3-Dimensional Considerations of Hippocampus Architecture
Although the anatomy and connectivity of the hippocampus is well presented 2-dimensionally, it is vital to consider its 3-dimensional architecture in the realm of hippocampal research.
Covering the Basics
In hippocampal literature, there are two axes that are commonly used to describe the spatial layout of the structure:
In general, there are four gross regions of the hippocampus (see figure below):
- Dentate Gyrus (DG)
- Hippocampus proper:
- Subiculum (Sb)
- Presubiculum (PrS)
- Parasubiculum (PaS)
- Medial (MEC)
- Lateral (LEC)
There are 2 major input/outputs of the hippocampus:
- Perforant path
Below, we see that the hippocampus receives and projects to the contralateral hippocampus via an extension of the fornix known as the fimbria.
The Trisynaptic Circuit
When cut in the transverse plane, the hippocampus exhibits a set of three interconnected afferent pathways known as the trisynaptic circuit. Below is a schematic representing the major structures and names of the pathways involved in this circuit.
Perforant Pathway (PP)
The PP originates from layer II of the EC and projects to the supra/infra-pyramidal portions of the DG. It also sends a longer projection to CA3 which directly innervates the principle cells (pyramidal) of CA3 .
From the EC, PP fibers travel dorsally and bend sharply into the transverse plane. They cross the hippocampus fissure at the level of the crest of the DG. From here, the fibers bifurcate and run along the supra/infra-pyramidal blades of the DG and terminate on the principle cells (granular) of the DG. These projections are divergent in nature; the PP gives off collateral processes which innervate distant septotemporal levels of the DG. However, there is also convergence in the sense that EC neurons have overlapping projections in the DG.
The EC also gives rise to axons which innervate the molecular layers of the S (perforating the pyramidal layer along its septotemporal axis) and CA1 as seen in the figure above (top dotted blue line of the shaded region). These projections originate in layer III of the EC. The EC receives projections back from these two areas (S and CA1) which terminate in layer V. An example of a digitally reconstructed principle cell (stellate) of the EC is shown here:
Dentate Gyrus (DG)
The DG is composed of three layers (see figure below):
- Molecular: axons of the PP terminate here.
- Granular: comprised of principle cells (granular) which give rise to the mossy fibers of the DG.
- Polymorphic: supplies associated connections within the DG
Mossy Fibers of DG
The second pathway examined here in the trisynaptic circuit originates from the granular cells DG. Below is a pair of examples of digitally reconstructed granular cells:
The mossy fibers (MF) of granular cells directly innervate the pyramidal cells of the CA3. However, before reaching their final destination they give off collaterals innervating interneurons of the polymorphic layer (DG) which feedback to the granular cells. These associated projections are considered in more detail later.
The axons of the MF pathway synapse on thorny excrescences of CA3 pyramidal cells at the level of the stratum lucidum (superficial to pyramidal layer CA3). One MF can make up to 30-40 synapses on a single excrescence. Both convergence and divergence is observed in this pathway. That is, one pyramidal neuron is innervated by approximately 70 granular cells (convergence). In contrast, one granular cell typically innervates 15 different pyramidal cells (divergence).
Associational Projections of DG
As mentioned above, collaterals from MFs innervate the interneurons found in the polymorphic layer of the DG. In turn, these interneurons project back to the apical dendrites of granular cells. This feedback loop is divergent and distributed laterally along the septotemporal axis (see schematic below).
The hippocampus proper is comprised of several layers (see figure below):
Basal level-granular cells found here.
- Alveus: most superficial layer and contains commissural fibers of pyramidal cells via the fimbria.
- Stratum Oriens: contains inhibitory basket cells and the basal dendrites of pyramidal neurons (innervated by recurrent collaterals and contralateral hippocampus). The recurrent connections found in this layer are the source of the high divergency found in the circuitry of the hippocampus proper.
- Stratum Pyramidale: contains the somas of pyramidal neurons. MFs also synapse in this layer.
- Stratum Lucidum: MFs transverse and terminate in this region.
- Stratum Radiatum: contains the Schaffer Collaterals of CA3-1 pathway.
- Stratum Lacunosum-Moleculare: also contains some fibers from the Schaffer Collaterals. In CA1, PP fibers are found here and synapse on distal apical dendrites of pyramidal cells.
Apical level-mainly acellular.
It is important to understand that the hippocampus proper can be separated into three distinct regions (CA1-3). However, here CA3 and CA2 anatomy are present in composite style in the interest of clarity.
The major input of CA3 are the MFs of the DG (see above text for details). There are two major outputs of the CA3 (see figure below:
- Commissural fibers: innervates the contralateral hippocampus.
- Schaffer Collaterals (SfC): innervates pyramidal cells of CA1.
The 3-dimensional distribution of the SfC pathway is more complex than what is typically represented in 2D (digitally reconstructed pyramidal cells shown above). The axonal distribution of SfC fibers differ along the transverse axis:
- At septal levels, axons project to neighboring CA1 fields deeply in stratum radiatum/oriens.
- At temporal levels, axons project to distal (bordering S) CA1 fields at more superficial levels in the stratum radiatum.
Furthermore, axonal distribution also differ along the septotemporal axis:
- Pyramidal cells near the DG project further and more heavily in septal direction.
- Pyramidal cells near CA1 project further and more heavily in temporal direction.
Finally, CA3 pyramidal cells along transverse axis give rise to axons which preferentially innervate different septotemporal levels of CA1 in a gradient fashion. Below is an example of these distribution properties of CA3.
CA1 and Subicular Complex
As detailed above, the dominant input CA1 comes from CA3 via the schaffer collaterals. The CA1 projects to each region of the subicular complex (subiculum, presubiculum, and parasubiculum). Projections to the S are made in a columnar fashion. In addition to subicular projections, CA1 also innervates the EC.
Below are some examples of digitally reconstructed pyramidal cells of the CA1.
Below you find some more supporting figures and diagrams of the hippocampus. <p>
Links and references
- All digitally reconstructed neurons were taken from the online database http://neuromorpho.org/neuroMorpho/.
- D. G. Amaral and M. P. Witter. (1989). Neuroscience. 31 (3), 571-591.
- M. P. Witter and E. I. Moser. (2006). TINS. 29 (12), 671-678.
Interneurons of the Hippocampus
HIPPOGIMPUS 6.347-470 (1996)
The Role of the Subiculum in Epilepsy and Epileptogenesis A, Schematic of a transverse section of the hippocampus and parahippocampal region. The subiculum occupies a central position between hippocampus proper and parahippocampal structures. Entorhinal cortex layers are identified with Roman numerals. DG, dentate gyrus; CA, cornu ammonis.
The Role of the Subiculum in Epilepsy and Epileptogenesis
B, Selected connections between hippocampal and parahippocampal regions. Note that hippocampal areas (three-layered cortex) tend to project unidirectionally, whereas parahippocampal areas (four or more layers) project to multiple targets. Dashed line from subiculum to CA1 indicates one possible mechanism of epilepsy-induced plasticity, whereby excitatory connections between these two areas may be strengthened
J. Anat. (2005) 207 , pp271–282
The subiculum: what it does, what it might do, and what neuroanatomy has yet to tell us