Purkinje cell

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Neuron: Purkinje cell
PurkinjeCell.jpg
Drawing of pigeon Purkinje cells (A) by Santiago Ramon y Cajal
Location Cerebellum
Function inhibitory projection neuron
Neurotransmitter GABA
Morphology flat dendritc arbor
Presynaptic connections Parallel fibers and Climbing fibers
Postsynaptic connections Cerebellar deep nuclei
NeuroLex ID sao471801888

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]).

Anatomy[edit]

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.

Electrophysiological activity[edit]

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:

  • Simple spikes occur at rates of 17 – 150 Hz (Raman and Bean, 1999), either spontaneously or when Purkinje cells are activated synaptically by the parallel fibers, the axons of the granule cells.
  • Complex spikes are slow, 1–3 Hz spikes, characterized by an initial prolonged large-amplitude spike, followed by a high-frequency burst of smaller-amplitude action potentials. They are caused by climbing fiber activation and can involve the generation of calcium-mediated action potentials in the dendrites. Following complex spike activity, simple spikes can be suppressed by the powerful complex spike input.[4]

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 (Loewenstein et al., 2005, Nature Neuroscience). However, these findings have recently 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 (Schonewille et al., 2006, Nature Neuroscience).

Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses.[5]

The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump.[6] 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. Indeed, a mutation in the Na+
-K+
pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation.[7] Furthermore, using the poison ouabain to block Na+
-K+
pumps in the cerebellum of a live mouse induces ataxia and dystonia.[8]

Molecular profile[edit]

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.[9] Purkinje-specific gene markers were also proposed by comparing the transcriptome of Purkinje-deficient mice with that of wild-type mice.[10]

Medical conditions related to Purkinje cells[edit]

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.[11] 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, we sometimes see spinal pathology as well as loss of dendritic branches of the Purkinje cells.[12] 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 [13]

References[edit]

  1. ^ Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 432–4. ISBN 978-0-87893-697-7. 
  2. ^ Tyrrell, T; Willshaw, D (1992-05-29). "Cerebellar cortex: its simulation and the relevance of Marr's theory.". Philosophical transactions of the Royal Society of London. Series B, Biological sciences 336 (1277): 239–57. doi:10.1098/rstb.1992.0059. PMID 1353267. 
  3. ^ Wadiche, JI; Jahr, CE (2001-10-25). "Multivesicular release at climbing fiber-Purkinje cell synapses". Neuron 32 (2): 301–13. doi:10.1016/S0896-6273(01)00488-3. PMID 11683999. 
  4. ^ Eric R. Kandel, James H. Schwartz, Thomas M. Jessell (2000). Principles of Neural Science. 4/e. McGraw-Hill. pp.837-40.
  5. ^ Kreitzer AC, Regehr WG (March 2001). "Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells". Neuron 29 (3): 717–27. doi:10.1016/S0896-6273(01)00246-X. PMID 11301030. 
  6. ^ Forrest MD, Wall MJ, Press DA, Feng J (December 2012). "The Sodium-Potassium Pump Controls the Intrinsic Firing of the Cerebellar Purkinje Neuron". In Cymbalyuk, Gennady. PLoS ONE 7 (12): e51169. doi:10.1371/journal.pone.0051169. PMC 3527461. PMID 23284664. 
  7. ^ Cannon C (July 2004). "Paying the Price at the Pump: Dystonia from Mutations in a Na+/K+-ATPase". Neuron 43 (2): 153–154. doi:10.1016/j.neuron.2004.07.002. PMID 15260948. 
  8. ^ Calderon DP, Fremont R, Kraenzlin F, Khodakhah K (March 2011). "The neural substrates of rapid-onset Dystonia-Parkinsonism". Nature Neuroscience 14 (3): 357–65. doi:10.1038/nn.2753. PMC 3430603. PMID 21297628. 
  9. ^ Kirsch, L; Liscovitch, N, Chechik, G (December 2012). "Localizing Genes to Cerebellar Layers by Classifying ISH Images". In Ohler, Uwe. Public library of Science - computational biology 8 (12): e1002790. doi:10.1371/journal.pcbi.1002790. PMC 3527225. PMID 23284274. 
  10. ^ Rong, Y; Wang T; Morgan J (2004). "Identification of candidate purkinje cell-specific markers by gene expression profiling in wild-type and pcd3j mice". Molecular brain research 13 (2): 128–145. doi:10.1016/j.molbrainres.2004.10.015. 
  11. ^ For references, see the extensive references and bibliography at the article on Cerebellar abiotrophy, linked at the beginning of this paragraph.
  12. ^ 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 and other dementias 25 (7): 585–91. doi:10.1177/1533317510382892. PMID 20870670. 
  13. ^ 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.

External links[edit]

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