Editing Cerebellum (section)

==== Layers of the cerebellar cortex ====
===== Molecular layer =====
The top, outermost layer of the cerebellar cortex is the molecular layer. This layer contains the flattened [[dendrite|dendritic trees]] of Purkinje cells, and the huge array of parallel fibers, from the granular layer, that penetrate the Purkinje cell dendritic trees at right angles. The molecular layer also contains two types of inhibitory interneuron: [[stellate cell]]s and [[basket cell]]s. Both stellate and basket cells form [[gamma-Aminobutyric acid|GABAergic]] synapses onto Purkinje cell dendrites.<ref name=SOB/>

===== Purkinje layer =====
[[File:PCP4 immunohistochemistry in human cerebellum.jpg|thumb|upright=0.8|Purkinje cells in the human cerebellum (in orange, from top to bottom 40X, 100X and 200X magnification) stained according to published methods<ref name="Felizola et al">{{cite journal | vauthors = Felizola SJ, Nakamura Y, Ono Y, Kitamura K, Kikuchi K, Onodera Y, Ise K, Takase K, Sugawara A, Hattangady N, Rainey WE, Satoh F, Sasano H | title = PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues | journal = Journal of Molecular Endocrinology | volume = 52 | issue = 2 | pages = 159–67 | date = April 2014 | pmid = 24403568 | pmc = 4103644 | doi = 10.1530/JME-13-0248 }}</ref>]]
[[Purkinje cell]]s are among the most distinctive neurons in the brain, and one of the earliest types to be recognized—they were first described by the Czech anatomist [[Jan Evangelista Purkyně]] in 1837. They are distinguished by the shape of their dendritic tree: the dendrites branch very profusely, but are severely flattened in a plane perpendicular to the cerebellar folds. Thus, the dendrites of a Purkinje cell form a dense planar net, through which parallel fibers pass at right angles.<ref name=SOB>{{cite book |title=The Synaptic Organization of the Brain | veditors = Shepherd GM |chapter=Ch. 7 ''Cerebellum'' |year=2004 |publisher=Oxford University Press |location=New York |isbn=978-0-19-515955-4 |vauthors=Llinas RR, Walton KD, Lang EJ }}</ref> The dendrites are covered with [[dendritic spine]]s, each of which receives synaptic input from a parallel fiber. Purkinje cells receive more synaptic inputs than any other type of cell in the brain—estimates of the number of spines on a single human Purkinje cell run as high as 200,000.<ref name=SOB/> The large, spherical cell bodies of Purkinje cells are packed into a narrow layer (one cell thick) of the cerebellar cortex, called the ''Purkinje layer''. After emitting collaterals that affect nearby parts of the cortex, their axons travel into the [[deep cerebellar nuclei]], where they make on the order of 1,000 contacts each with several types of nuclear cells, all within a small domain. Purkinje cells use [[GABA]] as their neurotransmitter, and therefore exert inhibitory effects on their targets.<ref name=SOB/>

Purkinje cells form the heart of the cerebellar circuit, and their large size and distinctive activity patterns have made it relatively easy to study their response patterns in behaving animals using [[extracellular field potential|extracellular]] recording techniques. Purkinje cells normally emit [[action potential]]s at a high rate even in the absence of the synaptic input. In awake, behaving animals, mean rates averaging around 40&nbsp;Hz are typical. The spike trains show a mixture of what are called simple and complex spikes. A simple spike is a single action potential followed by a [[Refractory period (physiology)|refractory period]] of about 10&nbsp;ms; a complex spike is a stereotyped sequence of action potentials with very short inter-spike intervals and declining amplitudes.<ref>{{cite journal | vauthors = Eccles JC, Llinás R, Sasaki K | title = The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum | journal = Journal of Physiology | volume = 182 | issue = 2 | pages = 268–96 | date = January 1966 | pmid = 5944665 | pmc = 1357472 | doi = 10.1113/jphysiol.1966.sp007824 }}</ref> Physiological studies have shown that complex spikes (which occur at baseline rates around 1&nbsp;Hz and never at rates much higher than 10&nbsp;Hz) are reliably associated with climbing fiber activation, while simple spikes are produced by a combination of baseline activity and parallel fiber input. Complex spikes are often followed by a pause of several hundred milliseconds during which simple spike activity is suppressed.<ref name=Simpson>{{cite journal |title=On climbing fiber signals and their consequence(s) |vauthors=Simpson JI, Wylie DR, De Zeeuw CI |journal=Behav. Brain Sci. |volume=19 |year=1996 |pages=384–398 |doi=10.1017/S0140525X00081486 |issue=3}}</ref>

A specific, recognizable feature of Purkinje neurons is the expression of [[calbindin]].<ref>{{cite journal | vauthors = Whitney ER, Kemper TL, Rosene DL, Bauman ML, Blatt GJ | title = Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: a stereological experiment | journal = Journal of Neuroscience Methods | volume = 168 | issue = 1 | pages = 42–7 | date = February 2008 | pmid = 17961663 | doi = 10.1016/j.jneumeth.2007.09.009 | s2cid = 10505177 }}</ref> Calbindin staining of rat brain after unilateral chronic sciatic nerve injury suggests that Purkinje neurons may be [[Adult neurogenesis|newly generated]] in the adult brain, initiating the organization of new cerebellar lobules.<ref name="ReferenceA">{{cite journal | vauthors = Rusanescu G, Mao J | title = Peripheral nerve injury induces adult brain neurogenesis and remodelling | journal = Journal of Cellular and Molecular Medicine | volume = 21 | issue = 2 | pages = 299–314 | date = February 2017 | pmid = 27665307 | pmc = 5264155 | doi = 10.1111/jcmm.12965 }}</ref>
[[File:3 recon 512x512.jpg|thumb|center|A mouse Purkinje cell injected with fluorescent dye]]
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===== Granular layer =====
[[File:Parallel-fibers.png|right|thumb|Granule cells (GR, bottom), parallel fibers (horizontal lines, top), and Purkinje cells (P, middle) with flattened dendritic trees]]
[[Cerebellar granule cell]]s, in contrast to Purkinje cells, are among the smallest neurons in the brain. They are also the most numerous neurons in the brain: In humans, estimates of their total number average around 50 billion, which means that about 3/4 of the brain's neurons are cerebellar granule cells.<ref name=SOB/> Their cell bodies are packed into a thick layer at the bottom of the cerebellar cortex. A granule cell emits only four to five dendrites, each of which ends in an enlargement called a ''dendritic claw''.<ref name=SOB/> These enlargements are sites of excitatory input from mossy fibers and inhibitory input from [[Golgi cell]]s.<ref name=SOB/>

The thin, [[myelin|unmyelinated]] axons of granule cells rise vertically to the upper (molecular) layer of the cortex, where they split in two, with each branch traveling horizontally to form a '''parallel fiber'''; the splitting of the vertical branch into two horizontal branches gives rise to a distinctive "T" shape. A human parallel fiber runs for an average of 3&nbsp;mm in each direction from the split, for a total length of about 6&nbsp;mm (about 1/10 of the total width of the cortical layer).<ref name=SOB/> As they run along, the parallel fibers pass through the dendritic trees of Purkinje cells, contacting one of every 3–5 that they pass, making a total of 80–100 synaptic connections with Purkinje cell dendritic spines.<ref name=SOB/> Granule cells use [[glutamic acid|glutamate]] as their neurotransmitter, and therefore exert excitatory effects on their targets.<ref name=SOB/>

[[File:Cerebellar glomerulus.tif|thumb|Diagram of the layers of the cerebellar cortex showing a [[Glomerulus (cerebellum)|glomerulus]] in the granular layer.]]
Granule cells receive all of their input from mossy fibers, but outnumber them by 200 to 1 (in humans). Thus, the information in the granule cell population activity state is the same as the information in the mossy fibers, but recoded in a much more expansive way. Because granule cells are so small and so densely packed, it is difficult to record their spike activity in behaving animals, so there is little data to use as a basis for theorizing. The most popular concept of their function was proposed in 1969 by [[David Marr (neuroscientist)|David Marr]], who suggested that they could encode combinations of mossy fiber inputs. The idea is that with each granule cell receiving input from only 4–5 mossy fibers, a granule cell would not respond if only a single one of its inputs were active, but would respond if more than one were active. This combinatorial coding scheme would potentially allow the cerebellum to make much finer distinctions between input patterns than the mossy fibers alone would permit.<ref name=Marr/>