesions do.

Important insights about the role of the entorhinal cortex as a

major input to the place cells came from lesion studies on the

dentate gyrus (DG) as reported in McNaughton et al, 1989. They

found that the place cells fired sharply even after a major lesion in

dentate gyrus, while the connections of the CA3 and the entorhinal

cortex were still intact. Clear evidence came from the Moser

group (led by EdwardMoser and May-Britt Moser) in 2002; they

showed that even when the connections of the CA3 and the CA1

were disrupted, CA1 still exhibited spatial firing. This negated

the possibility that the internal hippocampal circuitry was in-

volved in the computation of the spatial signals. This study

suggested that, the likely input to the CA1 place cells in the dorsal

hippocampus is from the entorhinal cortex. The connectivity of


GENERAL ARTICLE

the hippocampal formation (DG, CA1, CA3 and subiculum) and

the parahippocampal areas (PrS, PaS, LEC and MEC) can be

found in Figure 3.

The first study about the spatial activity in the entorhinal cortex

was reported by Quirk et al, in 1992. They found that neurons in

Figure 3. Anatomy of hippocampal formation and parahippocampal region. a) Shows the right hemisphere

of a rat brain, with a focus on the hippocampal formation and the parahippocampal region. The borders and

the extent of individual subregions are colour-coded. b) The current standard connectivity model of the

hippocampal formation and parahippocampal region. presubiculum (PrS), parasubiculum (PaS), dentate

gyrus (DG), lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC).

Reprinted by permission from Macmillan Publishers Ltd: Nature Review Neuroscience, doi:10.1038/nrn3766,

2014. [22]


GENERAL ARTICLE

the medial entorhinal cortex that project to intermediate hippoc-

ampus displayed weak spatial modulation compared to that of the

hippocampal cells. Anatomically, the entorhinal cortex contains

two major subdivisions – the medial and the lateral. By the late

90’s it became clear that the medial entorhinal cortex (MEC)

shows a dorsal-to-ventral organization in which the most dorsal

parts project exclusively to the dorsal hippocampus and the most

ventral parts only to theventral hippocampus. Thelateralentorhinal

cortex (LEC) shows a medial-to-lateral organization of projec-

tions to the hippocampus. Until 2004, most of the recordings of

spatial cells in the entorhinal cortex were from intermediate or

ventral parts of either LEC or MEC. These studies were not ideal

because, the ventral region projects primarily to the ventral

hippocampus, where place fields are large, and exhibit minimal

spatial variation in small environments. The cells from the most

dorsal parts of the entorhinal cortex, which provide the connec-

tions to the dorsal hippocampus where place cells were discov-

ered, were not investigated. With the help of the neuroanatomist,

Menno Witter, the Mosers in 2004 recorded from the dorso-caudal

region of the medial entorhinal cortex. They found that superficial

layers showed discrete firing fields (only the cell layers II and III of

the dorso-caudal medial entorhinal cortex (dMEC)) of the animal’s

current location as that of the place cells with each cell having

multiple firing fields. This study confirmed the hypothesis that the

spatial information is processed upstream of the hippocampus.

Discovery of Grid Cells in the Entorhinal Cortex

The Moser group noticed that the fields in the 2004 recordings

from the dMEC followed a regular organization with optimal

distance between them. In order to have a better understanding of

the spatial organization of the firing fields, the same cells were

subsequently recorded in larger environments, including boxes

with surface areas that were more than three times larger than

those of previous studies.

In 2005, the Mosers published a paper that provided a detailed

description of the spatial properties of the dMEC. The most

The most striking

and remarkable

observation in that

study was the

spatial regularity (a

tessellated

pattern) of the

neuronal firing


GENERAL ARTICLE

striking and remarkable observation in that study was the spatial

regularity (a tessellated pattern) of the neuronal firing in the layer

II of the dMEC while the rat was walking in the enclosure (Figure

2b). The firing fields of the neurons in the layer II of dMEC

formed a beautiful grid like structure of tessellating equilateral

triangles; in other words the firing locations form the vertices of a

hexagonal grid, representing the entire space traversed by the animal.

The basic unit of the tessellated spatial firing pattern is called a grid

and the cells that elicit such a firing pattern are called ‘grid cells’. The

characteristic features of the grids are thespatial phase, spacingof the

grid and their orientation (Figure 4). The temporal and spatial auto

correlation analysis suggested that the recurring peaks in the

auto-correlograms did not reflect artefacts in the analytical proce-

dures.

Properties of Grid Cells

The questions that immediately arose are the following: how is

the grid cell population organized anatomically? Is the same

pattern of spatial firing seen in all layers? What are the factors

that determine the spacing, orientation and the size of the field?

The Moser group found that the spacing and the field size

increased from the dorsal to the ventral part of the dMEC. A key

question that pops up is, how much of external cues contribute to

the locations of the discharge by grid cells, and also whether the

cues are necessary to maintain the grid structure. Repeated tests

in the same environment showed that the vertices of the grids are

located at identical positions.

Figure 4. Parameters that

define grid cells. Cartoons of

firing patterns of pair grid cells

shown in green and blue.

Spatial phase is the position

of the gird vertices in the x–y

plane. (Left panel) Black and

red crosses represent the

phases of two different grid

cells. (Middle panel) Spacing

in the grids is the distance

between anyvertex of the grid

and the six adjacent vertices

in the rate map or in the

autocorrelogram. (Right

panel) Orientation of the grid

vertices is defined by the lines

that intersect the grid verti-

ces indicated in black and

red.

Reprinted by permission from

Macmillan Publishers Ltd: Na-

ture Review Neuroscience ,

doi:10.1038/nrn3766, 2014

[22].


GENERAL ARTICLE

However, when the landmarks are rotated, the grids rotate. Visual

cue deprivation studies showed that the grid was maintained even

in darkness and the grid space remains the same. Then the

question is – what determines the phase and orientation of the grid

cells? Although configuration of the environment may not be

essential for producing a grid pattern, what seem to be the

essential determinant of the phase and orientation are the land-

marks.

There are two conclusions which are derived from these results;

first, the external cues exert a significant influence over the phase

and orientation. Second, from the visual deprivation studies, the

authors concluded that self motion (vestibular-kinesthetic)3 is the

only likely source of maintained discharge in the grid cells in

moving animals. Also, the invariance of the firing pattern for

change in direction and velocity explains that the changes in

velocity and heading must be integrated over time to enable a

constant representation of spatial relationship between positions

which is called ‘path integration’4 [10,22].

Latest Findings

I am listing here some of the interesting recent findings in the grid

cell and place cell literature. The readers can look into the recent

reviews for more information. [19–23]

1. In 2011, Deshmukh and Knierim discovered that the Lateral

Entorhinal Cortex (LEC) represents both spatial and non-spatial

information. They found that some LEC neurons fire at the

location of the objects in the environment as well as showing that

LEC has ‘place cells’ in the presence of objects. This is an

important contribution because LEC and MEC may be providing

complementary spatial information to the hippocampus – MEC

provides path integration derived space while LEC provides

sensory derived space (as well as object related information).

2. Eichenbaum’s group, in 2011, reported that cells in the

hippocampal formation code for time and they called these ‘time

cells’.

4 Path integration is the process

of summing up information about

direction and distance travelled,

in order to keep track of one’s

relative position. Path integra-

tion is hypothesized to be the

basis for the formation of the

‘place code’ the hippocampus

uses to encode spatial memo-

ries. ‘Dead reckoning,’ tradition-

ally used by seafarers uses a

combination of path integration

(compass direction and speed

measured in ‘knots’) and taking

a fix on actual position when

‘landmarks’ are available. This

is akin to the emerging pattern

of MEC representing path inte-

gration derived space while LEC

representing landmark derived

space.

3 The vestibular senses (the sen-

sations of body rotation and of

gravitation and movement) arise

in the inner ear; the sense or-

gans are the hair cells that send

out signals over the auditory

nerve. Movement of the body’s

muscles, tendons, and joints is

also monitored by mechanore-

ceptors in these structures and

this process is called kinesthe-

sis.


GENERAL ARTICLE

3. Recent work has shown that within a single animal, grid cells

can be clustered into 4 or 5 modules, such that grid scale increases

in a discrete fashion between one module to the other. The other

interesting finding is the fact that, when the grid spacing in each

module is defined by the dimensions of a fitted ellipse, the ratio

grows in leaps of ~ 2. The geometric progression defined by this

constant scale factor has been suggested to be optimal for repre-

senting environments at high spatial resolution.

4. There are several computational models that try to understand

the relationship between the grid cells, head direction cells,

border cells and place cells.

5. The grid and place cell systems are found in many mammalian

species including humans. Recently researchers have found place-

like cells in hippocampus and grid cells in the entorhinal cortex of

other mammalian systems like non-human primates, bats and

humans by directly recording from these areas. The fact that there

exists a similarity inmostmammals, in thehippocampal-entorhinal

structure (with navigational capacity) suggests that the place cell-

grid cell system is robust, functional and conserved in vertebrate

evolution.

Concluding Remarks

The discovery of place cells and grid cells by John O’Keefe,

Edvard Moser and May-Britt Moser has clearly revolutionised

our understanding of the cognitive functions of the brain, espe-

cially the spatial navigation. These findings open a lot of avenues

for future research in both memory and spatial navigation, since

the link between the two are yet to be understood.

Acknowledgements

I would like to thank

Sachin Deshmukh and

Kousik Sarathy for the

critical comments and for

the discussions. I also ac-

knowledge Divija Rao,

Namrata Iyer and Ranjani

Seshadri for their helpful

inputs.

Suggested Reading

[1] E C Tolman, Cognitive maps in rats and men, Psychol Bull., Vol.55, pp.189–208, 1948.

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Address for Correspondence

Prasanna Venkhatesh V

Center for Neuroscience

Indian Institute of Science

Bengaluru 560 012, India

Email: [email protected]

[email protected]

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