The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies)

Abstract

The dentate gyrus is a simple cortical region that is an integral portion of the larger functional brain system called the hippocampal formation. In this review, the fundamental neuroanatomical organization of the dentate gyrus is described, including principal cell types and their connectivity, and a summary of the major extrinsic inputs of the dentate gyrus is provided. Together, this information provides essential information that can serve as an introduction to the dentate gyrus--a "dentate gyrus for dummies."

Fig. 1

The rat hippocampal formation. (A) Nissl-stained horizontal section through the hippocampal formation of the rat. The major fields are indicated. Projections (1) originate from layer II of the entorhinal cortex (EC) and terminate in the molecular layer of the dentate gyrus (DG) and in the stratum lacunosum-moleculare of the CA3 field of the hippocampus. An additional component of the perforant path originates in layer III and terminates in the CA1 field of the hippocampus and the subiculum. Granule cells of the DG give rise to the mossy fibers (2) that terminate both within the polymorphic layer of the DG and within stratum lucidum of the CA3 field of the hippocampus. The CA3 field, in turn, gives rise to the Schaffer collaterals (3) that innervate the CA1 field of the hippocampus. Pyramidal cells in CA1 project to the subiculum and to the deep layers of the EC. The subiculum also gives rise to projections to the deep layers of the EC. (B) Line drawing to illustrate the major regional and laminar organization of the DG. The DG is divided into a molecular layer (ml) a granule cell layer (gcl) and a polymorphic layer (pl). The molecular layer is divided into three sublayers based on the laminar organization of inputs. The hippocampus is divided into CA3, CA2 and CA1 subfields. Within CA3, a number of layers are defined. The main cell layer is the pyramidal cell layer (pcl). Deep to the pyramidal cell layer is the stratum oriens (so); deep to this is the white matter of the alveus (al). Superficial to the pyramidal cell layer is stratum lucidum (sl), stratum radiatum (sr) and stratum lacunosum-moleculare (sl-m). Fields CA2 and CA1 have the same layers as CA3 except for stratum lucidum. The remainder of the hippocampal formation is made up of the subiculum (Sub), presubiculum (Pre), parasubiculum (Para) and EC. Layers of these latter structures are indicated with roman numerals. Additional abbreviations: ab, angular bundle; fi, fimbria; hf, hippocampal fissure. (C) Schematic illustration of DG and hippocampus to illustrate position of suprapyramidal blade, infrapyramidal blade and crest of the DG. This model is used in subsequent illustrations to demonstrate the major cell types and connections of the DG. (See Color Plate 1.1 in color plate section.)

Fig. 2

Comparative Nissl and Timm's staining of the rat and monkey dentate gyrus. Approximately the same portions of the rat (A & B) and monkey (C & D) hippocampal formation are illustrated. The magnification of the paired images are different. The increased complexity of the hilar region in the monkey compared to the rat is obvious in these photomicrographs. In the monkey, the CA3 field inserts more deeply into the dentate gyrus and accounts for a much greater area of the hilar region. While the darkly stained polymorphic layer is pronounced in the rat, it is much thinner in the monkey brain. The condensed layer of mossy fibers is also much more pronounced in the rat compared to the monkey. Also note that the strict lamination of the molecular layer into thirds in the rat is not as sharp as in the monkey. This corresponds to a more gradient-like termination of the medial and lateral perforant paths in the monkey compared to the rat. Calibration, 250 μm (A, B); 350 μm (C, D).

Fig. 3

Horizontal sections through the rat hippocampal formation. This figure illustrates a more dorsally situated (A) and a more ventrally situated (B) horizontal section through the rat hippocampal formation. The approximate level of the section is illustrated on a 3D reconstruction of a magnetic resonance image series of the rat brain. Subtle differences in the cytoarchitectonic organization are seen throughout the hippocampal formation. The dentate gyrus, takes on a more “V” shape dorsally and a more “U” shape ventrally. Calibration bar = 250 μm. (See Color Plate 1.3 in color plate section.)

Fig. 4

The dentate granule cell. The characteristic features of the dentate granule cell are illustrated, including its axonal arbor. A collateral plexus gives rise to numerous (∼200) typical synapses on cells located within the polymorphic layer. Most of these synapses are onto the dendrites of inhibitory interneurons. Some of the large mossy fiber expansions are also distributed in the polymorphic layer. Many of these terminate on the proximal dendrites of mossy cells. The mossy fiber axons ultimately enter the CA3 field where they travel through the full transverse extent of the field. On their course, they terminate with mossy fiber expansions on a small number (15–20) of CA3 pyramidal cells. Additional abbreviations: gc, granule cell; pc, pyramidal cell. (See Color Plate 1.4 in color plate section.)

Fig. 5

The dentate granule cell. A photomicrograph (A) and line drawing (B) of a prototypical granule cell that was filled with Lucifer yellow in a hippocampal slice. The dendrites arise primarily from the apical surface of the cell body, and the axon emerges from the basal surface. The spiny dendrites extend into the molecular layer until the hippocampal fissure, and the axon collateralizes profusely within the polymorphic layer. Calibration bar = 25 μm (A), 20 μm (B).

Fig. 6

The pyramidal basket cell. The cell body of the pyramidal basket cell is located at the interface between the granule cell layer and the polymorphic cell layer. The axon (arrow) emerges from the apical dendrite. Collaterals of this axon form a curtain of terminals that synapse with the granule cell bodies. Additional abbreviations: pbc, pyramidal basket cell. (See Color Plate 1.6 in color plate section.)

Fig. 7

The pyramidal basket cell. A prototypical pyramidal basket cell is shown after intracellular injection of Neurobiotin. The montage that was created after visualization of the cell (A) and line drawing (B) illustrate the characteristics of this cell type. An arrow points to the axon. Calibration bar = 25 μm (A), 40 μm (B).

Fig. 8

The mossy cell. A line drawing of a mossy cell (mc) in the polymorphic layer. The axon (arrow) develops a plexus within the polymorphic layer, and also an ipsilateral projection to the inner molecular layer, known as the associational pathway. The main axon also projects contralaterally to the inner molecular layer, forming the commissural pathway. The ipsilateral projection increases in density with distance from the cell body of origin. (See Color Plate 1.8 in color plate section.)

Fig. 9

The mossy cell. A montage of several focal planes (A), and line drawing (B) of a classic mossy cell, illustrating the characteristic thorny excrescences and dendritic tree of this cell type. Thorny excrescences are present proximal to the soma. The dendrites of the cell extend throughout nearly the entire polymorphic region, but few enter either the granule cell or molecular layers. Calibration bar = 25 μm (A), 50 μm (B).

Fig. 10

The long-spined cell. A montage (A) and line drawing (B) of a long-spined cell in the polymorphic layer. The extremely long spines that characterize this cell type are marked by arrowheads, and can be proximal as well as distal to the cell body, although in this example they were primarily located along distal dendrites. The axon of this cell collateralized in the molecular layer. Some of the long-spined cells correspond to the GABAergic interneurons that colocalize somatostatin, so-called HIPP cells. Calibration bar = 25 μm (A), 50 μm (B).

Fig. 11

Neurons of the polymorphic region. The summary figure reprinted from Amaral (1978) illustrates the diversity of cells types within the dentate gyrus and proximal CA3 region of the rat. Based on Golgi staining and cameral lucida drawings of individual neurons from multiple preparations. See original paper for description of cell types.

Plate 1.1

The rat hippocampal formation. (A) Nissl-stained horizontal section through the hippocampal formation of the rat. The major fields are indicated. Projections (1) originate from layer II of the entorhinal cortex (EC) and terminate in the molecular layer of the dentate gyrus (DG) and in the stratum lacunosum-moleculare of the CA3 field of the hippocampus. An additional component of the perforant path originates in layer III and terminates in the CA1 field of the hippocampus and the subiculum. Granule cells of the DG give rise to the mossy fibers (2) that terminate both within the polymorphic layer of the DG and within stratum lucidum of the CA3 field of the hippocampus. The CA3 field, in turn, gives rise to the Schaffer collaterals (3) that innervate the CA1 field of the hippocampus. Pyramidal cells in CA1 project to the subiculum and to the deep layers of the EC. The subiculum also gives rise to projections to the deep layers of the EC. (B) Line drawing to illustrate the major regional and laminar organization of the DG. The DG is divided into a molecular layer (ml) a granule cell layer (gcl) and a polymorphic layer (pl). The molecular layer is divided into three sublayers based on the laminar organization of inputs. The hippocampus is divided into CA3, CA2 and CA1 subfields. Within CA3, a number of layers are defined. The main cell layer is the pyramidal cell layer (pcl). Deep to the pyramidal cell layer is the stratum oriens (so); deep to this is the white matter of the alveus (al). Superficial to the pyramidal cell layer is stratum lucidum (sl), stratum radiatum (sr) and stratum lacunosum-moleculare (sl-m). Fields CA2 and CA1 have the same layers as CA3 except for stratum lucidum. The remainder of the hippocampal formation is made up of the subiculum (Sub), presubiculum (Pre), parasubiculum (Para) and EC. Layers of these latter structures are indicated with roman numerals. Additional abbreviations: ab, angular bundle; fi, fimbria; hf, hippocampal fissure. (C) Schematic illustration of DG and hippocampus to illustrate position of suprapyramidal blade, infrapyramidal blade and crest of the DG. This model is used in subsequent illustrations to demonstrate the major cell types and connections of the DG. (For B/W version, see page 4 in the volume.)

Plate 1.3

Horizontal sections through the rat hippocampal formation. This figure illustrates a more dorsally situated (A) and a more ventrally situated (B) horizontal section through the rat hippocampal formation. The approximate level of the section is illustrated on a 3D reconstruction of a magnetic resonance image series of the rat brain. Subtle differences in the cytoarchitectonic organization are seen throughout the hippocampal formation. The dentate gyrus, takes on a more “V” shape dorsally and a more “U” shape ventrally. Calibration bar = 250 μm. (For B/W version, see page 7 in the volume.)

Plate 1.4

The dentate granule cell. The characteristic features of the dentate granule cell are illustrated, including its axonal arbor. A collateral plexus gives rise to numerous (∼200) typical synapses on cells located within the polymorphic layer. Most of these synapses are onto the dendrites of inhibitory interneurons. Some of the large mossy fiber expansions are also distributed in the polymorphic layer. Many of these terminate on the proximal dendrites of mossy cells. The mossy fiber axons ultimately enter the CA3 field where they travel through the full transverse extent of the field. On their course, they terminate with mossy fiber expansions on a small number (15–20) of CA3 pyramidal cells. Additional abbreviations: gc, granule cell; pc, pyramidal cell. (For B/W version, see page 8 in the volume.)

Plate 1.6

The pyramidal basket cell. The cell body of the pyramidal basket cell is located at the interface between the granule cell layer and the polymorphic cell layer. The axon (arrow) emerges from the apical dendrite. Collaterals of this axon form a curtain of terminals that synapse with the granule cell bodies. Additional abbreviations: pbc, pyramidal basket cell. (For B/W version, see page 12 in the volume.)

Plate 1.8

The mossy cell. A line drawing of a mossy cell (mc) in the polymorphic layer. The axon (arrow) develops a plexus within the polymorphic layer, and also an ipsilateral projection to the inner molecular layer, known as the associational pathway. The main axon also projects contralaterally to the inner molecular layer, forming the commissural pathway. The ipsilateral projection increases in density with distance from the cell body of origin. (For B/W version, see page 13 in the volume.)