From NeuralNetoff

Contents 1 3-Dimensional Considerations of Hippocampus Architecture 2 Covering the Basics 3 The Trisynaptic Circuit 4 Perforant Pathway (PP) 5 Dentate Gyrus (DG) 6 Mossy Fibers of DG 6.1 Associational Projections of DG 7 Hippocampus Proper 8 CA3/2 9 CA1 and Subicular Complex 9.1 Links and references

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.

    

As seen above, the complexity of hippocampus anatomy is not fully appreciated in 2D (left) as compared to its 3D properties (right).</p>

Covering the Basics

In hippocampal literature, there are two axes that are commonly used to describe the spatial layout of the structure:

• Septotempal
• Transverse

In general, there are four gross regions of the hippocampus (see figure below):

1. Dentate Gyrus (DG)
2. Hippocampus proper:
• CA1–3
3. Subicular complex:
• Subiculum (Sb)
• Presubiculum (PrS)
• Parasubiculum (PaS)
4. Entorhinal cortex (EC):
• Medial (MEC)
• Lateral (LEC)

R. Cajal, (1911).

There are 2 major input/outputs of the hippocampus:

1. Perforant path
2. Alveus/Fimbria/Fornix

Below, we see that the hippocampus receives and projects to the contralateral hippocampus via an extension of the fornix known as the fimbria.

H. Gray, (1918).

Before examining the details of hippocampus anatomy it is important to consider its neuronal magnitude as illustrated in the figure below.
M. B. MacIver, (2005).

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.

In this wiki, we will explore the anatomy of the trisynaptic circuit by the individual pathways paired with the structures which give rise to them as well as the regions innervated by the pathways.

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):

1. Molecular: axons of the PP terminate here.
2. Granular: comprised of principle cells (granular) which give rise to the mossy fibers of the DG.
3. 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).

The projections of the MFs are mainly organized in a lamellar fashion and are oriented transversely with minimal overlap. At septal levels, however, lamellar organization breaks down. Here, MFs turn to travel parallel with the septotemporal axis for approximately 2mm before terminating.

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).

* Note that the interneurons (blue) of the polymorphic layer project back to granular cells (red) laterally. This lateral distribution is well suited to promote the integration of information along septotemporal axis of DG.

Hippocampus Proper

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.

Apical level-mainly acellular.

• 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.

CA3/2

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:

1. Commissural fibers: innervates the contralateral hippocampus.
2. 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.

* The bodies of three CA3 cells and their projection fields (matched by color) are shown here at septal, mid, and temporal levels. In addition to having projections to CA1 fields of the same septotemporal level, CA3 cells project laterally. However, lateral projections are preferential depending upon where along the septotemporal plane the axon originates. Notice the blue cell has its heaviest projections at mid and septal levels while the green cell has its heaviest projections at mid and temporal levels.

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.

Coming full circle from the trisynaptic circuit, both the presubiculum and parasubiculum project to the EC (layers III and II, respectively).

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.

The Hippocampus is a structure in the temporal lobe of the brain.

J. Anat. (2005) 207 , pp35–66
Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory

Layers of the hippocampus

Ramon y Cajal camera lucida drawing of the hippocampus:

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