Synapse | How Do Your Brain Cells Talk to Each Other?

A synapse is a highly specialized structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. The fundamental role of the synapse is to transfer information, and it is the primary site of communication within the nervous system. Structurally, a typical chemical synapse is composed of three main parts. First is the presynaptic terminal, a specialized area within the axon of the presynaptic neuron that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles. Second is the synaptic cleft, a microscopic gap between the presynaptic and postsynaptic neurons, typically measuring about 20-40 nanometers wide. This cleft is not empty space; it is filled with a matrix of extracellular proteins that help anchor the neurons in place. Third is the postsynaptic terminal, which is the surface of the dendrite or cell body of the postsynaptic neuron. This surface contains specialized protein molecules called receptors. When neurotransmitters are released from the presynaptic terminal, they travel across the synaptic cleft and bind to these receptors, initiating a response in the postsynaptic neuron. This intricate structure ensures that signals are transmitted in a precise and controlled manner from one neuron to the next, forming the basis of all neural circuits.

Synaptic transmission is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and activate the receptors on the dendrites of another neuron. This process begins when an electrical signal, known as an action potential, travels down the axon of the presynaptic neuron and reaches the axon terminal. The arrival of the action potential triggers the opening of voltage-gated calcium channels, causing calcium ions to flow into the terminal. This influx of calcium causes synaptic vesicles to fuse with the presynaptic membrane and release their neurotransmitter contents into the synaptic cleft, a process called exocytosis. The neurotransmitter molecules diffuse across the cleft and bind to specific receptors on the postsynaptic membrane. This binding opens or closes ion channels, leading to a change in the membrane potential of the postsynaptic neuron. If the change is depolarizing (making it more likely to fire an action potential), it is called an excitatory postsynaptic potential (EPSP). If it is hyperpolarizing (making it less likely to fire), it is an inhibitory postsynaptic potential (IPSP). The summation of these potentials determines whether the postsynaptic neuron will generate its own action potential, thus continuing the signal.

Memories are encoded and stored in the brain through a process known as synaptic plasticity, which is the ability of synapses to strengthen or weaken over time in response to increases or decreases in their activity. The key mechanism for this is Long-Term Potentiation (LTP), a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. When a synapse is frequently used, it becomes stronger. This involves molecular changes, such as an increase in the number of neurotransmitter receptors on the postsynaptic membrane and an increase in the amount of neurotransmitter released from the presynaptic neuron. These structural and functional changes make the postsynaptic neuron more responsive to the presynaptic neuron, effectively solidifying the connection. This strengthened pathway forms the physical basis of a memory trace, or "engram."

The vast majority of synapses in the human brain are chemical synapses, which use chemical messengers (neurotransmitters) to transmit signals. They are characterized by the synaptic cleft that separates neurons. This structure ensures unidirectional communication but introduces a slight delay in signal transmission. The key advantage of chemical synapses is their plasticity; their strength can be modified, which is crucial for learning and memory. In contrast, electrical synapses are less common. Here, the membranes of two neurons are directly connected by channels called gap junctions. These channels allow ions to flow directly from one cell to another, resulting in instantaneous signal transmission. This communication is typically bidirectional and allows for the synchronized firing of a group of neurons. Electrical synapses are found in neural circuits that require very fast, reliable signaling, such as defensive reflexes.

Many psychiatric medications function by directly targeting and modulating synaptic transmission. Their primary goal is to correct imbalances in neurotransmitter systems that are thought to underlie mental health conditions like depression and anxiety. For example, a widely prescribed class of antidepressants called Selective Serotonin Reuptake Inhibitors (SSRIs) works specifically at serotonin synapses. After serotonin is released into the synaptic cleft, it is normally taken back up into the presynaptic neuron by a transporter protein in a process called reuptake. SSRIs block this transporter. By inhibiting reuptake, SSRIs increase the concentration of serotonin in the synaptic cleft, allowing it to bind to postsynaptic receptors for a longer period. This enhances serotonergic signaling between neurons. The therapeutic effects are not immediate, as the brain adapts to this change over weeks by altering receptor density and gene expression, ultimately leading to a regulation of mood and emotion.