Granule cell
The name granule cell has been used for a number of different types of neurons whose only common feature is that they all have very small cell bodies. Granule cells 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.
Layer 4 granule cells of the cerebral cortex receive inputs from the thalamus and send projections to supragranular layers 2–3, but also to infragranular layers of the cerebral cortex.
Structure
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
Dendrites: Each granule cell 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.[citation needed] The axon has an extremely narrow diameter: ½ micrometre.
Synapse: 100–300,000 granule cell axons synapse onto a single Purkinje cell.[citation needed]
The existence of
Cerebellar granule cell
The granule cells, produced by the
Dentate gyrus granule cell
The principal cell type of the dentate gyrus is the granule cell. The dentate gyrus granule cell has an elliptical cell body with a width of approximately 10 μm and a height of 18μm.[3]
The granule cell has a characteristic cone-shaped tree of spiny apical
Dorsal cochlear nucleus granule cell
The granule cells in the dorsal cochlear nucleus are small neurons with two or three short dendrites that give rise to a few branches with expansions at the terminals. The dendrites are short with claw-like endings that form glomeruli to receive mossy fibers, similar to cerebellar granule cells.[5] Its axon projects to the molecular layer of the dorsal cochlear nucleus where it forms parallel fibers, also similar to cerebellar granule cells.[6] The dorsal cochlear granule cells are small excitatory
Olfactory bulb granule cell
The main intrinsic granule cell in the vertebrate olfactory bulb lacks an axon (as does the accessory neuron). Each cell gives rise to short central dendrites and a single long apical dendrite that expands into the granule cell layer and enters the mitral cell body layer. The dendrite branches terminate within the outer plexiform layer among the dendrites in the olfactory tract.[7] In the mammalian olfactory bulb, granule cells can process both synaptic input and output due to the presence of large spines.[8]
Function
Neural pathways and circuits of the cerebellum
Cerebellar granule cells receive excitatory input from 3 or 4 mossy fibers originating from pontine nuclei. Mossy fibers make an excitatory connection onto granule cells which cause the granule cell to fire an action potential.
The axon of a cerebellar granule cell splits to form a
The parallel fibers are sent up through the
This connection is excitatory as
The parallel fibers and ascending axon synapses from the same granule cell fire in synchrony which results in excitatory signals. In the cerebellar cortex there are a variety of inhibitory neurons (
Plasticity of the synapse between a parallel fiber and a Purkinje cell is believed to be important for motor learning.[11] The function of cerebellar circuits is entirely dependent on processes carried out by the granular layer. Therefore, the function of granule cells determines the cerebellar function as a whole.[12]
Mossy fiber input on cerebellar granule cells
Granule cell dendrites also synapse with distinctive unmyelinated axons which Santiago Ramón y Cajal called mossy fibers[4] Mossy fibers and golgi cells both make synaptic connections with granule cells. Together these cells form the glomeruli.[10]
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
Mossy fiber input codes are conserved during
Each granule cell is receiving an input from two different mossy fiber 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 granule cells 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.[15] The signal a granule cell receives from a Mossy fiber depends on the function of the mossy fiber itself. Therefore, granule cells are able to integrate information from the different mossy fibers and generate new patterns of activity.[15]
Climbing fiber input on cerebellar granule cells
Different patterns of mossy fiber input will produce unique patterns of activity in granule cells that can be modified by a teaching signal conveyed by the climbing fiber input.
Since multiple (~200,000) granule cells synapse onto a single Purkinje cell, the effects of each parallel fiber can be altered in response to a “teacher signal” from the climbing fiber input.
Specific functions of different granule cells
- Cerebellum granule cells
David Marr suggested that the granule cells encode combinations of mossy fiber inputs. In order for the granule cell to respond, it needs to receive active inputs from multiple mossy fibers. The combination of multiple inputs results in the cerebellum being able to make more precise distinctions between input patterns than a single mossy fiber would allow.[16] The cerebellar granule cells also play a role in orchestrating the tonic conductances which control sleep in conjunction with the ambient levels of
- Dentate granule cells
Loss of dentate gyrus neurons from the hippocampus results in spatial memory deficits. Therefore, dentate granule cells are thought to function in the formation of spatial memories [17] and of episodic memories.[18] Immature and mature dentate granule cells have distinct roles in memory function. Adult-born granule cells are thought to be involved in pattern separation whereas old granule cells contribute to rapid pattern completion.[19]
- Dorsal cochlear granule cells
Pyramidal cells from the
- Olfactory bulb granule cells
Inhibition generated by granule cells, the most common GABAergic cell type in the olfactory bulb, plays a critical role in shaping the output of the olfactory bulb.[21] There are two types of excitatory inputs received by GABAergic granule cells; those activated by an AMPA receptor and those activated by a NMDA receptor. This allows the granule cells to regulate the processing of the sensory input in the olfactory bulb.[21] The olfactory bulb transmits smell information from the nose to the brain, and is thus necessary for a proper sense of smell. Granule cells in the olfactory bulb have also been found to be important in forming memories linked with scents.[22]
Critical factors for function
- Calcium
Calcium dynamics are essential for several functions of granule cells such as changing
- Nitric oxide
Granule neurons have high levels of the neuronal isoform of nitric oxide synthase. This enzyme is dependent on the presence of calcium and is responsible for the production of nitric oxide (NO). This neurotransmitter is a negative regulator of granule cell precursor proliferation which promotes the differentiation of different granule cells. NO regulates interactions between granule cells and glia[10] and is essential for protecting the granule cells from damage. NO is also responsible for neuroplasticity and motor learning.[23]
Role in disease
Altered morphology of dentate granule cells
Decreased granule cell neurogenesis
Both epilepsy and depression show a disrupted production of adult-born hippocampal granule cells.[25] Epilepsy is associated with increased production - but aberrant integration - of new cells early in the disease and decreased production late in the disease.[25] 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
Shorter granule cell dendrites
Patients with
See also
List of distinct cell types in the adult human body
References
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