Neuronal Connections: Understanding Synapses in the Human Brain

How Many Synaptic Connections Are There in the Human Brain?

Neuroscientists have long wanted to understand how neurons find each other and make connections. The key is the gap between two cells, called a synapse.

Each neuron can make up to thousands of synaptic connections, with other neurons nearby or in other parts of the brain. Each connection is electrical and chemical, mediated by molecules like neurotransmitters.


One way we remember things and process information in our brains is through a relay race that involves branches of neurons, much like electrical wire. Each neuron has an output ‘wire’ (an axon) that connects to an input ‘wire’ (a dendrite) of another neuron at a junction called a synapse. Signals travel across the synapse as chemical signals, known as neurotransmitters, to inform the receiving neuron whether or not to convey an electrical signal to other neurons.

When an action potential reaches the end of a neuron’s axon, it triggers the neuron to release a neurotransmitter from special pouches clustered near its membrane called synaptic vesicles. This neurotransmitter then diffuses across the synapse and binds to receptors on the receiving neuron. Neurons can also send messages back to pre-synaptic cells, telling them to change how often or how much neurotransmitter is released at the synapse. This bidirectional communication is known as synapse plasticity.


The dendrites of neurons receive electrical signals from other neurons and carry them to the cell body. If the input is strong enough, it can cause the neuron to fire an action potential. This process is called synaptic transmission. Larger synapses have more surface area and vesicles of neurotransmitters, so they are more likely to activate their surrounding neurons. Smaller synapses have less surface area and fewer vesicles.

While working on a 3D reconstruction of the hippocampus, researchers at Salk made a critical discovery. They noticed that in some cases, a single axon from one neuron formed two synapses reaching out to the dendrites of another neuron. This was a surprise, since scientists had previously assumed that all synapses are similar in size.

The researchers also analyzed the electrical properties of dendrites in human and rodent brain tissue. They found that human dendrites can carry signals further from the cell body than rodent dendrites. This may explain why the human brain has such a remarkable computing capacity.

Pre-synaptic terminals

Neurons transmit information through chemical synapses that are key to brain function. At these connections, an output “wire” (an axon) from one neuron meets with an input “wire” (a dendrite) of another neuron. A signal then travels across the synapse as neurotransmitter molecules. Then, the neurotransmitters are either reabsorbed by pre-synaptic neurons or cleared from the synapse by glial cells through enzymatic degradation.

This process, known as synapse transmission, is a result of electrochemical excitation waves called action potentials that travel along the axon of the presynaptic neuron. When an action potential reaches the synapse, it causes channels to open that are permeable to calcium ions. This depolarization triggers a sequence of events that includes the docking and fusion of synaptic vesicles.

The vesicles release their contents into the synaptic cleft, and the neurotransmitter molecules bind to receptors on the postsynaptic neuron. This binding leads to activation of the postsynaptic cell. Then, the neurotransmitters either are reabsorbed by pre-synaptic cells or are cleared from the synapse by specific transporters in a process called reuptake.

Post-synaptic terminals

Using advanced microscopy, scientists have been able to reconstruct the shapes, volumes and surface areas of synapses on the nano-molecular level. They have also determined how long the proteins that make up the PSDs stay in place, which is a measure of their efficacy (synaptic transmission).

When an electrical signal reaches the terminal buttons at the end of an axon beneath its myelin sheath, it causes the membranes of vesicles to change shape and fuse with the postsynaptic cell’s membrane, dumping their neurotransmitter contents into the cleft between them. The neurotransmitter diffuses across the cleft and binds to chemical receptor molecules located on the membrane of the postsynaptic cell.

These receptors then open ion channels that carry current to the postsynaptic cell and transmit the signal. At the smallest synapses, this process can take milliseconds, and is unidirectional. At the largest, it can take only a few hundred signaling events over 20 minutes to change synaptic strength/ability.

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