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The Key to Comminication

Synaptic Physiology

Where do you meet your friend for a chat? Do you go to a coffee shop? Maybe an after-work refreshment at the pub? Or maybe you just pop on whatsapp to have a cyber catch-up? Whereas you and your mates can choose where to have a chin wag, your neurons are always chatting to each other at one place; the synapse. The synapse is the junction between two neurons and allows one cell to pass on a message to another. But synapses don’t listen to any old drivel; only important messages are transmitted to the receiving cell and this filtering is all modulated by chemicals. A neuron can receive signals from thousands of synapses at once, so it is important only the most important messages are communicated. So, let’s read on to zoom in on the Starbucks of the central nervous system and learn a bit more about the ingredients required to make a perfect blend for signal transmission.

How receptive are you? The Dynamics of Chemicals and Receptors at the Synapse

A synapse is made up of two parts; a pre-synaptic and a post-synaptic terminal.   The pre-synaptic terminal is found at the end of a signalling axon and the post-synaptic terminal is on the dendrite of the receiving neuron. In between these two terminals is a space called the synaptic cleft where the physical part of signal transmission happens. This space gets filled with different chemicals when a signal reaches the end of an axon and these chemicals can promote or prevent a signal being passed on.

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The pre-synaptic terminal is filled with many small compartments called vesicles packed with chemicals. A lot of these vesicles are docked on the pre-synaptic terminal; ready for their release. When a large signal travels down the axon, the packed vesicles fuse with the pre-synaptic terminal membrane, leading to a rapid flooding of chemicals into the synaptic cleft. These chemicals bind to proteins called receptors on the post-synaptic terminal and allow the dendrite of the accepting neuron to receive the signal.

Think of the chemicals as gate keepers and the receptors as gates. The gate keepers are required to open the gates to allow the message to pass through to the next neuron. However, each gate keeper can only hold open a gate for a limited period of time; preventing signal transmission if only a few gate-keepers are working shift. The number of workers on shift is determined by the scale of the signal from the delivering axon. If a small signal reaches the pre-synaptic terminal, only a few gate-keepers are released to open the gates as transmission of this minor message is probably not vital. However, if a large signal arrives from the axon, many gate-keepers are released at once; meaning when one lets go of the gate, another is there to hold it open. Even when a large signal is received, the gate-keepers still ‘clock off’ shift and are removed from the synaptic cleft. This allows the gates to be closed and the signalling to stop; meaning any new signals from the axon can be transmitted independently from previous ones.

 

So to put all that gate-keeping biznisss into neuroscience talk, the number of vesicles that fuse with the pre-synaptic membrane is dependent on the amplitude of the signal from the axon. Therefore, small signals lead to less chemicals in the synaptic cleft, less binding to post-synaptic receptors and less chance of the signal being passed on. This prevents ‘non-important’ signals or accidental vesicle fusion causing a full-on signal cascade to the post-synaptic neuron. Large signals lead to saturating levels of chemicals being released into the cleft, ensuring receptors stay open long enough to pass on the signal. However, it is super important that this signal transmission is stopped, otherwise no other signals could be sent at this synapse. So, the chemicals are cleared from the synaptic cleft by enzymes and the receptors are closed.

Taking the negative with the positive: Ions and Action potentials

Now we all are experts in how a signal is passed from one neuron to another at a synapse, let us get a bit more nitty-gritty with the deets of signal transmission. As mentioned in a previous post all about neurons, the signals sent down the axon are called action potentials. Action potentials are all-or-none, meaning there is no ‘small’, ‘quite big’ or ‘super huge’ action potential; they are all the same size. It is the frequency of these signals which signifies their size, with many action potentials being regarded as a v important message.

 

But what is an action potential? It is not like the mystery waves we picture when we think of how Wi-Fi works or how your phone can send a text (aba 2 a month these days) to another phone. An action potential involves physical particles inside and outside the neuron changing places. These ions are vital to neuron (and your) survival and you may have heard about them when people talk about salt and bananas. Any guesses?

That’s right. Action potentials are mediated by sodium and potassium; small positively charged ions whose balance is fundamental to neuron communication. Inside every neuron, they are high levels of potassium and low levels of sodium and outside the neurons, the reverse is true. As these ions are charged, they cannot cross the neuron’s membrane. The only way they can move is through channels which open and close according to neuron membrane (DANGER DANGER, HIGH) voltage. When a sodium channel opens, sodium ions flow in to the neuron to increase their numbers inside the cell. Potassium ions flow out of the neuron when potassium channels open because they want to increase their numbers outside the neuron. This attempt to balance is called equilibrium; the process every ion strives to be at in the atmosphere.

 

The neurons resting membrane voltage (potential) is -70 millivolts (mV) and as a few sodium ion channels open, this voltage slowly creeps up to a more positive value. Once a membrane voltage of around -45mV is reached, all the sodium channels in the near vicinity open; causing a huge influx of positive sodium, driving the neuron membrane potential up to +40mV. As this voltage becomes more positive, sodium channels close and potassium channels open, allowing the potassium ions flood out the neuron. This drives the high membrane potential all the way down to -85mV; creating a very small ‘refractory period’. This means that if another signal was activated during this time, no action potential could be initiated as the membrane is too negative to activate sodium channel opening. This refractory period is superrrr important in distinguishing signals as isolated events. Otherwise, proceeding signals could get mixed into the current signal and generate a whole signalling failure (we all know how horrendous they are fellow commuting Londoners).

The diagram of an action potential above gives a lil summary. The y-axis marks the voltage of the neuron membrane and the x-axis is time. The annotations show you when sodium ions are coming in and potassium ions are coming out. Each ion has individual, specific channels which only lets that ion through, so no ions can shimmy their way through another ion’s channel. Once the action potential has occurred, special pumps in the membrane put the sodium and potassium ions back to their normal locations so when another signal needs to be sent, these ions are ‘pumped’ and ready to go (jokes getting worse the more I blog).

Promoting Inhibitions: How receptors and ions work together at the synapse

Now let’s put information about the receptors at synapse and action potentials together to understand how a signal is passed from one neuron to the next. The chemicals released at synapsed open up the receptors on the post-synaptic membrane. These receptors let in specific ions according to their size and shape. On the post-synaptic membrane, you can find receptors which let in sodium ions or both sodium and calcium ions (an even more positive species). Opening these receptors leads to a huge influx of positive ions into the post-synaptic neuron and hence, a 'burst' can be initiated. The burst-‘promoting’ receptors are opened by a chemical called glutamate; stored in the pre-synaptic terminal and released into the cleft. Glutamate binds to receptors called AMPA (lets sodium ions in) and NMDA (lets both sodium and calcium ions in). The type of receptor of the post-synaptic membrane or the number of these receptors determines how easy it is for a signal to be passed on. For example, if you have a post-synaptic membrane packed with loads of NMDA receptors, the post-synaptic membrane will become positively charged more easily than if you had a few AMPA receptors. This balance is how different synapses are ‘stronger’ than others.

There are also synapses that inhibit action potential signalling, and these contain receptors called GABA receptors. A GABA receptor is very different to an AMPA or NMDA receptor as it only lets through chloride ions; negatively charged species at higher concentrations outside the neuron than in. GABA receptors are opened by the chemical GABA, stored in some pre-synaptic terminals. When GABA binds to GABA receptors, negative chloride ions flood inside the post-synaptic neuron and drive its membrane potential down. This means that incoming signals are stopped as sodium ion channels cannot open at these low voltages. Having inhibitory synapses are really important in some neuronal circuits as too much signalling can be a bad thing. For example, inhibitory synapses can be found in the spinal cord to stop your muscles constantly contracting once you have used them. So, the balance of action potential-promoting and -inhibiting synapses is vital for normal functioning.

 

With all of these receptors, chemicals can only stay bound for a short period of time; forcing them to close and terminate their action. This again is dead important for transmitting individual, isolated signals across the synapse.

Signing Off

Your synapses are the meet-point for all neuron convos; whether these be passing messages on or stopping them dead. The chemicals released from the pre-synaptic cell and the receptors on the post-synaptic cell determine the direction of signalling and how strong this signalling will be. The more a synapse is used, the stronger is becomes; leading to an increase the number of receptors on the post-synaptic membrane. Synaptic architecture creates circuits within your brain and is the basis of memory formation… but more about that in future. For now, I will leave you and your 100 trillion synapses to absorb all this information. Happy firing!