The Hum Or Bursts Of Purkinje Cells

The two different states of Purkinje cell signaling could be related to how the cell decides to respond to incoming signals, scientists say.

AsianScientist (Oct. 13, 2015) – In a study published in eLife, Ms. Mohini Sengupta and Dr. Vatsala Thirumalai from the National Center for Biological Sciences (NCBS), Bangalore, have found that Purkinje cells can send out electrical signals in either a constant hum or in sudden bursts, depending on the voltage across their cell membranes and on inputs from a specific region of the brain.

The cerebellum is a small leaf-like structure at the base of our brain that is important for controlling balance, coordination and for learning new motor skills such as riding a bicycle or playing a piano. Nerve cells named Purkinje cells are arranged neatly in a single layer within the cerebellum and are essential in carrying out the aforementioned functions. Purkinje cells receive signals from many different regions of the brain and send out messages to the deeper layers of the cerebellum.

How Purkinje cells communicate with other nerve cells, has thus far been a mystery, mainly because it is difficult to ‘listen’ to these cells in animals that are awake and moving around. Purkinje cells are very small and scientists employ very fine instruments to record their electrical signals in experiments that require animals to be anesthetized, as even small movements can knock the equipment out of place.

Unfortunately, the anesthetics themselves can alter the electrical signals generated by the brain. Therefore, previous studies on the signals generated by Purkinje cells in awake and moving animals have been inconclusive.

The team at NCBS circumvented these issues by carrying out their research on the diminutive zebrafish, a fresh water fish found in the Ganga and Brahmaputra. The young of the zebrafish are transparent and have not yet developed a skull. Furthermore, specific nerve cells in these fish can be made to glow by injecting DNA into them. This made it possible for scientists to insert and precisely place fine recording equipment onto the Purkinje cells within the fish brains.

To prevent the fish from moving, a paralytic agent that does not interfere with electrical signals in the brain was used. This combination of techniques allowed researchers to record electrical signals from Purkinje cells in an animal that was not anesthetized.

Results from these experiments showed that Purkinje cells send out electrical signals in two different modes depending on the voltage at their cell surfaces. The first mode, called the ‘down’ state, occurred when the inside of the cell was more negative compared to the outside. In this state, cells were silent until signals from a different part of the brain arrived, at which time, they sent out a burst of impulses.

In the second mode, called the ‘up’ state, the inside of the cell was less negative compared to the outside and Purkinje cells sent out impulses at a constant rate. In this mode, these cells ignored any impulses coming from other parts of the brain. These states are reminiscent of a person attentively listening to directions and responding accordingly, or simply ‘zoning out’ and going their own way irrespective of instructions.

What does this phenomenon mean for the functioning of the cerebellum? To understand this, the researchers recorded the instructions sent out by the nervous system to muscles. Their results indicate that Purkinje cells receive a copy of the instructions sent to muscles and that they generate a burst of impulses in response.

The researchers propose that the existence of the ‘up’ and ‘down’ states could be a mechanism by which Purkinje cells ‘choose’ to listen in on such instructions or not. What do these cells do with the instruction copy? Do they alter their signals when the animal is learning new motor tasks? The authors hope to find out answers to these questions in ongoing experiments.

The article can be found at: Sengupta and Thirumalai (2015) AMPA Receptor Mediated Synaptic Excitation Drives State-Dependent Bursting in Purkinje Neurons of Zebrafish Larvae.


Source: Tata Institute of Fundamental Research.
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