Bruger:Christian89/projekter

Purkinje celler eller Purkinje neuroner er en type af GABAerge neuroner lokaliseret i lillehjernen. De er opkaldt efter deres tjekkiske opdager Jan Evangelista Purkyně.

Anatomi

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

Purkinje cells. Bielschowsky stain.

Purkinje celler er nogle af de største celler i menneskehjenen (med Betz celler som de største) indviklet detaljeret dendrittræ som er karakteriseret ved det store antal af dendritiske fremskud (en: Spines). Purkinje cellerne forekommer i lillehjernens såkaldte Purkinje lag.

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 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. 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.

Elektrofysiologi

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 celler har to forskellige former for elektrofysiologisk aktivitet:

• 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.

• Complekse 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.

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.

The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump. 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. Furthermore, using the poison ouabain to block Na⁺-K⁺ pumps in the cerebellum of a live mouse induces ataxia and dystonia.