Two studies featuring research from Weill Cornell Medical College have uncovered details have uncovered surprising details about the complex process that leads to the flow of neurotransmitters between brain neurons — a dance of chemical messages so delicate that missteps often lead to neurological dysfunctions, such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and other neurodegenerative and psychiatric disorders.

Speed of vesicle recovery
The first study was designed to look at what controlled the speed of the vesicle recovery process. This speed, which dictates the availability of vesicles, has long been considered to be one of the limits as to how fast neurons can continuously communicate, especially in high-demand situations, the researchers said.

To study the speed of this recovery process, the researchers used a tool that took optical recordings of the speed of vesicle recycling across 84 different neurons.They found that an individual neuron retrieves all of its synaptic vesicles at pretty much the same speed.

Proteins involved in vesicle recovery
The second study looked at proteins involved in one phase of the recovery process of synaptic vesicles (which are in limited supply, and must be retrieved, rebuilt and refilled with neurotransmitters). This involved separating and pinching off the membrane of the synaptic vesicle from the membrane of the neuronal cell. The researchers believe that a protein called dynamin, which comes in three forms (1, 2 and 3), was critical to this “membrane fission” step in the formation of vesicles.

The researchers looked at what happened when both dynamin 1 and dynamin 3, which make up 99 percent of dynamin protein, are missing. They used the same optical methods employed in the first study. They showed that retrieval is severely impaired when you have neither dynamin 1 nor dynamin 3, demonstrating that dynamin 3 has a major presynaptic function.

“Many neurological diseases such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and other neurodegenerative and psychiatric disorders are considered to be synaptopathies — pathologies of synaptic function. So repairing them will require that we understand how they work,” said Dr. Timothy Ryan.

Ref.: Moritz Armbruster, Timothy A Ryan, Synaptic vesicle retrieval time is a cell-wide rather than individual-synapse property, Nature Neuroscience, 2011; [DOI: 10.1038/nn.2828]

Ref.: Valentina Cappello et al., Overlapping Role of Dynamin Isoforms in Synaptic Vesicle Endocytosis, Neuron, Volume 70, Issue 6, 1100-1114, 23 June 2011 [DOI: 10.1016/j.neuron.2011.04.031]