Granule cells are the smallest cells found in the brain and are an extremely small type of neuron. Granule cells are found within the granular layer of the cerebellum (which is also known as layer II and IV layer), the inner most layer of cerebellar cortex with the middle layer being the Purkinje cell layer and the outermost being the Molecular layer), the dentate gyrus of the hippocampus, the superficial layer of the dorsal cochlear nucleus, and in the olfactory bulb.
Cerebellar granule cells account for nearly half of the neurons in the central nervous system. Granule 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.
Layer 4 granule cells of the cerebral cortex receive driving inputs from thalamus and convey driving inputs largely to supragranular layers 2-3, but also to infragranular layers of the cerebral cortex.
Granule cells in different brain regions are both functionally and anatomically diverse: the main 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 of granule cells are also the only major neuronal populations that undergo adult neurogenesis, while cerebellar and cortical granule cells do not. Granule cells have a structure typical of a neuron consisting of dendrites, a soma and an axon.
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. The axon has an extremely narrow diameter: ½ micron.
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.
Cerebellum granule cell 
The granule cells, produced by the rhombic lip, are found in the granule cell layer of the cerebellar cortex. They are small and numerous. They are characterized by a very small soma and several short dendrites which terminate with claw-shaped endings. In the transmission electron microscope, these cells are characterized by a darkly stained nucleus surrounded by a thin rim of cytoplasm. The axon ascends into the molecular layer where it splits to form parallel fibers.
Dentate granule cell 
The granule cell has a characteristic cone-shaped tree of spiny apical dendrites. The dendrite branches project throughout the entire molecular layer and the furthest tips of the dendritic tree end just at the hippocampal fissure or at the ventricular surface. The granule cells are tightly packed in the granular cell layer of the dentate gyrus.
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. Its axon projects to the molecular layer of the dorsal cochlear nucleus where it forms parallel fibers, also similar to cerebellar granule cells. The dorsal cochlear granule cells are small inhibitory interneurons which are developmentally related and thus resemble the cerebellar granule cell.
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. In the mammalian olfactory bulb, granule cells can process both synaptic input and output due to the presence of large spines.
Neuronal network 
Granule cells receive excitatory input from 3 or 4 mossy fibers originating from pontine nuclei. Mossy fibres make an excitatory connection onto granule cells which cause the granule cell to fire an action potential.
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 granule cells determines the cerebellar function as a whole.
Mossy fiber input 
The granule cells also give rise to 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 are exciting Purkinje cells but they are also causing the excitation of cells (GABA interneurons) which will inhibit Purkinje cells.
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 granule cell 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 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. 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.
Climbing fiber input 
Different patterns of mossy fibre input will produce unique patterns of activity in granule cells that can be modified by a teaching signal conveyed by the climbing fibre input. David Marr and James Albus suggested that the cerebellum operates as an adaptive filter, altering motor behaviour based on the nature of the sensory 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 fibre 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. The cerebellar granule cells also play a role in orchestrating the tonic conductances which control sleep in conjunction with the ambient levels of GABA which are found in the brain.
- 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. Young and old dentate granule cells have distinct roles in memory function. Adult-born granule cells function in pattern separation whereas old granule cells contribute to rapid pattern completion.
- Dorsal cochlear granule cells
Pyramidal cells from the primary auditory cortex project directly on to the cochlear nucleus. This is important in the acoustic startle reflex, in which the pyramidal cells modulate the secondary orientation reflex and the granule cell input is responsible for appropriate orientation. This is because the signals received by the granule cells contain information about the head position. Granule cells in the dorsal cochlear nucleus play a role in the perception and response to sounds in our environment.
- 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. 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. The olfactory bulb transmits smell information from the nose to the brain, and is thus necessary for a proper sense of smell.
Critical factors for function 
Calcium dynamics are essential for several functions of granule cells such as changing membrane potential, synaptic plasticity, apoptosis, and regulation of gene transcription. The nature of the calcium signals that control the presynaptic and postsynaptic function of the olfactory bulb granule cells spines is mostly unknown.
- 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  and is essential for protecting the granule cells from damage. NO is also responsible for neuroplasticity and motor learning.
Role in Disease 
- Altered morphology of dentate granule cells
TrkB is responsible for the maintenance of normal synaptic connectivity of the dentate granule cells. TrkB also regulates the specific morphology (biology) of the granule cells and is thus said to be important in regulating neuronal development, neuronal plasticity, learning, and the development of epilepsy. The TrkB regulation of granule cells is important in preventing memory deficits and limbic epilepsy. This is due to the fact that dentate granule cells play a critical role in the function of the entorhinal-hippocampal circuitry in health and disease. Dentate granule cells are situated to regulate the flow of information into the hippocampus, a structure required for normal learning and memory.
- Decreased granule cell neurogenesis
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 granule cells may result in aberrant connections that result in the hippocampal network plasticity associated with epileptogenesis.
- Shorter granule cell dendrites
Patients suffering from Alzheimer's have shorter granule cell dendrites. Furthermore, the dendrites were less branched and had fewer spines than those in patients not suffering with Alzheimer's. However, granule cell dendrites are not an essential component of senile plaques and these plaques have no direct effect on granule cells 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.
- Position of granule cells within layers of the cerebella cortex
- Architecture of the Cerebellum
- The Cerebellum
- C. Reyher, J Liibke, W Larsen, G Hendrix, M Shipley, and H Baumgarten (1991). "Olfactory Bulb Granule Cell Aggregates: Morphological Evidence for lnterperikaryal Electrotonic Coupling via Gap Junctions". The Journal of Neuroscience. 11(6): 1465–495.
- Llinas, Walton and Lang (2004). The Synaptic Organization of the Brain. Oxford University Press. doi:10.1093/acprof:oso/9780195159561.003.0007.
- Claiborne BJ, Amaral DG, Cowan WM (1990). "A quantitative three-dimensional analysis of granule cell dendrites in the rat dentate gyrus". The Journal of Comparative Neurology 302: 206–219. doi:10.1002/cne.903020203.
- David G. Amaral, Helen E. Scharfman, and Pierre Lavenex (2007). Progress in Brain Research - dentate gyrus: fundamental neuroanatomical organization 163. pp. 3–22. doi:10.1016/S0079-6123(07)63001-5.
- Mugnaini E, Osen KK, Dahl AL, Friedrich VL Jr, Korte G. (1980). "Fine structure of granule cells and related interneurons (termed Golgi cells) in the cochlear nuclear complex of cat, rat and mouse". Journal of Neurocytology 9(4): 537–70. doi:10.1007/BF01204841.
- E. Young, O. Oertel (2004). The Synaptic Organization of the Brain. Oxford University Press. doi:10.1093/acprof:oso/9780195159561.003.0004.
- K. Neville,L. Haberly (2004). The Synaptic Organization of the Brain. Oxford University Press. doi:10.1093/acprof:oso/9780195159561.003.0010.
- V Egger, K Svoboda, and Z Mainen (2005). "Dendrodendritic Synaptic Signals in Olfactory Bulb Granule Cells: Local Spine Boost and Global Low-Threshold Spike". The Journal of Neuroscience. 25(14): 3521–3530. doi:10.1523/JNEUROSCI.4746-04.2005.
- Huang CM, Wang L, Huang RH (2006). "Cerebellar granule cell: ascending axon and parallel fiber". European Journal of Neuroscience. 23(7): 1731–1737. doi:10.1111/j.1460-9568.2006.04690.x.
- M Manto and C De Zeeuw (2012). "Diversity and Complexity of Roles of Granule Cells in the Cerebellar Cortex". The Cerebellum. doi:10.1007/s12311-012-0365-7.
- M. Bear and M. Paradiso (2006). Neuroscience: Exploring the Brain. Lippincott Williams & Wilkins. p. 855. ISBN 9780781760034.
- M Schonewille, G Spitzmaul, A Badura , I Klein, Y Rudhard, W Wisden, C Hübner, C De Zeeuw and T Jentsch (2012). "Raising cytosolic Cl(-) in cerebellar granule cells affects their excitability and vestibulo-ocular learning.". The EMBO journal. doi:10.1038/emboj.2011.488.
- Eccles JC, Ito M, Szentagothai J (1967). The cerebellum as a neural machine. Springer-Verlag. p. 56.
- F Bengtssona and H Jörntell (2009). "Sensory transmission in cerebellar granule cells relies on similarly coded mossy fiber inputs.". PNAS. 106(7): 2389–2394. doi:10.1073/pnas.0808428106.
- A Arenz, E Bracey and T Margrie (2009). "Sensory representations in cerebellar granule cells.". Current Opinion in Neurobiology. 19(4): 445–451. doi:10.1016/j.conb.2009.07.003.
- Marr D (1969). "A theory of cerebellar cortex". The Journal of Physiology 202: 437–70.
- M Colicos, P Dash (1996). "Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits". Brain Research. 739(1-2): 120–131. doi:10.1016/S0006-8993(96)00824-4.
- T Nakashiba, J Cushman, K Pelkey, S Renaudineau, D Buhl, T McHugh, V Rodriguez Barrera, R Chittajallu, K Iwamoto, C McBain, M Fanselow and S Tonegawa (2012). "Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion". Cell. doi:10.1016/j.cell.2012.01.046.
- Weedman DL, Ryugo DK (1996). "Projections from auditory cortex to the cochlear nucleus in rats: synapses on granule cell dendrites". The Journal of Comparative Neurology. 371(2): 311–324. doi:10.1002/(SICI)1096-9861(19960722)371:2<311::AID-CNE10>3.0.CO;2-V.
- R Balu, R Pressler, and B Strowbridge (2007). "Multiple Modes of Synaptic Excitation of Olfactory Bulb Granule Cells". The Journal of Neuroscience. 27(21): 5621–5632. doi:10.1523/JNEUROSCI.4630-06.2007.
- R Feil , J Hartmann, C Luo, W Wolfsgruber, K Schilling, S Feil etal (2003). "Impairment of LTD and cerebellar learning by Purkinje cell specific ablation of cGMP-dependent protein kinase I.". The Journal of Cell Biology. 163(2): 295–302. doi:10.1083/jcb.200306148.
- S Danzer, R Kotloski, C Walter, Maya Hughes and J McNamara (2008). "Altered morphology of hippocampal dentate granule cell presynaptic and postsynaptic terminals following conditional deletion of TrkB". Hippocampus. 18(7): 668–678. doi:10.1002/hipo.20426.
- S Danzer (2012). "Depression, stress, epilepsy and adult neurogenesis". Experimental Neurology. 233(1): 22–32. doi:10.1016/j.expneurol.2011.05.023.
- J. Parent, T Yu, R Leibowitz, D Geschwind, R Sloviter, and D Lowenstein (1997). "Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus". The Journal of Neuroscience. 17(10): 3727–3738.
- Einstein G, Buranosky R, Crain BJ (1994). "Dendritic pathology of granule cells in Alzheimer's disease is unrelated to neuritic plaques". The Journal of Neuroscience. 14(8): 5077–5088.
- Wakabayashi K, Hansen LA, Vincent I, Mallory M, Masliah E (1997). "Neurofibrillary tangles in the dentate granule cells of patients with Alzheimer's disease, Lewy body disease and progressive supranuclear palsy". Acta Neuropathologica. 93(1): 7–12. doi:10.1007/s004010050576.