Synaptic transmission is plastic

So, what do we mean by the phrase 'synaptic transmission is plastic'? Well, if something is plastic, it means that it can be moulded and changed. A lump of plastercine (or play-dough) can be transformed into what ever shape we want. It does not have fixed properties and can change. Try clicking on the picture to see what I mean.

Thus the phrase 'synaptic transmission is plastic' means that the post-synaptic response to the release of neurotransmitter is not necessarily always the same. For example, the post-synaptic response may be made stronger or weaker for a short while.....or for a long time. The ability for something to change is termed plasticity and plasticity at synapses is termed synaptic plasticity. The mechanisms that bring this phenomenon about and the functions it plays in normal and pathological states underlie the research of the MRC Centre for Synaptic Plasticity.

Why is synaptic plasticity important?

The brain is plastic throughout life - it is constantly changing. The ability to learn and form memories, things that we take so much for granted, comes about because of the ability of neurons to change the way in which they communicate with each other - that is, through synaptic plasticity. One of the greatest challenges in neuroscience is to determine how synaptic plasticity and learning and memory are linked. Such insights are essential in order to understand the nature of diseases that affect memory systems such as Alzheimer's disease and demetias.

In addition to roles in learning, synaptic plasticity is crucial for the physical building of our brains during development and throughout the rest of our lives. The circuits in our brains that allow us to experience the world via our senses, to move and probably to think are built through a process of synapse formation and removal. Synapses that are active and actively changing are kept, the rest are 'pruned'. Thus, the neuronal circuits needed to move the appropriate muscles that allow us to walk and talk are created in infancy through use to become permanent features of our brains. However, if those circuits are damaged through a stroke, for instance, they can be re-built through a process of learning (especially in children), demonstrating the amazing recuperative abilities of the brain. Part of the work of the Centre is aimed at understanding the role glutamate receptors play in the damaging effects of neurosteroids on the brains of very premature infants.

Synaptic plasticity comes in many flavours too!!

So we have established that neuronal communication is plastic. But how plastic is plastic? In the case of neurons - very plastic indeed!!! The post-synaptic response to stimulation (the 'synaptic strength' or 'synaptic weight') can be modulated in the short term (i.e. for hundreds of milliseconds) or for the long term (hours, days or even weeks!!). Synaptic strength is increased or decreased by altering the level of post-synaptic depolarisation. This is achieved through changing how well receptors respond to stimulation by altering the length of time they are active, the number of receptors physically present or by altering the amount of L-glutamate that is released into the the synaptic cleft.

Synaptic strength can be increased

Long term potentiation (LTP) is a long term increase in synaptic strength. It was discovered in the early 1970's in a region of the brain called the dentate gyrus, part of the hippocampal formation. This structure is known to be involved in many aspects of spatial learning and memory formation and although LTP was discovered in this structure, it has since been shown to be a common feature of neuronal communication throughout the brain.

LTP is induced by a train of high frequency stimulation, a tetanus, similar to the kind of stimulation neurons receive during intense activity (e.g. learning a new task). However, it is not a single process, rather a term to cover a range of different mechanisms that result in the same outcome. One of the most widely studied forms of LTP is known as NMDA receptor-dependent LTP. This form of LTP requires the activation of NMDA receptors, allowing an influx of calcium ions into the post-synaptic cell. Work within the Centre for Synaptic Plasticity, using a technique known as non-stationary fluctuation analysis, has suggested that NMDA receptor-dependent LTP may result from the ability of post-synaptic AMPA receptors to pass more current (ie to be open longer). This is likely to be the result of a modification of the receptors, such as phosphorylation . A second mechanism by which NMDA receptor-dependent LTP may be expresed is from an increased number of AMPA receptors expressed on the post-synaptic cell surface.

Synaptic strength can also be decreased

In addition to LTP, synaptic strength can also be decreased, long term depression (LTD), a process induced by a train of low frequency stimuli.

LTD, like LTP, is not a single process. There are multiple forms of LTD expressed in different brain regions. One form of LTD is again dependent on NMDA receptor activation. Non-stationary fluctuation analysis suggests that the mechanism underlying NMDA receptor-dependent LTD does not involve a reduction in the current passed by AMPA receptors but rather a reduction in the number of AMPA receptors expressed on the post-synaptic cell surface. Indeed, the number of AMPA receptors can be reduced to the point where the synapses no longer responds to stimulation - it has been 'silenced'. suggests that the mechanism underlying NMDA receptor-dependent LTD does not involve a reduction in the current passed by AMPA receptors but rather a reduction in the number of AMPA receptors expressed on the post-synaptic cell surface. Indeed, the number of AMPA receptors can be reduced to the point where the synapses no longer responds to stimulation - it has been 'silenced'.

Two other forms of LTD have recently been discovered through work at the Centre for Synaptic Plasticity that involve activation of metabotropic glutamate receptors. The mechanisms underlying these phenomena are currently unclear.

Synapses can undergo both LTP and LTD

The functioning of synapses can be regulated either up or down i.e. synapses are bi-directionally modifiable. Whether a synapse undergoes LTP or LTD depends on the previous history of that synapse, the type of stimulation it receives and the immediate environment it is in. This results in an incredibly flexible system with which to deal with the mish-mash of information the brain receives every second of every day.

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