The term granule cell (GC) is used by anatomists for a number of different types of neurons whose only common feature is that they all have very small cell bodies. They are found within the granular layer of the cerebellum, the dentate gyrus of the hippocampus, the superficial layer of the dorsal cochlear nucleus, the olfactory bulb, and the cerebral cortex.
Cerebellar granule cells account for the majority of neurons in the human brain. These cells receive excitatory input from mossy fibers originating from pontine nuclei.
Cerebellar granule cells send parallel fibers up through the Purkinje layer into the molecular layer where they branch out and spread through Purkinje cell dendritic arbors. These parallel fibers form thousands of excitatory granule-cell-Purkinje-cell synapses onto the intermediate and distal dendrites of Purkinje cells using glutamate as a neurotransmitter.
Structure Of Granule Cells
Granule cells in different brain regions are both functionally and anatomically diverse: the only thing they have in common is smallness. For instance, olfactory bulb granule cells are GABAergic and axonless, while granule cells in the dentate gyrus have glutamatergic projection axons.
These two populations are also the only major neuronal populations that undergo adult neurogenesis, while cerebellar and cortical GCs do not. Granule cells (save for those of the olfactory bulb) have a structure typical of a neuron consisting of dendrites, a soma (cell body) and an axon.
Dendrites: Each GC has 3 – 4 stubby dendrites which end in a claw. Each of the dendrites are only about 15 μm in length.
Soma: Granule cells all have a small soma diameter of approximately 10 μm.
Axon: Each granule cell sends a single axon onto the Purkinje cell dendritic tree. The axon has an extremely narrow diameter: ½ micron.
Synapse: 100-300,000 GC axons synapse onto a single Purkinje cell.
The existence of gap junctions between granule cells allows multiple neurons to be coupled to one another allowing multiple cells to act in synchronization and to allow signalling functions necessary for granule cell development to occur.
Neuronal Network Of The Cerebellar Cortex
Cerebellar granule cells receive excitatory input from 3 or 4 mossy fibers originating from pontine nuclei. Mossy fibres make an excitatory connection which cause the granule cell to fire an action potential.
The axon of a cerebellar granule cell splits to form a parallel fiber which innervates Purkinje cells. The vast majority of GC axonal synapses are found on the parallel fibers.
The parallel fibers are sent up through the Purkinje layer into the molecular layer where they branch out and spread through Purkinje cell dendritic arbors. These parallel fibers form thousands of excitatory Granule-cell-Purkinje-cell synapses onto the dendrites of Purkinje cells.
This connection is excitatory as glutamate is released.
The parallel fibers and ascending axon synapses from the same granule cell fire in synchronisation which results in excitatory signals. In the cerebellar cortex there are a variety of inhibitory neurons (interneurons). The only excitatory neurons present in the cerebellar cortex are granule cells.
Plasticity of the synapse between a parallel fiber and a Purkinje cell is believed to be important for motor learning. The function of cerebellar circuits is entirely dependent on processes carried out by the granular layer. Therefore, the function of GCs determines the cerebellar function as a whole.
Mossy Fiber Input On Cerebellar Granule Cells
Granule cell dendrites also synapse with distinctive unmyelinated axons which Santiago Ramón y Cajal called mossy fibers Mossy fibers and golgi cells both make synaptic connections with granule cells. Together these cells form the glomeruli.
Granule cells are subject to feed-forward inhibition: granule cells excite Purkinje cells but also excite GABAergic interneurons that inhibit Purkinje cells.
Granule cells are also subject to feedback inhibition: Golgi cells receive excitatory stimuli from granule cells and in turn send back inhibitory signals to the granule cell.
Mossy fiber input codes are conserved during synaptic transmission between granule cells, suggesting that innervation is specific to the input that is received. Granule cells do not just relay signals from mossy fibers, rather they perform various, intricate transformations which are required in the spatiotemporal domain.
Each GC is receiving an input from two different mossy fibre inputs. The input is thus coming from two different places as opposed to the granule cell receiving multiple inputs from the same source.
The differences in mossy fibers that are sending signals to the granule cells directly effects the type of information that GCs translate to Purkinje cells. The reliability of this translation will depend on the reliability of synaptic activity in granule cells and on the nature of the stimulus being received. The signal a granule cell receives from a Mossy fiber depends on the function of the mossy fiber itself.
Therefore, GCs are able to integrate information from the different mossy fibers and generate new patterns of activity.
Both epilepsy and depression show a disrupted production of adult-born hippocampal granule cells. Epilepsy is associated with increased production – but aberrant integration – of new cells early in the disease and decreased production late in the disease.
Aberrant integration of adult-generated cells during the development of epilepsy may impair the ability of the dentate gyrus to prevent excess excitatory activity from reaching hippocampal pyramidal cells, thereby promoting seizures. Long-lasting epileptic seizure stimulate dentate granule cell neurogenesis. These newly born dentate GCs may result in aberrant connections that result in the hippocampal network plasticity associated with epileptogenesis.
However, granule cell dendrites are not an essential component of senile plaques and these plaques have no direct effect on GCs in the dentate gyrus. The specific neurofibrillary changes of dentate granule cells occur in patients suffering from Alzheimer’s, Lewy body variant and progressive supranuclear palsy.
Llinas, Walton and Lang (2004)
The Synaptic Organization of the Brain
Oxford University Press ISBN-13: 978-0195159561
Image: Haphip CC BY-SA 3.0