Purkinje cells

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

Anatomy

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

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 - 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 - pumps in the cerebellum of a live mouse induces ataxia and dystonia.^[8]

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.^[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

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 to 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

External links

• Cell Centered Database - Purkinje
• Disorders of cerebellum
• Neuroscience Information Framework

Further reading