The dentate gyrus is an integral region of the hippocampal formation. It is responsible for the formation of our episodic memory as well as the exploration of new environments. It is, therefore, part of the system that gives us autobiographical and episodic memories. This article will discuss the anatomy, individual cells, molecular layers, functions, and clinical relevance of the dentate gyrus.
The dentate gyrus is a part of the hippocampal formation, a group of structures that lie in the medial temporal lobe (also part of this formation is the hippocampus proper and the subiculum).
The dentate gyrus has three distinct layers (molecular layer, granule cell layer and polymorphic layer). The molecular layer is relatively cell free and is occupied by the dendrites of the dentate granule cells. The granular layer is the principal layer, and comprises mainly granule cells closely packed together. The dentate pyramidal basket cell is often found on the border between the granular and the polymorphic layer. The polymorphic layer itself lies within the granule cell layer. The most abundant cells found here are the mossy cells.
The ‘CA3 field’ of the hippocampus is the ultimate destination of the neurons that arise from the dentate gyrus. The hippocampal formation is a relatively unique region of the brain, in that many of its neurons are unidirectional.
The dentate granule cell
The branches of the granule cells extend through the molecular layer, and the furthest tips of the dendritic tree terminate just proximal to the hippocampal fissure. Virtually all of the excitatory input to the granule cells can be found on the dendritic spines. These cells tend to be tightly packed together, with no glial cells in between. The density of the cells varies according to their respective position. Septal granule cells are more densely packed than temporal cells. There is also significant evidence that they use glutamate as their primary neurotransmitter.
The dentate pyramidal basket cell
The brain is full of both excitatory and inhibitory neurons. Granule cells (that use glutamate) are excitatory, whereas the dentate pyramidal basket cell is the primary inhibitory interneuron found in the dentate gyrus. They are most commonly located in the border between the polymorphic and granule cell layer. The name also clearly implies that they have pyramidal shaped bodies. They have singular dendrites that reach into the molecular layer, and will further branch into smaller branches.
The quantity of basket cells also varies according to whether you are in the septotemporal or transverse regions of the dentate gyrus. The basket to granule cells ratio is slightly higher suprapyramidally, in both the septal and temporal regions. These basket cells synapse primarily on the cell bodies and dendritic shafts of the apical dendrites of the granule cells.
These granule cells also give rise to unmyelinated axons, called ‘mossy fibres’ by Ramón y Cajal. They have large cell bodies that are triangular in shape. These mossy fibres have uniquely large boutons (presynaptic terminals), which enable synaptic connections to be made with both the CA3 cells of the hippocampus, and the mossy cells of the polymorphic layer.
Each of these mossy fibres gives rise to around 7 thin collaterals that go on to synapse in the CA3 field of the hippocampus. They also synapse in the polymorphic layer, where the vast majority will terminate on GABAergic inhibitory interneurons. Each of these collaterals will further subdivide; each one will have numerous synaptic spherical varicosities distributed evenly along its course. These collaterals may occasionally enter the granule layer (the majority of these terminate on pyramidal basket cells), but never enter the molecular layer.
Neurons of the molecular layer
The molecular layer of the dentate gyrusprimarily contains:
- the dendrites of granule cells
- the polymorphic layer cells
- the pyramidal basket cells
- the axons of the terminal entorhinal cortex neurons and from a few other regions (presubiculum, parasubiculum).
There are primarily two nerve cell types within the molecular layer. These are the MOPP cell (molecular layer perforant path-associated cell) which are located deep in the molecular layer, with a multipolar/triangular body, and terminate in the outer two thirds of the molecular layer.
The second is a ‘chandelier’ like cell found in the neocortex, and found immediately adjacent to the superficial portion of the granule cell layer. It is also sometimes referred to as an axo-axonic cell, as it descends from the molecular layer to the granule cell layer. Here they have numerous collaterals, and terminate exclusively in the initial axon segments of the granule cells. Each of these ‘chandelier’ cells may innervate as many as 1000 granule cells. These cells release GABA and have an inhibitory effect on granule cells. The internal third of the molecular layer receives projections from the polymorphic layer exclusively.
Neurons of the polymorphic cell layer
As well as mossy cells, there are also fusiform cells in the polymorphic layer. These cells have further sub types, but they all descend into the outer two thirds of the molecular layer, and deliver GABA/somatostatin.
Entorhinal cortex projection
The entorhinal cortex is the primary source of input for the dentate gyrus (mainly the cells within layer 2, but also layers 5 and 6 through the perforant pathway). The vast majority of the entorhinal nerve cells will terminate within the outer two thirds of the molecular layer. These synapses are formed with the dendritic spines of the granule cells.
There are no neurons that run in the reverse direction (dentate gyrus to entorhinal cortex). The entorhinal cortex provides the hippocampal formation with a large quantity of its sensory input, and because this sensory information ultimately terminates in the dentate gyrus, we can regard it as the first step in the formation of ‘episodic memories’.
Presubiculum and parasubiculum
There is also evidence that the dentate gyrus receives some input from the presubiculum and parasubiculum. There is very little knowledge about what or where these nerve cells would synapse, or what neurotransmitter they use. The presubiculum is a region that receives all its input from the thalamus, and hence provides a link from the thalamus to the dentate gyrus.
The locus coeruleus is a noradrenergic nucleus in the brainstem that supplies the dentate gyrus. They primarily terminate in the polymorphic layer. There is also some dopaminergic input from the ventral tegmental area (which also mainly terminate in the polymorphic layer). The raphe nuclei supply serotonergic input to the polymorphic layer mainly, and focus on GABAergic interneurons.
The dentate gyrus receives the vast majority of its input from the entorhinal cortex and some input from the subcortical structures. The majority of the input from subcortical structures arises from the septal nuclei (the diagonal band of Broca and the medial septal nucleus). These nuclei project heavily to the polymorphic layer.
A large percentage of the septal nuclei fibres that project to the dentate gyrus are cholinergic. There are however other septal nerve cells that are GABAergic i.e. inhibitory. The excitatory and inhibitory septal cells target different cell types preferentially: GABAergic fibres to GABAergic non-pyramidal cells mainly in the polymorphic layer, and cholinergic fibres to the inner third of the molecular layer of the dentate gyrus, as well as mossy fibres.
There is a population of large cells in the supramammillary area. This supplies excitatory (glutaminergic) input (some cells also release substance P and calretinin) to the proximal dendrites of the granule cells mainly.