By demonstrating novel dynamic processes in individual neurons, a research team at the University of Sussex is helping to understand how cells might adjust their communication properties to support the flexible output of the nervous system and even learning and memory formation.
In recent years, an increasing body of evidence has shown that many functions of the brain are highly dynamic, or ‘plastic’, ie that the brain is able to continually change in response to stimulus and experience. This flexibility is thought to be a key property in allowing the nervous system to support short-term and sustained changes in output, associated with learning and memory. However, the mechanisms that underlie this flexibility are not well understood. Chemical synapses are key sites in the nervous system, existing as junctions between neurons that allow the transmission of information from one cell to another within complex neuronal networks. Using innovative microscopic imaging technologies, researchers in the School of Life Sciences at the University of Sussex are studying neurons in the hippocampus. By uncovering novel aspects of synapse–synapse interaction, they propose that these properties may underlie dynamic capabilities in brain function.
The hippocampus, the part of the brain thought to be critical to learning and memory, provides a standard model for studying interneuronal communication, how the transmission of information can change, and how alterations in the ‘strength’ of the signal are transmitted at synaptic junctions. Synapses comprise a presynaptic and postsynaptic terminal on neuronal axons that are separated by an extracellular space. Any single presynaptic terminal can contain several hundreds or thousands of synaptic vesicles filled with neurotransmitter. Information is transmitted across the synapse by vesicles in the presynaptic terminal fusing with the cell membrane and releasing the neurotransmitter into the extracellular space, where it is ‘taken up’ by the postsynaptic terminal. Vesicles in the presynaptic terminal are then reclaimed from the cell membrane back into the cell through a process called endocytosis to permit further signalling events to take place. Through understanding the extent and timing of this process, and the mechanisms underlying vesicle recycling and changing ‘strength’ of the synaptic signal, it may be possible to better understand the processes of learning and memory.
Recently published work from a research group at Sussex, led by Dr Kevin Staras, Reader in Neuroscience, has demonstrated that the process of vesicle recycling may be more dynamic and complex than originally thought. Synaptic terminals within any neuron do not exist as single operational entities but are part of a much larger population, with hundreds or even thousands of terminals in a single neuron forming connections with other neuronal targets.
Using powerful cutting-edge fluorescencebased imaging and correlative light-electron microscope techniques, the Sussex team has been the first to show that, rather than these synaptic populations working independently of each other, vesicles form part of a shared ‘super-pool’ that can be transferred between the presynaptic terminals of a single neuron at a substantial rate. This trading of vesicles between synapses is potentially very important. For example, given that the strength of the synapse is directly related to the number of vesicles it contains, a mechanism by which synapses can draw from an extrasynaptic pool and increase their vesicle number offers a potential mechanism to dynamically adjust synaptic strength.
If this process is shown to underlie a capability for neurons to be flexible in their signalling function, it could offer insights into disease conditions where this flexibility may be severely compromised, thereby offering potential new therapeutic targets for combating neuronal dysfunction.
Extracted from the 2011 Research Review.