Anatomy

From www.temporal-lobe.com

Here, a short description of all anatomical subdivisions of the rat hippocampal-parahippocampal region and retrosplenial cortex is provided. For an extensive description, see ^[1], ^[2], ^[3].

Contents 1 Hippocampal Formation (HF) 2 Parahippocampal Region (PHR) 3 Retrosplenial cortex (RSC) 4 Nomenclature 5 References

Hippocampal Formation (HF)

The rat HF is a C-shaped structure that is situated in the caudal part of the brain. The cortex that forms the HF has a three-layered appearance. A deep layer, comprising a mixture of afferent and efferent fibers and interneurons. Superficial to this polymorph layer is the cell layer, which is composed of principal cells and interneurons. On top, the most superficial layer is situated - this layer is referred to as the molecular layer (stratum moleculare) in the DG and the Sub. In the CA-region, the molecular layer is subdivided into a number of sub-layers. In the CA3, three sub-layers are distinguished: The stratum lucidum, representing the input from the DG, stratum radiatum, i.e the apical dendrites of the neurons in stratum pyramidale and most superficially, the stratum lacunosum-moleculare comprising the apical tufts of the apical dendrites. The lamination in the CA2 and the CA1 is similar with the exception that the stratum lucidum is missing (see Figure 1 in our NRN Review)

Dentate Gyrus (DG)

The DG is a "V" shaped structure situated in the most proximal part of the HF. DG is subdivided into the crest area, the enclosed blade, positioned adjacent to CA1 and the exposed blade and within each subregion three layers can be distinguished. In the molecular layer (stratum moleculare), an inner, middle and outer one-third is discerned, based on afferent connections impinging on the dendrites of the granule cells. The somas of the granule cells are situated in the granular cell layer (stratum granulare). The hilus or polymorphic layer (stratum multiforme) is enclosed by the granule cell layer and contains a rich variety of cell types including mossy cells.

Cornu Ammonis (CA)

The CA subfield forms the area between DG and Sub. The laminar organization of CA3, CA2 and CA1 is rather similar. The principle cell layer (stratum pyramidale) consists of the somas of the pyramidal cells. The stratum oriens is located deep to the stratum pyramidale and contains the basal dendrites of the pyramidal cells. The apical dendrites of the pyramidal cells stretch into the stratum radiatum and the stratum lacunosum moleculare. An additional layer, the stratum lucidum, is located only in CA3 just superficial to the stratum pyramidale. The term CA4, in between the hilus and CA3 is avoided. A separate description of CA2 is not included since this is a small and under-investigated region in the rat.

Subiculum (Sub)

The Sub stretches between CA1 and the PrS. It consists of a polymorphic layer (not depicted in the diagram), a stratum moleculare and a broad principle cell layer with large pyramidal cells, together with a mixture of smaller interneurons. The stratum moleculare of the subiculum can be subdivided into a deeper portion that is continuous with the stratum radiatum of CA1 and a superficial portion that is continuous with the stratum moleculare of the PrS and stratum lacunosum moleculare of CA1. The stratum pyramidale can be divided into a deep and a superficial part. A transitional area between CA1 and the Sub, termed prosubiculum, has been distinguished by several authors. In this region, the stratum radiatum becomes gradually smaller and the stratum pyramidale broadens. The contemporary view regards the prosubiculum as the area where CA1 and Sub neurons overlap.

Parahippocampal Region (PHR)

The PHR lies adjacent to the HF (bordering with the subiculum) and is characterized by an increase in the number of cell layers as compared with the HF. At the junction with the subiculum, superficially positioned cell layers become apparent and a cell-free zone called lamina dissecans exists in-between the two main neuronal sheets. The PHR is generally described as having six layers. The PHR is divided into five sub-regions: the presubiculum (PrS), parasubiculum (PaS), entorhinal cortex (EC), perirhinal cortex (PER) and postrhinal cortex (POR). The coordinate systems that define the position within the HF and PHR are explained in Figure 1 (NRN Review).

Presubiculum (PrS) and Parasubiculum (PaS)

The PrS is located distally from the HF and is positioned in between the Sub and the PaS. The PrS is distinguished from the Sub by a densely packed superficial pyramidal cell layer (II/III). Similar to the EC, the PrS has a plexiform layer, lamina dissecans (IV), and two deep layers with pyramidal cells. The term postsubiculum was introduced by Brodmann to identify the dorsal part of the PrS. Some controversy remains about the existence of this area. In this diagram, the postsubiculum is considered as the septal (dorsal) part of the PrS. The PaS lies distal to the PrS. Layer II and III have densely packed pyramidal cells and the deep layers are continuous with the deep layers of EC.

Entorhinal Cortex (EC)

The EC forms the ventroposterior part of the rat cerebral hemisphere and is bordered medially largely by the PaS and dorsolaterally by the POR and PER. The EC consists of six layers, four cell layers (II, III, V and VI) and two plexiform layers (I, IV or lamina dissecans). Two subdivisions are generally recognized; a medial (MEA) and a lateral part (LEA). For more information, see the EC article on scholarpedia.

Perirhinal (PER) and Postrhinal (POR) cortex

The PER and POR are situated dorsally along the rhinal fissure. Both consist of six cell layers. The PER consist of two subdivisions, the agranular area 35 (A35) and the dysgranular area 36 (A36) or ectorhinal cortex. POR consists of a ventral agranular and dorsal (dys)granular region. The rostral border of POR with PER is difficult to discern. The ventral part of POR is quite similar to A35, but the presence of ectopic layer II cells makes it possible to discriminate the region. In the PER and POR, layer IV is variably developed.

Below is Figure 1 of the Nature Reviews Neuroscience Review in which each subregion of the hippocampal formation and the parahippocampal region are visualized.

Nature Rightslink License Number: 2376551098486

A | Lateral (left panel) and caudal (right panel) views. For orientation in the hippocampal formation (consisting of the dentate gyrus (DG; dark brown), CA3 (medium brown), CA2 (not indicated), CA1 (orange) and the subiculum (Sub; yellow)), three axes are indicated: the long or septotemporal axis (also referred to as the dorsoventral axis); the transverse or proximodistal axis, which runs parallel to the cell layer and starts at the DG; and the radial or superficial-to-deep axis, which is defined as being perpendicular to the transverse axis. In the parahippocampal region (green, blue, pink and purple shaded areas), a similar superficial-to-deep axis is used. Additionally, the presubiculum (PrS; medium blue) and parasubiculum (PaS; dark blue) are described by a septotemporal and proximodistal axis. The entorhinal cortex, which has a lateral (LEA; dark green) and a medial (MEA; light green) aspect, is described by a dorsolateral-to-ventromedial gradient and a rostrocaudal axis. The perirhinal cortex (consisting of Brodmann areas (A) 35 (pink) and 36 (purple)) and the postrhinal cortex (POR; blue-green) share the latter axis with the entorhinal cortex and are additionally defined by a dorsoventral orientation. The dashed lines in the left panel indicate the levels of two horizontal sections (a,b) and two coronal sections (c,d), which are shown in part B. All subfields of the parahippocampal–hippocampal region are colour-coded in correspondence with the interactive diagram in Supplementary information S1 (figure). A further description of the anatomical features of each subfield is provided in the legend of this supplementary information. C | A Nissl-stained horizontal cross section (enlarged from part Bb) in which the cortical layers and three-dimensional axes are marked. The Roman numerals indicate cortical layers. CA, cornu ammonis; dist, distal; dl, dorsolateral part of the entorhinal cortex; encl, enclosed blade of the DG; exp, exposed blade of the DG; gl, granule cell layer; luc, stratum lucidum; ml, molecular layer; or, stratum oriens; prox, proximal; pyr, pyramidal cell layer; rad, stratum radiatum; slm, stratum lacunosum-moleculare; vm, ventromedial part of the entorhinal cortex.

Retrosplenial cortex (RSC)

(article under construction)

The RSC is a neocortical structure situated in the midline of the cerebrum. It arches around the dorsocaudal half of the corpus callosum in the rat, where it is bordered rostrally by the anterior cingulate cortex, caudoventrally by the PHR and laterally by the parietal and visual cortices. The coordinate system that defines position within the RSC is explained in Figure XXX.

In the connectome, we follow the nomenclature as described by Vogt in 2004^[4], who subdivide the RSC into four areas referred to as A29a, A29b, A29c and A30. Most of the connectional papers do not separate A29a and b and the combined region will be referred to as A29ab in this paper (Figure XXX).

A29a is the most ventral subdivision and it differs from the dorsally adjacent A29b since it lacks a fully differentiated layered structure. Cytoarchitectonically, A29a has a homogenous layer II/III, while in A29b this layer is divided into a thin superficial densely packed zone and a less dense deeper zone ^[5]. A29a and A29b are distinguished from A29c most strikingly in layer III, which in A29ab has cells arranged in bands parallel to the pial surface, while in A29c layer III is thinner and the pyramidal cell bodies are randomly spaced ^[6]. An additional way to compare subregions is by looking at chemoarchitectonic features. A29ab shows parvalbumin stained cells in layers II, V and VI, which are not as apparent in A29c ^[7]. In AChE stained sections A29c layer IV shows a widening and increased strength of AChE staining compared to layer IV of A29b ^[8], ^[9], ^[10], ^[11]. Cytoarchitectonically, A30 shows an abrupt widening and a less dense packing of layer II/III compared to A29b and A29c ^[12], ^[13], ^[14], ^[15]. Also, A30 layer IV is wider than in A29b/A29c and A30 layer V neuronal cell bodies tend to be larger ^[16], ^[17]. In AChE stained sections, layer I-IV of A30 are evenly and darkly stained ^[18], whereas in A29c superficial and deep parts of layer I and layer IV are most densely stained ^[19].

Nomenclature

Where necessary, we converted the original nomenclature used in individual papers into the nomenclature of we follow. For this purpose, a “Rosetta table” was created, which allows easy conversion between different nomenclatures (Table 3a and 3b (3b under construction)).

Table 3a. HF-PHR Nomenclature.

Area	Subdivision	Subfield	Region synonym
Hippocampal Formation	Cornu Ammonis (CA)		Ammons Horn, hippocampus proper
		CA1	Regio superior, prosubiculum = transitional area CA1-Sub
		CA2
		CA3	Regio inferior
		CA4	Hilus of the Dentate Gyrus
	Dentate Gyrus (DG)
		Fascia dentata	Granular + molecular layer of DG
		Hilus fascia dentata	CA4
	Subiculum (Sub)
Parahippocampal Region	Presubiculum (PrS)		Brodmann Area 27, dorsal PrS = postsubiculum (Brodmann Area 48)
	Parasubiculum (PaS)		Brodmann Area 49
	Entorhinal Cortex (EC)		Brodmann Area 28
		Lateral Entorhinal Cortex (LEC)	Lateral Entorhinal Area (LEA), Brodmann Area 28a
		Medial Entorhinal Cortex (MEC)	Medial Entorhinal Area (MEA), Brodmann Area 28b
	Perirhinal Cortex (PER)
		Brodmann Area 35
		Brodmann Area 36	Ectorhinal Cortex
	Postrhinal Cortex (POR)

References

1. Amaral, D.G., Lavenex, P., 2007. Hippocampal Neuroanatomy. In: Andersen, P., Morris, R., Amaral, D.G., Bliss, T., O'Keefe, J. (Eds.), The Hippocampus Book, 1 ed. Oxford University Press, New York, pp. 37-114.
2. Burwell, R.D., Witter, M.P., 2002. Basic anatomy of the parahippocampal region in monkeys and rats. In: Witter, M.P., Wouterlood, F.G. (Eds.), The parahippocampal region: organization and role in cognitive function, 1 ed. Oxford University Press, New York, pp. 35-60.
3. Witter, M.P., Amaral, D.G., 2004. The hippocampal formation. In: Paxinos, G. (Ed.), The Rat Nervous System (Third edition). Elsevier Academic Press, San Diego, pp. 637-703.
4. Vogt, B.A., Vogt, L., and Farber, N.B. (2004). "Cingulate cortex and disease models," in The Rat Nervous System, ed. G. Paxinos. 3rd ed (San Diego, CA: Elsevier Academic Press), 705-727.
5. Vogt, B.A., and Peters, A. (1981). Form and distribution of neurons in rat cingulate cortex: areas 32, 24, and 29. J Comp Neurol 195, 603-625.
6. Van Groen, T., and Wyss, J.M. (1990). Connections of the retrosplenial granular a cortex in the rat. J Comp Neurol 300, 593-606.
7. Sripanidkulchai, K., and Wyss, J.M. (1987). The laminar organization of efferent neuronal cell bodies in the retrosplenial granular cortex. Brain Res 406, 255-269.
8. Jones, B.F., Groenewegen, H.J., and Witter, M.P. (2005). Intrinsic connections of the cingulate cortex in the rat suggest the existence of multiple functionally segregated networks. Neuroscience 133, 193-207.