The Entorhinal cortex, Grid &
AG I. Vida & AG D. Schmitz
• Entorhinal cortex – Location & Morphology,
Cell types in different layers
• Grid & place cells – Brief introduction
• EC or the brodman area 28. Lateral area – 28a &
medial area 28b
• Nodal point between hippocampal formation &
association with the cortex
• Medial subdivision cells are spatially modulated
but absent in LEC. LEC convey olfactory &
• Anteriorly, the EC meets with olfactory &
amygdaloid cortices & medially it merges with the
structures belonging to the hippocampal
formation. Laterally it meets the perirhinal cortex.
a: Ramon Y Cajal
b: Cathrin B. Canto et al: What does the anatomical organization of the entorhinal
cortex tell us?: Neural plasticity (2008)
• Horizontal cells & Multipolar neurons (MPNs).
• MPN are abundant & non- or sparsely spiny.
• Positive for Calretinin (CR) & GABA
• Diameter of dendritic tree varies between 100 um to 150
• Axons of layer I neurons travel towards layer II & layer III
• Horizontal cells present between layers I & II. Spherical to
elongated soma of 13 – 15 μm.
• Spine free dendrites.
• Are GABAergic in LEC and dendritic terminal in MEC stains
positive for cholecystokinin
• Densely packed, large & medium sized pyramidal
& stellate cells.
• Abundant cell type & more common in MEC.
• Soma is variable, but characteristic spiny dendritic
• Dendritic arbor has multiple, roughly equally sized
primary dendrites branching widely.
• Thick axon. Gives very thin collaterals, branching
repeatedly & reaching superficial layers & colocalizing with entire dendritic tree.
• Excitatory using glutamate for transmission & stain
• Common in LEC.
• Large polygonal soma, with spiny primary
dendrites mostly in horizontal & ascending
• Differs from stellate cells in MEC as fan cells have
small descending dendrites.
• Medium sized triangular or ovoid shaped soma.
• Located in deep portion of layer II.
• Spiny thick apical dendrite. Basal dendrites are
spiny, thin, short & straight with extensive
2010: Prateep Beed: Micro circuitry in the
• Smooth & thin axons, giving off collaterals &
distributing in layers I-III.
• Subtype of pyramidal –like cells known as
horizontal pyramidal cell located in superficial part
of layer II.
• Another subtype has thick & sparsely or nonspiny
apical dendrite branching in layer II.
• MPNs, bipolar, basket & chandelier cells.
MPNs - polygonal, fusiform or round cell bodies with
multiple spiny dendrites reaching layer I and deep
into layer III. Axons travel to layer II.
• Bipolar cells – Soma located in layer II and border to
layer I. Dendrites orient horizontally. Vertical bipolar
cells have spindle shaped soma with one ascending &
one descending primary dendrite & branch into thinner
• Fast spiking basket –like cells – small spherical soma,
sparsely spiny dendrites projecting to layer I. Axon
confined to layer II and form basket –like complex
around soma of other cells. Basket cells in whole EC
• Chandelier cells – vertical aggregations of axonal
boutons called candles. Medium sized & variable
shaped soma. Nonspiny, poorly ramyfying dendrites
stays within layer II/III. Vertically oriented axonal tree.
GABAergic, PV – positive cells.
• Spiny & non-spiny pyramidal cells
SPINY PYRAMIDAL CELLS (SPCs)
• Present in the LEC.
• Somata gives rise to prominent apical dendrite
that bifurcates, becomes spiny & branches. Axon
projects towards the subiculum.
NONSPINY PYRAMIDAL CELLS (NSPCs)
• Triangular to spherical shaped somata.
• Non spiny apical dendrite branches closer to soma
& also branches in superficial layers.
• Somata are elongated, polygonal or spherical.
• Spiny dendrites and dendrites branching in layer I.
• Axons forms collaterals in layer III.
PRINCIPAL MPN SOMATA
• Small & Spherical. Largest located in outer half of layer III.
• Cell body is 15-18 um with spiny dendrites branching in all
directions. Axons reach the hippocampus.
INTERNEURONS RESEMBLING PYRAMIDAL CELLS
• Pyramidal looking interneurons (PLI). Also known as type
3-(Gloveli) or type 1-(Kumar) cells.
• Pyramidal shaped cell body & non spiny basal & apical
dendrites. Dendrites collateral through layer II reaching
layer I. Axons extend into layer III.
2010: Prateep Beed: Micro circuitry in the
• Pyramidal shaped neurons border to layer III &
• Similar properties of layer III & layer V pyramidal
• Also present are Bipolar cells.
• Dendrites grow horizontally and axons collaterals
travel towards superficial layer III & deep layers.
• No difference between MEC & LEC principal cells.
• Located below the layer IV.
• Soma varies from pyramidal form to star shaped.
• Large and spiny apical dendrite branching close to the
soma. Spine occurs after the first or second
• Small pyramidal cells have more basal dendrites &
densely occupied with spines. Main axon reaches out
to the dentate gyrus.
• Soma is polygonal. Sparsely spiny apical dendrite
branching in layer I. In MEC, primary dendrite is
• Axons branches into layer V & VI.
• Soma varies from spherical to pyramidal.
• Multipolar spiny dendrites. Axon branches within
layer V but reaches out to subiculum via the dentate
• Spindle like soma.
• Dendrites are spiny and extend from the soma to the
subiculum unidirectional & extensive branching in
layer I & II. Axons reaches the dentate gyrus.
• Soma branches within layer III – V. Axons projects
towards layer V.
• MPNs are present throughout layer VI. Have
spherical soma & spiny dendrites. Axon reaches
• Also present are classical pyramidal cells. Soma
are medium sized. Dominant dendrites descend
towards the subiculum. Axons branches at
Navigation & the Hippocampus
• Hippocampus function is based on two discoveries:
- Amnestic consequence as a removal of hippocampus
- Spiking activity of hippocampal neuron with spatial
• Navigation is based on two mechanisms:
- Map based or Allocentric navigation
- Integration of motion & knowledge of previous positions
• Navigation guiding involves the hippocampus &
the entorhinal cortex.
• Neural system for navigation should have the
capacity to store large quantities
• Episodic memory is the memory of our
experiences. Relevant to recent & remote events.
Also known as Implicit memory.
• Semantic memory is more structural record of
facts, meanings, concept & knowledge. Similar to
allocentric map which defines a location largely
independent of how the animal got there.
• Semantic memory is derived from episodic
memory and we learn new facts or concepts from
our experiences & episodic memory supports the
• Semantic memory depends on the hippocampal –
• Still debatable if semantic acquired information
becomes hippocampus independent or
hippocampus dependent forever.
• Animal’s spatial coordinates are encoded by
striking firing patterns from hippocampal “place
cells” & entorhinal “grid cells”.
• Present throughout the MEC & in the pre - &
parasubiculum. Abundant in layer 2 of MEC.
• Arranged along the dorsal to ventral axis of the MEC.
• Small grid scales present in dorsal part & large grid scales
present in large parts.
• Deep layers are intermingled with head directional cells.
• Grid cell provides a neural representation of space and head
directional cells provide a directional reference frame.
• These cells are active in all environment & behave in a
a & b: Buzsaki & Moser: Memory, navigation & theta rhytm in hippocampal – entorhinal system.
Nature neuroscience review (2013)
c: Burgess et al: Evidence for grid cells in a human memory network. Nature (2010)
• Place cells are the basic elements of a distributed
noncentered map-like representation. (O’Keefe &
Nadel – 1978).
• Abundant in the Hippocampus.
• Place cell provides the animal with a dynamic and
continuously updated representation of
allocentric space and its own position in that
• Fire selectively when an animal occupies a
• They fire differentially in different environment.
• After hippocampal damage rats are terrible at
spatial problem solving & appear lost in space.
a: Buzsaki & Moser: Memory, navigation & theta rhytm in hippocampal – entorhinal system. Nature
neuroscience review (2013)
b: Burgess et al: Evidence for grid cells in a human memory network. Nature (2010)
c: The Knierim Lab (John Hopkins university)
• Hippocampal place cells behave as a navigator.
Updates estimate of location using dead
reckoning & sightings.
• Grid cells provide the path integration input.
Vielen Dank. Wishing everyone a merry christmas and a happy new year