The dynamics of interneuronal communication in the brain
The theme of Mind and Brain is helping to unravel consciousness from the cell to self and personal identity.
By demonstrating novel dynamic processes in individual neurons, a research team at the University of Sussex are 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.
The discovery of the sharing of a ‘super-pool’ of vesicles between neuronal synapses sheds light on the dynamic process of intercellular communication in the brain
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.
Studying interneuronal communication
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.
Arjuna’s perspective
Dr Arjuna Ratnayaka, Research Fellow School of Life Sciences, said: "It’s really exciting to be part of a field that is challenging our fundamental understanding of the way the nervous system works.
"It’s particularly appealing because we address these issues using state-of-the-art imaging methods that allow us to actually observe cellular events.
"For a visual person, there’s something really satisfying about directly seeing the dynamic processes taking place in neurons to support information transmission around the brain.
"The trick with this kind of work is to be really innovative in designing experiments: keeping a close eye on new optical imaging techniques and then exploiting these developments to provide novel insights into brain function.
"The strength of neuroscience work at Sussex provides a great backdrop for our research. For example, major groups with interests in fundamental disease mechanisms and learning and memory offer genuine opportunities for collaborative projects, expanding our own research into new areas.
"Ultimately, we hope that the combination of approaches we use and the synergy between us and other groups at the University might even offer novel therapeutic targets for tackling diseases of the nervous system."