Kursk State Medical UniversityDepartment of Histology, Embryology, Cytology

HIPPOCAMPUSStudent: A.H. BorzacchiniSupervisor: 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 GolgiSubregions 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 granulosumScale E= 20µm

Region CA4SP= stratum pyramidaleSM= stratum moleculareSG=stratum granulosumScale 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 placePhotographer Dr. Tamily Weissman, Department of molecular and cellular Biology, Harvard UniversityTechnique: 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!!!