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Kursk State Medical University
Department of Histology, Embryology, Cytology




HIPPOCAMPUS
                           Student: A.H. Borzacchini
                            Supervisor: T.A. Ishunina
              Kursk-2012
Hippocampus
      • Is a neural structure in the
        medial temporal lobe of the
        brain that has a distinctive,
        curved shape which
        resembles a shape of a
        seahorse.
      • It belongs to the limbic
        system and plays important
        roles in the consolidation of
        information from short-
        therm memory to long-
        therm memory and spatial
        navigation.
      • Humans and other
        mammals have two
        hippocampi, one in each
        side of the brain.
Hippocampal Cells and Layers
• The hippocampus is composed of multiple subfields:

  • Cornu Ammonis (CA)
     •   CA1
     •   CA2
     •   CA3
     •   CA4


  • Dentate Gyrus
     • Fascia Dentata
     • Hilus (region CA4)
Nissl-stained coronal section of the brain of a monkey, showing hippocampus (circled).
Hippocampus Regions
Drawing of Hippocampus by Camilo Golgi
Subregions of the hippocampus exhibit histologial differences.
CA regions and their layers
• 1) Alveus
  • Deepest layer
  • Contains axons from pyramidal layer, passing toward to the fornix
    (fimbria)
  • One of the major outputs of the hippocampus

• 2) Stratum Oriens
  • Next superficial layer
  • Contains cell bodies of inhibitory basket cells and horizontal
    trilaminar cells (their axons innervate 3 layers: oriens, pyramidal
    and radiatum)
  • Also contains basal dendrites of pyramidal neurons, where they
    receive input from others pyramidal cells, septal fibers and
    commissural fibers from the colateral hippocampus (especially in
    CA3 and CA2)
• 3) Stratum Pyramidale
  • One of the more visible strata to the naked eye
  • Contains the cell bodies of the pyramidal neurons, which are the
    principal excitatory neurons of the hippocampus
  • In CA3 region, this stratum contains synapses from the mossy fibers,
    cell bodies of many interneurons, including axo-axonic cells,
    bistratified cells, and radial trilaminar cells

• 4) Stratum Lucidum
  • Only found in CA3 region
  • One of the thinnest strata of hippocampus
  • Contains the mossy fibers from the dentate gyrus and granule cells

• 5) Stratum Radiatum
  • Contains septal and commissural fibers, Schaffer collateral fibers (are
    an integral part of memory formation and the emotional network
    and they have the projection forward from CA3 to CA1)
  • Some interneurons can be found here, basket cells, bistratified cells,
    and radial trilaminar cells
• 6) Stratum Lacunosum
  • Thin stratum that is often grouped togehter wiht stratum
    moleculare (stratum lacunosum-moleculare)
  • Contains Schaffer colateral fibers and perforant path fibers from
    the superficial layers of the entorhinal cortex


• 7) Stratum Moleculare
  • Most superficial layer
  • Perforant path fibers form synapses onto the distal, apical
    dendrites of pyramidal cells


• Hippocampal sulcus
  • Cell-free region that separates the CA1 region from the dentate
    gyrus
  • The sulcus is often used as a fixed reference point for recording
    electroencephalography (EEG), bacause the phase of recorded
    theta rhythm varies systematically through the strata.
CA Regions
• Region CA4
  • Also called Hilus (when considered part of the dentate
    gyrus)
  • Contains mossy cells – receive inputs from granule cells
    located nearby in the dentate gyrus in the form of mossy
    fibers
  • Receive a small number of connections from pyramidal cells
    located in CA3, and in turn, project back into the dentate
    gyrus at distant septotemporal levels.
Region CA4
Human hippocampus shows: - granular neuron (blue, diamond)
                          - protoplasmic astrocyte (brown, asteristic)
SG= stratum granulosum
Scale E= 20µm
Region CA4
SP= stratum pyramidale
SM= stratum moleculare
SG=stratum granulosum
Scale A= 500µm
• Region CA3
  • Receives input along the mossy fibers from granule cells in the DG
    and from projections cells in entorhinal cortex along the perforant
    path
  • Pyramidal cells (approximately 200,000 in each hemisphere in rats)
    send some axons back to the hilus, but the majority project to
    regions CA2 and CA1 (a pathway called the Schaffer collaterals)
  • Divided into 3 divisions:
     • CA3a – part of the cell band which is most distal from the DG and closest
       to CA1
     • CA3b – middle part of the band nearest to the fornix connection
     • CA3c- most proximal to the DG, inserting into hilus
  • Is considered to be the “pacemaker” of the hippocampus, much of
    the synchronous bursing activity associated with interictaleptiform
    activity apperars to be generated, the excitatory collateral
    interconnectivity is responsible for this
  • Has pyramidal axon collateralsramifying extensively with local region
    and making excitatory contacts with neighbors
  • CA3 has been implicated in a number of working theories on
    memory and learning hippocampal processes; sharp EEG waves also
    implicated in memory consolidation.
• Region CA2
  • Small region located between CA1 and CA3
  • Receive perforant path input entorhinal cortex, but do not
    receive mossy fiber connections from DG
  • Pyramidal cells are more similar to those of CA3 than those of
    CA1, so it is grouped as a separate region
  • Has a high resistance to epileptic damage


• Region CA1
  • First region that yields a significant output pathway
  • Sends significant output foward to the subiculum
  • Like CA3, receives input from superficial entorhinal cortex along
    perforant pathway, but unlike CA3, contains vey few recurrent
    connections (in rats, CA1 contains approximately 250,000
    pyramidal cells)
     • Subiculum (“support”): most inferior component of the hippocampal
       fomation, lies between the entorhinal cortex and the CA1 region.
Basic Circuit of Hippocampus
Dentate Gyrus
• Is composed of a similar series of strata:
  • Polymorphic layer: -most superficial
                        -contains many interneurons, and the axons of
  the dentate granules cells pass through this stratum on the way to
  CA3.
  • Stratum Granulosum: -contains the cell bodies of the dentate
    granule cells
  • Stratum Moleculare, inner 1/3: -is where both commissural
    fibers from the contralateral DG run and form synapses as well as
    where the inputs from the medial septum terminate, both on the
    proximal dendrites of the granule cells.
  • Stratum Moleculare, external 2/3: -deepest strata
                                       -perforant path fibers run
    through, making excitatory synapses onto the distal apical
    dendrites of the granile cells.
• Fascia Dentata:

  • Is the earliest stage of the hippocampal circuit
  • Its primary input is the perforant path from the superficial layers
    of the entorhinal cortex
  • Its principal neurons are tiny granule cells which give rise to
    unmyelinated axons called mossy fibers which project to the hilus
    and CA3.
  • Receives feedback connections from mossy cells in the hilus at
    distant levels in the septal and temporal directions
  • The Fascia Denata and the Hilus together make up the Dentate
    Gyrus, as with all regions of the hippocampus, the DG also receive
    GABAergic and cholinergic input from the medial septum and the
    diagonal band of Broca.
Schematic showing regions of the hippocampus proper in relation to other structures.
Ultramicroscopy: 3-D visualization of neuronal networks in the
                         mouse brain
Pyramidal cell dendritic trees of population of CA1 neurons in isolated
hippocampi
“Brainbow” transgenic mouse hippocampus (40x)
2008 Small World Competition – 18th place
Photographer Dr. Tamily Weissman, Department of molecular and cellular Biology, Harvard University
Technique: confocal
References
• “Opera Omnia”, volume II – Camillo Golgi
• Histology of the Central Nervous System – Michael Hortsch,
  Ph.D (University of Michigan)
• Functional Histology 2e – Prof. Jeffrey Kerr
• Histology-World – Floris G. Wouterlood, Ph.D
• Department of Bioelectronics, Institute of Solid State
  Electronics, TU Vienna, Austria - H.U. Dodt , N. J ährling, S.
  Saghafi, K. Becker
• "Ch 3. Hippocampal Neuroanatomy“ in The Hippocampus
  Book - Andersen P, Morris R, Amaral D, Bliss T, O'Keefe J.
  (Oxford University)
•Thank you for your
    Attention!!!

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Hippocampus

  • 1. Kursk State Medical University Department of Histology, Embryology, Cytology HIPPOCAMPUS Student: A.H. Borzacchini Supervisor: T.A. Ishunina Kursk-2012
  • 2. Hippocampus • Is a neural structure in the medial temporal lobe of the brain that has a distinctive, curved shape which resembles a shape of a seahorse. • It belongs to the limbic system and plays important roles in the consolidation of information from short- therm memory to long- therm memory and spatial navigation. • Humans and other mammals have two hippocampi, one in each side of the brain.
  • 3.
  • 4. Hippocampal Cells and Layers • The hippocampus is composed of multiple subfields: • Cornu Ammonis (CA) • CA1 • CA2 • CA3 • CA4 • Dentate Gyrus • Fascia Dentata • Hilus (region CA4)
  • 5. Nissl-stained coronal section of the brain of a monkey, showing hippocampus (circled).
  • 7. Drawing of Hippocampus by Camilo Golgi Subregions of the hippocampus exhibit histologial differences.
  • 8. CA regions and their layers • 1) Alveus • Deepest layer • Contains axons from pyramidal layer, passing toward to the fornix (fimbria) • One of the major outputs of the hippocampus • 2) Stratum Oriens • Next superficial layer • Contains cell bodies of inhibitory basket cells and horizontal trilaminar cells (their axons innervate 3 layers: oriens, pyramidal and radiatum) • Also contains basal dendrites of pyramidal neurons, where they receive input from others pyramidal cells, septal fibers and commissural fibers from the colateral hippocampus (especially in CA3 and CA2)
  • 9. • 3) Stratum Pyramidale • One of the more visible strata to the naked eye • Contains the cell bodies of the pyramidal neurons, which are the principal excitatory neurons of the hippocampus • In CA3 region, this stratum contains synapses from the mossy fibers, cell bodies of many interneurons, including axo-axonic cells, bistratified cells, and radial trilaminar cells • 4) Stratum Lucidum • Only found in CA3 region • One of the thinnest strata of hippocampus • Contains the mossy fibers from the dentate gyrus and granule cells • 5) Stratum Radiatum • Contains septal and commissural fibers, Schaffer collateral fibers (are an integral part of memory formation and the emotional network and they have the projection forward from CA3 to CA1) • Some interneurons can be found here, basket cells, bistratified cells, and radial trilaminar cells
  • 10. • 6) Stratum Lacunosum • Thin stratum that is often grouped togehter wiht stratum moleculare (stratum lacunosum-moleculare) • Contains Schaffer colateral fibers and perforant path fibers from the superficial layers of the entorhinal cortex • 7) Stratum Moleculare • Most superficial layer • Perforant path fibers form synapses onto the distal, apical dendrites of pyramidal cells • Hippocampal sulcus • Cell-free region that separates the CA1 region from the dentate gyrus • The sulcus is often used as a fixed reference point for recording electroencephalography (EEG), bacause the phase of recorded theta rhythm varies systematically through the strata.
  • 11.
  • 12.
  • 13. CA Regions • Region CA4 • Also called Hilus (when considered part of the dentate gyrus) • Contains mossy cells – receive inputs from granule cells located nearby in the dentate gyrus in the form of mossy fibers • Receive a small number of connections from pyramidal cells located in CA3, and in turn, project back into the dentate gyrus at distant septotemporal levels.
  • 14. Region CA4 Human hippocampus shows: - granular neuron (blue, diamond) - protoplasmic astrocyte (brown, asteristic) SG= stratum granulosum Scale E= 20µm
  • 15. Region CA4 SP= stratum pyramidale SM= stratum moleculare SG=stratum granulosum Scale A= 500µm
  • 16. • Region CA3 • Receives input along the mossy fibers from granule cells in the DG and from projections cells in entorhinal cortex along the perforant path • Pyramidal cells (approximately 200,000 in each hemisphere in rats) send some axons back to the hilus, but the majority project to regions CA2 and CA1 (a pathway called the Schaffer collaterals) • Divided into 3 divisions: • CA3a – part of the cell band which is most distal from the DG and closest to CA1 • CA3b – middle part of the band nearest to the fornix connection • CA3c- most proximal to the DG, inserting into hilus • Is considered to be the “pacemaker” of the hippocampus, much of the synchronous bursing activity associated with interictaleptiform activity apperars to be generated, the excitatory collateral interconnectivity is responsible for this • Has pyramidal axon collateralsramifying extensively with local region and making excitatory contacts with neighbors • CA3 has been implicated in a number of working theories on memory and learning hippocampal processes; sharp EEG waves also implicated in memory consolidation.
  • 17. • Region CA2 • Small region located between CA1 and CA3 • Receive perforant path input entorhinal cortex, but do not receive mossy fiber connections from DG • Pyramidal cells are more similar to those of CA3 than those of CA1, so it is grouped as a separate region • Has a high resistance to epileptic damage • Region CA1 • First region that yields a significant output pathway • Sends significant output foward to the subiculum • Like CA3, receives input from superficial entorhinal cortex along perforant pathway, but unlike CA3, contains vey few recurrent connections (in rats, CA1 contains approximately 250,000 pyramidal cells) • Subiculum (“support”): most inferior component of the hippocampal fomation, lies between the entorhinal cortex and the CA1 region.
  • 18. Basic Circuit of Hippocampus
  • 19. Dentate Gyrus • Is composed of a similar series of strata: • Polymorphic layer: -most superficial -contains many interneurons, and the axons of the dentate granules cells pass through this stratum on the way to CA3. • Stratum Granulosum: -contains the cell bodies of the dentate granule cells • Stratum Moleculare, inner 1/3: -is where both commissural fibers from the contralateral DG run and form synapses as well as where the inputs from the medial septum terminate, both on the proximal dendrites of the granule cells. • Stratum Moleculare, external 2/3: -deepest strata -perforant path fibers run through, making excitatory synapses onto the distal apical dendrites of the granile cells.
  • 20.
  • 21. • Fascia Dentata: • Is the earliest stage of the hippocampal circuit • Its primary input is the perforant path from the superficial layers of the entorhinal cortex • Its principal neurons are tiny granule cells which give rise to unmyelinated axons called mossy fibers which project to the hilus and CA3. • Receives feedback connections from mossy cells in the hilus at distant levels in the septal and temporal directions • The Fascia Denata and the Hilus together make up the Dentate Gyrus, as with all regions of the hippocampus, the DG also receive GABAergic and cholinergic input from the medial septum and the diagonal band of Broca.
  • 22. Schematic showing regions of the hippocampus proper in relation to other structures.
  • 23. Ultramicroscopy: 3-D visualization of neuronal networks in the mouse brain Pyramidal cell dendritic trees of population of CA1 neurons in isolated hippocampi
  • 24. “Brainbow” transgenic mouse hippocampus (40x) 2008 Small World Competition – 18th place Photographer Dr. Tamily Weissman, Department of molecular and cellular Biology, Harvard University Technique: confocal
  • 25. References • “Opera Omnia”, volume II – Camillo Golgi • Histology of the Central Nervous System – Michael Hortsch, Ph.D (University of Michigan) • Functional Histology 2e – Prof. Jeffrey Kerr • Histology-World – Floris G. Wouterlood, Ph.D • Department of Bioelectronics, Institute of Solid State Electronics, TU Vienna, Austria - H.U. Dodt , N. J ährling, S. Saghafi, K. Becker • "Ch 3. Hippocampal Neuroanatomy“ in The Hippocampus Book - Andersen P, Morris R, Amaral D, Bliss T, O'Keefe J. (Oxford University)
  • 26. •Thank you for your Attention!!!