Purkinje cell

Purkinje cell

Drawing of pigeon Purkinje cells (A) by Santiago Ramon y Cajal
Location Cerebellum
Morphology flat dendritic arbor
Function inhibitory projection neuron
Neurotransmitter GABA
Presynaptic connections Parallel fibers and Climbing fibers
Postsynaptic connections Cerebellar deep nuclei
NeuroLex ID Purkinje Cell
TA A14.1.07.404
FMA 83896

Anatomical terminology

Purkinje cells, or Purkinje neurons (/pərˈkɪn/ pər-KIN-jee), are a class of GABAergic neurons located in the cerebellum. They are named after their discoverer, Czech anatomist Jan Evangelista Purkyně (Czech: [ˈpurkɪɲɛ]).


Transverse section of a cerebellar folium. (Purkinje Cell labeled at center top.)
Purkinje cells. Bielschowsky stain.

These cells are some of the largest neurons in the human brain (Betz cells being the largest),[1] with an intricately elaborate dendritic arbor, characterized by a large number of dendritic spines. Purkinje cells are found within the Purkinje layer in the cerebellum. Purkinje cells are aligned like dominos stacked one in front of the other. Their large dendritic arbors form nearly two-dimensional layers through which parallel fibers from the deeper-layers pass. These parallel fibers make relatively weaker excitatory (glutamatergic) synapses to spines in the Purkinje cell dendrite, whereas climbing fibers originating from the inferior olivary nucleus in the medulla provide very powerful excitatory input to the proximal dendrites and cell soma. Parallel fibers pass orthogonally through the Purkinje neuron's dendritic arbor, with up to 200,000 parallel fibers[2] forming a Granule-cell-Purkinje-cell synapse with a single Purkinje cell. Each Purkinje cell receives ca 500 climbing fiber synapses, all originating from a single climbing fiber.[3] Both basket and stellate cells (found in the cerebellar molecular layer) provide inhibitory (GABAergic) input to the Purkinje cell, with basket cells synapsing on the Purkinje cell axon initial segment and stellate cells onto the dendrites.

Purkinje cells send inhibitory projections to the deep cerebellar nuclei, and constitute the sole output of all motor coordination in the cerebellar cortex.


There is evidence in mice and humans that bone marrow cells either fuse with or generate cerebellar Purkinje cells, and it is possible that bone marrow cells, either by direct generation or by cell fusion, could play a role in repair of central nervous system damage.[4][5][6][7][8] Further evidence points yet towards the possibility of a common stem cell ancestor among Purkinje neurons, B-lymphocytes and aldosterone-producing cells of the human adrenal.[7]

Electrophysiological activity

Microcircuitry of the cerebellum. Excitatory synapses are denoted by (+) and inhibitory synapses by (-).
MF: Mossy fiber.
DCN: Deep cerebellar nuclei.
IO: Inferior olive.
CF: Climbing fiber.
GC: Granule cell.
PF: Parallel fiber.
PC: Purkinje cell.
GgC: Golgi cell.
SC: Stellate cell.
BC: Basket cell.

Purkinje cells show two distinct forms of electrophysiological activity:

The Purkinje cell protein 4 (PCP4) is markedly immunoreactive in the Purkinje cells of the human cerebellum. From top to bottom 40X, 100X and 200X microscopic magnifications. The immunohistochemistry was performed based on published methods.[10]

Purkinje cells show spontaneous electrophysiological activity in the form of trains of spikes both sodium-dependent and calcium-dependent. This was initially shown by Rodolfo Llinas (Llinas and Hess (1977) and Llinas and Sugimori (1980)). P-type calcium channels were named after Purkinje cells, where they were initially encountered (Llinas et al. 1989), which are crucial in cerebellar function. We now know that activation of the Purkinje cell by climbing fibers can shift its activity from a quiet state to a spontaneously active state and vice versa, serving as a kind of toggle switch.[11] These findings have been challenged by a study suggesting that such toggling by climbing-fiber inputs occurs predominantly in anaesthetized animals and that Purkinje cells in awake behaving animals, in general, operate almost continuously in the upstate.[12] But this latter study has itself been challenged [13] and Purkinje cell toggling has since been observed in awake cats.[14] A computational model of the Purkinje cell has shown intracellular calcium computations to be responsible for toggling.[15]

Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses.[16] The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump.[17] This suggests that the pump might not be simply a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the cerebellum and the brain.[18] Indeed, a mutation in the Na+
pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation.[19] Furthermore, using the poison ouabain to block Na+
pumps in the cerebellum of a live mouse induces ataxia and dystonia.[20] Numerical modeling of experimental data suggests that, in vivo, the Na+
pump produces long quiescent punctuations (>> 1 s) to Purkinje neuron firing; these may have a computational role.[21] Alcohol inhibits Na+
pumps in the cerebellum and this is likely how it corrupts cerebellar computation and body co-ordination.[22][23]

Molecular profile

The Purkinje layer of the cerebellum, which contains the cell bodies of the Purkinje cells and Bergmann glia, express a large number of unique genes.[24] Purkinje-specific gene markers were also proposed by comparing the transcriptome of Purkinje-deficient mice with that of wild-type mice.[25] One illustrative example is the Purkinje cell protein 4 (PCP4) in knockout mice, which exhibit impaired locomotor learning and markedly altered synaptic plasticity in Purkinje neurons.[10][26] PCP4 accelerates both the association and dissociation of calcium (Ca2+) with calmodulin (CaM) in the cytoplasm of Purkinje cells, and its absence impairs the physiology of these neurons.[10][26][27][28]

In humans, Purkinje cells can be harmed by a variety causes: toxic exposure, e.g. to alcohol or lithium; autoimmune diseases; genetic mutations causing spinocerebellar ataxias, Unverricht-Lundborg disease, or autism; and neurodegenerative diseases that are not known to have a genetic basis, such as the cerebellar type of multiple system atrophy or sporadic ataxias.

Some domestic animals can develop a condition where the Purkinje cells begin to atrophy shortly after birth, called cerebellar abiotrophy. It can lead to symptoms such as ataxia, intention tremors, hyperreactivity, lack of menace reflex, stiff or high-stepping gait, apparent lack of awareness of foot position (sometimes standing or walking with a foot knuckled over), and a general inability to determine space and distance.[29] A similar condition known as cerebellar hypoplasia occurs when Purkinje cells fail to develop in utero or die off before birth.

The genetic conditions ataxia telangiectasia and Niemann Pick disease type C, as well as cerebellar essential tremor, involve the progressive loss of Purkinje cells. In Alzheimer's disease, spinal pathology is sometimes seen, as well as loss of dendritic branches of the Purkinje cells.[30] Purkinje cells can also be damaged by the rabies virus as it migrates from the site of infection in the periphery to the central nervous system.[31]


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  26. 1 2 Wei P, Blundon JA, Rong Y, Zakharenko SS, Morgan JI (2011). "Impaired locomotor learning and altered cerebellar synaptic plasticity in pep-19/PCP4-null mice". Mol. Cell. Biol. 31 (14): 2838–44. doi:10.1128/MCB.05208-11. PMC 3133400Freely accessible. PMID 21576365.
  27. Putkey JA, Kleerekoper Q, Gaertner TR, Waxham MN (2004). "A new role for IQ motif proteins in regulating calmodulin function.". J. Biol. Chem. 278 (50): 49667–70. doi:10.1074/jbc.C300372200. PMID 14551202.
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  29. For references, see the extensive references and bibliography at the article on Cerebellar abiotrophy, linked at the beginning of this paragraph.
  30. Mavroudis, IA; Fotiou, DF; Adipepe, LF; Manani, MG; Njau, SD; Psaroulis, D; Costa, VG; Baloyannis, SJ (November 2010). "Morphological changes of the human purkinje cells and deposition of neuritic plaques and neurofibrillary tangles on the cerebellar cortex of Alzheimer's disease". American Journal of Alzheimer's Disease & Other Dementias. 25 (7): 585–91. doi:10.1177/1533317510382892. PMID 20870670.
  31. Fekadu, Makonnen (27 March 2009). "Rabies encephalitis, Negri bodies within the cytoplasm of cerebellar Purkinje cell neurons". CDC/Frontal Cortex Inc. Retrieved 21 June 2013. Note: not peer-reviewed.

Further reading

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