Microscope view of a Purkinje cell Why the Purkinje Cell?
The Purkinje neuron is one of the most fascinating characters in the brain cell roster. The Purkinje and its supporting cast of mossy and climbing fibers, granular cells, and interneurons have been studied for decades, and the general shape of the Purkinje and its connections are pretty well known. Its circuitry, on the other hand, is a bit like the American Northwest before Lewis and Clarke. How the Purkinje operates on a network or systems level is still a mystery shrouded in the design of its structure and relationships. Yet without decoding the secret life of the Purkinje, neurobiologists will be unable to understand what the cerebellum does; and general principles about the whole brain will remain looming question marks.
From Journal of Neurophysiology, Vol. 71, No. 1 (January 1994), 375-400
"The cerebellar Purkinje cell is one of the largest and most complex neurons in the mammalian nervous system. Purkinje cells have very active dendrites, generating massive Ca2+ [calcium ion] signals in response to synaptic input . . . . Further, the unusual . . .anatomical organization of this cell's dendrite has been conserved to a remarkable degree through evolution, suggesting that this specific morphology is essential to the function of the Purkinje cell. In addition to its anatomical and physiological complexity and uniqueness, Purkinje cell activity also constitutes the sole output of the cerebellar cortex.
"While the precise computational role of the cerebellum is not yet known, it is clear that understanding the physiology of the Purkinje cell will be an essential part in unraveling the function of the cerebellar cortex as a whole. Given the complexity of this cell, we believe that computer modeling techniques are necessary to explore and analyze completely the properties of Purkinje cells." (Italics ours)
-- Erik De Schutter and James M. Bower
By neuronal standards Purkinjes are huge, with humongous cell bodies 80 microns in diameter, almost as big around as a human hair. A Purkinje is ten times as big as the smallest cerebellar neuron, the granular cell whose bodies are only around 6-8 microns in diameter. (Yet, there as almost as many of the tiny granular cells in the cerebellum as there are all types of neurons in the rest of the central nervous system -- combined!)
Purkinje Neurons As Cellular Composer
Purkinjes receive input from three brain cell fiber systems. One single Purkinje cell, for example, can receive converging input from over 200,000 other cells. Yet Purkinje cells are the sole output from the cerebellar cortex -- the convoluted, outer layer of the cerebellum that somewhat resembles the cerebral cortex. Any information exiting the cerebellum to the rest of the brain must go out from Purkinje cells. They are almost the only source of news, the sole tv network, the cerebellar state-controlled media.
Scientists have long marveled at the striking geometric patterns formed by the circuitry of the Purkinje and fellow neurons, the seeming remarkable regularity with which the different cells are wired together. Superficially at least, the arrangement presents more the logic of a Bach composition than the entangled Romantic works of the cerebrum. The stereotyped Purkinje wiring diagrams seem to present a relentless counterpoint to the rest of the brain.
Although many inputs to the Purkinje cell are from excitatory neurons --cells that fire chemical signals to other cells -- the Purkinje itself is an inhibitory neuron, meaning it selectively suppresses and limits excitatory impulses. Purkinje cells receive a tremendous amount of excitation through neurons from the spinal cord, cortex and other areas. All of these competing "voices" contribute to such a high level of background activity, the Purkinje cells are thought to sculpt or compose this "noise" (by virtue of their inhibition) into coherent "musical phrases" the rest of the brain can clearly understand.
Diagram of a cerebellar cross-section showing Purkinje cells in relation to layers of the cerebellum and to other neurons, including mossy and climbing fibers. What Neurons Deliver the News To the Purkinje Cells
Two kinds of neurons and neuronal fibers play commanding roles in bringing Purkinje cells word from the front.
- Mossy fibers come from the brain stem and spinal cord to influence Purkinje cells indirectly, by way of the tiny granule cells. As they ascend to meet Purkinje cells, the mossy fibers along with granule cells bifurcate and give rise to so-called "parallel fibers" that branch out in parallel "beams" to contact Purkinje cells in either direction. Each Purkinje cell receives converging input from about 200,000 of these parallel fibers. Nearly one million parallel fibers contact a human Purkinje cell. "On line," they create multitudes of small near-continuous firings. Parallel fibers might be seen as the ubiquitous telephone lines that crisscross any neighborhood, always humming.
- Climbing fibers originate in brain stem areas called medulla oblongata and inferior olivary nucleus. Unlike parallel fibers, climbing fibers go one-on-one with Purkinje cells, contacting only a few. Each Purkinje cell receives synaptic input from only one single climbing fiber. The climbing fiber literally wraps itself around the body and dendrites of the Purkinje cell, making many synaptic contacts. From this intense embrace arises one of the most powerful connections in the entire nervous system. This massive neurochemical intercourse results in what is called a "complex spike," a huge electrical firing event. Some think the complex spike happens when the Purkinje complex is noting something new and marking it for memory storage.
Thus the Purkinje receive at least two different pulses of information occurring in a kind of syncopated rhythm: simple spiking coming from a "promiscuous" interaction of parallel fibers; and a complex spike from the "monogamous" climbing fibers -- all conveying information from different regions of the brain.
For a long time scientists thought that was it. But in the Bower lab, investigator John Thompson tells us that the little known "inhibitory interneurons" -- the golgi cells, the stellate and basket cells -- are also involved in some sort of feedback system. A golgi cell can shut down a region of granule cells; basket cells can shut down or alter Purkinje cells; stellate cells can shut down or alter conductances up in the dendrites (long arms) of the Purkinje cells. "The structures that looked like crystal," comments John Thompson, "where you say `Oh wow, these Purkinje cells sitting there in their planar fashion like telephone poles with wires running through them!' -- When you start adding more detail, it gets more complicated."
What The Purkinje Cells Do (Or a Hundred Thousand Hourglasses)
There are lots of theories out there. David Marr presented one of the first in the late Sixties. The Marr-[James] Albus theory says, basically, that Purkinjes are timers. They sit on the parallel fibers and pick off the incoming impulses at certain times. Added to that theory now is a kind of "tidal wave" hypothesis: A wave of impulses surges down the parallel fibers and each Purkinje cell fires consecutively as the impulse gets to it. The Purkinje output, then, is involved with timing of neuromuscular events and sensation -- where a body is in space at any given moment.
Some people in the Bower Lab think the parallel fibers bring contextual information to the cerebellum, telling the Purkinje cells subtle things about what one body part is doing in relation to another.
For more about that, see Loco Motion.
--Kathleen Stein
