The document summarizes the brain's internal navigation system. It describes the discovery of place cells in the hippocampus by John O'Keefe in 1971 which fire when a rat is in a particular location and help form a cognitive map. May-Britt Moser and Edvard Moser discovered grid cells in the entorhinal cortex in 2005 which form a hexagonal grid-like pattern and act as a coordinate system. Other key cells involved are head direction cells and boundary cells. Together these cells allow an animal to know its location, direction and distance traveled to navigate spaces. Damage to the hippocampus, as seen in patient H.M., impairs this ability to form new spatial memories.

1. The Brain’s Internal
GPS*
1*The review of paper “The Navigation System of the Brain” by Prasanna Venkhatesh V
Aafreen Ansari
14/BT/01
Department of
Biotechnology
(VI Sem)

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Winners of 2014 Nobel Prize in
Physiology or Medicine:
John O’Keefe (left) for his discovery
of Place cells,
May-Britt Moser* (middle),
Edvard Moser* (right).
*for their discovery of Grid cells.

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Edward Tolman ‘Latent Learning’
experiment with rats:
PROCEDURE:
• The experiment 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.
OBSERVATION:
• The Group 1 rats quickly learned to rush to the
end.
• Group 2 rats wandered in the maze but did not
go to the end.
• Group 3 showed the same behaviour as Group 2
rats until food the food was kept.
INFERENCE:
• The Rats learnt facts about the maze and used it when required.
• There was some kind of ‘latent learning’, i.e., hidden learning.

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Cognitive map
Cognitive map
• Idea was first developed by Edward C.
Tolman after his LATENT LEARNING
experiment.
• Is a mental picture or image of the layout
of one’s physical environment
• acquire, code, store, recall, and decode
information about different locations.

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PATIENT H.M.(HENERY MOLAISON )
• At the age of 7 HM had a bicycle
accident which left him with interactive
epilepsy
• In 1953 a surgery was performed
• His hippocampus, was removed in the
surgery.
1926-2008
Image Source: Wikimedia Commons

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The surgery came out to be
affective and gave him a
seizure free life
BUT! HM started suffering
• A severe anterograde amnesia
• Partial retrograde amnesia
• As he aged he could no longer
remember his own face
HIPPOCAMPUS ABSENT

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Where is it located?
• The hippocampus is
located in the MEDIAL
TEMPORAL LOBE of the
brain beneath the cortex..
Image Source: Wikimedia Commons
Hippocampus

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Hippocampus Anatomy
• The name “Hippocampus” comes from the Greek for
seahorse
• It is named so because of its resembles a seahorse
Image Source: Wikimedia Commons

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• Hippocampus is a part of a large section
of temporal lobe called Hippocampal
Formation.
• The Hippocampal Formation consists of
following sections
 Hippocampus
 Hippocampal or Parahippocampal
gyrus
 Entorhinal Cortex
 Subiculum
 Dentate Gyrus

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Along with being compared to seahorse it is also
compared to the horn of Egyptian God Zeus
Ammon hence its former name was cornu
ammonis(CA)
Hippocampus is anatomically sub divided into
FOUR Regions:
1) CA1
2) CA2
3) CA3
4) CA4

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What does it do?
Hippocampus
• Closely aligned to memory formation.
• Involved in transition of short term memory to long
term memory.
• Helps in Spatial navigation.
• Is a part of limbic system –emotion control system.

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TRANSFER OF SENSORY CUE IN AND OUT OF
HIPPOCAMPAL FORMATION
FORNIXTHALAMUS &
HYPOTHALAMUS
CEREBRUM

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IMPORTANT NERVE CELLS OF OUR
BRAIN’S GPS SYSTEM
Four Important cells involved in the GPS system:
1) Place cells (position
specific)
2) Grid cells (coordinate
specific)
3) Head direction cells
4) Border cells or Boundary
cells

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PLACE CELLS
 In 1971 John O’Keefe discovered the first
component of our positioning system
 Certain nerve cells were activated every time a
rat changed its position .
 He named those nerve cells “PLACE CELLS”.
 These cells are present in the area of the brain
called hippocampus (CA1&CA3).
 The position of activation of these cell in
environment is called PLACE FIELD.
 Place cells together forms a cognitive map.
Firing patterns of 8 place
cells recorded from
the CA1 layer of a rat.
Image Source: Wikimedia Commons

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• Single-cell neuronal recordings in awake,
unrestrained rats ware performed
 With 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.
• the hippocampus neuronal activity was
recorded when the animal was doing a
variety of behaviours.
Discovery of place cells(1960)
SINGLE-CELL NEURONAL
RECORDING
Image Source: Wikimedia Commons

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• He found that certain nerve cells were activated every
time the rat changed its position in the room
• These neurons where named Place cells.
• The environmental area in which they showed activity is
called place field.
Image Source: Wikimedia Commons

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DISCOVERY OF GRID CELL
• Single-cell neuronal recording done for Medial
Entorhinal Cortex(MEC)
• Recordings are made as the rat moves around freely.
• Each Cell had firing field with multiple peaks.
• The peak formed a grid like structure of repeating
equilateral triangles with optimal distance between
them.
• Formed the vertices of a hexagonal grid
• It represents the entire space travelled by the animal.
• The basic unit of this pattern is called a grid.
• The cells that draw such a firing pattern are called ‘grid
cells’.
FIELD FIERING OF A
NERVE CELL IN
ENTORHINAL CORTEX

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PROPERTIES OF GRID CELL
• That grid cells form a coordinate system that helps our brain read out the
cognitive map in the hippocampus.
• Involved in measuring movement distance.
• Similar to the grids found on a map.
COMPARISION
BETWEEN
GRID CELL
AND MAP
GRID

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HEAD DIRECTION CELLS
• Neurons that function as a compass
• Activates when the animal's head
points in a specific direction
• Different head direction cells fire in
different direction
• Present in no. of interconnected
brain region including entorhinal
cortex & subiculum.
James Ranck Jr.

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ACTIVITY LEVEL OF INDIVIDUAL HEAD DIRECTIONAL CELL WRT
HEAD DIRECTION

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BOUNDARY CELL
• Boundary cells are neurons that respond to
the presence of an environmental boundary
at a particular distance and direction.
• Present in subiculum and entorhinal cortex.
• Boundary can be a wall or a drop or any
obstacle.
• When ever a boundary appears the firing of
these cells highly rises.

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PLACE CELLS,GRID CELLS,HEAD
DIRECTION CELLS,BORDER
CELLS together form a complex
navigation network within the
brain. Hence acts as our
BRAIN’S INTERNAL GPS
CONCLUSION

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FUTURE ISSUES
• How is the grid pattern generated during
nervous system development?
• What is the function of lateral entorhinal
cortex?
• How is the memory encoded?
• Function of many areas are unknown.

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REFERENCE
• Prasanna Venkhatesh V, The Navigation Sysem of the Brain: 2014 Nobel Prize in
Physiology or Medicine, Volume 20, Issue 5 May, 2015, pp 401-415
• J O’Keefe, L Nadel, The hippocampus as a cognitive map.Clarendon, OxfordUniversity
Press, 1978. (Free online Version: http://www.cognitivemap.net/)
• T Hafting, M Fyhn, S Molden, MB Moser, EI Moser, Microstructure of a spatial map in
the entorhinal cortex, Nature, Vol.436, pp.801–806, 2005.
• Spatial Perception and Memory lab: http://derdiklab.technion.ac.il/scientific-
background/
• Gary Stix , Scientific American, October 6, 2014:
https://blogs.scientificamerican.com/talking-back/discovery-of-brain-s-navigation-
system-wins-2014-nobel-prize-in-medicine/

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THANK YOU