Synapses are the connections that exist between one neuron and another, so we can think of them as the communication channel between neurons.
Gap Junctions
Electrical based
These are also called Gap Junctions
These are more direct connections between neurons, allowing excitation ions to pass through quite directly (this is the difference compared to chemically based ones). It’s a circuit more similar to an electronic one because it’s faster.
Another characteristic of these kinds of synapses is that they are two-way channels.
They are usually necessary for fast processes, such as when we want neurons to fire together, like in arc reflexes.
Electron-myscroscopy has a definition of 10nm, so it’s quite a challenge to see these gap Junctions of about 3.5nm, between each other..
We have almost instantaneous spike transmission, between the neurons (almost synchronized activity). We can interpret this as if it is passive propagation.
Speed of transmission
We can observe that most of the action potentials are transmitted to the other, so they are heavily paired.
Neurotransmitter based Synapses
What is Neurotransmitter?
They have four key properties.
- They are stored in synaptic vesicles at the presynaptic terminal
- Released in response to calcium influx during action potentials
- Bind to specific receptors on the target cell
- Are rapidly removed from the synaptic cleft (either by reuptake or enzymatic breakdown)
Examples are glutamate, GABA.
E.g. Alcohol and Cocaine are not neurotransmitters as there are no bindings to receptors, but they are called neuromodulators.
Neuropeptide transmitters
Recycling of Neurotransmitters
It takes about 10-20 seconds to recycle the neurotransmitter, so it’s quite a slow process. The whole process takes about one minute
There are many diseases that interfer with this process (for example tetratoxin, which blocks the release of neurotransmitters). They did an experiment with HRP to prove it (so you can see the recicling part).
Steps of a Synapse
We open Calcium channels at the pre-synaptic neuron, and then we have the vesicles that contain the neurotransmitter.
This leads to vesicle fusion with the membrane and the release of the neurotransmitter in the synaptic cleft.
Sodium is already used for depolarization (more granular). While Calcium is lower inside the cell, so it is a clear switch, another degree of freedom that is used.
Chemical-Based
These are slower gates, the classic ones, which we then call neurotransmitters. When there is an action potential, vesicles are released into the intra-cellular space. On the other neuron, there are receptors that pick up these neurotransmitters and activate accordingly.
They are also quite slow diffusion takes about a couple of ms to reach the other side.
The interesting thing about this method is that the receptor can change gates to determine how much it cares about this new information. (So, if it cares about that signal, it can increase the number of gates; otherwise, it can decrease them—at least, that’s the theory.)
When the neuro-trasmittor binds with the post-synaptic neuron, it triggers a release of ions in the other cell that change the membrane conductivity, and thus the voltage (see Firing-rate based Network models).
The cerebral cortex is one of the most important parts of the brain. It consists of 6 uniform layers of neurons that follow a similar pattern.
Layers 1 and 4 receive input from higher cortical areas, layer 4 from sub-cortical areas, and layer 6 from internal structures like the thalamus.
Discovery of Chemical Synapses
Experiment done by Loewi in 1921, where he took two frog hearts and stimulated the first one, then put the liquid in the second one, and it started to beat. This was the first proof of the existence of chemical synapses.
Correlations with Action Potential Timing
Between two communicating neurons, there is a fairly evident correlation that implies an increase in the strength of the connection (synaptic strength) with the timing of the spikes.
These are called Long-Term Depression and Long-Term Potentiation.
EPSP stands for Excitatory Post-Synaptic Potentiation. In the image, we see that if the second neuron activates after the first neuron has activated, the signal tends to strengthen; otherwise, it weakens.
The weakening makes sense because it’s like I’m giving the signal back to you (even if not necessarily connected), or the other neuron is just tired, lol. We will better explain these phenomena in the following section.
Long-Term Potentiation and Depression
Long-term potentiation (LTP) and long-term depression (LTD) are key neurophysiological mechanisms that underlie synaptic plasticity, which is the brain’s ability to strengthen or weaken synaptic connections over time. They’re central to learning, memory formation, and neural development. Here’s a breakdown of both:
Definition:
LTP is a long-lasting increase in synaptic strength that occurs after a high-frequency stimulation of a synapse.
Mechanism (canonical example: hippocampus):
- Glutamate Release: A presynaptic neuron fires rapidly, releasing glutamate.
- Activation of Receptors:
- Glutamate binds to AMPA receptors → Na⁺ influx → depolarization.
- If depolarization is sufficient, NMDA receptors (normally blocked by Mg²⁺) open → Ca²⁺ enters.
- Calcium Influx:
- High levels of Ca²⁺ activate protein kinases (like CaMKII and PKC).
- Synaptic Strengthening:
- More AMPA receptors are inserted into the postsynaptic membrane.
- AMPA receptors can also become more conductive.
- Over time, even structural changes occur — like dendritic spine growth.
Result: The synapse becomes more sensitive — a later stimulus evokes a stronger response. Timescale: Minutes to hours (early LTP), days to weeks or longer (late LTP, which requires gene transcription and protein synthesis).
Definition:
LTD is a long-lasting decrease in synaptic strength, often induced by low-frequency stimulation.
Mechanism (again, simplified for hippocampus/cerebellum):
- Low-frequency stimulation leads to modest, prolonged calcium influx via NMDA receptors.
- Different signaling pathways are triggered (e.g., phosphatases like PP1 and calcineurin rather than kinases).
- Internalization of AMPA receptors from the postsynaptic membrane.
- Weakened synapse: The synapse becomes less responsive to glutamate release.
Variations:
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In the cerebellum, LTD involves metabotropic glutamate receptors (mGluRs) and is critical for motor learning.
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Different brain regions and synapse types have different LTD mechanisms.
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They’re the leading candidates for cellular mechanisms of learning and memory, see Memory in Human Brain.
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Balance between LTP and LTD ensures that neural circuits adapt without becoming overexcitable or dormant.
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Dysregulation is implicated in disorders like Alzheimer’s disease, epilepsy, and autism.
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LTP: Induced via high-frequency stimulation (e.g., 100 Hz for 1 second).
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LTD: Induced via low-frequency stimulation (e.g., 1 Hz for 15 minutes).
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Both are typically studied in hippocampal slices from rodents.
| Feature | LTP | LTD |
|---|---|---|
| Ca²⁺ level | High | Moderate / sustained |
| Enzymes activated | Kinases (e.g., CaMKII, PKC) | Phosphatases (e.g., PP1, calcineurin) |
| Receptor changes | AMPA insertion/enhancement | AMPA internalization |
| Result | Stronger synaptic response | Weaker synaptic response |