Neurons communicate through coordinated electrical and chemical signalling. Within an individual neuron, information is represented partly through changes in membrane voltage and the generation of action potentials. Between many neurons, information is transmitted at specialised junctions called synapses, where the activity of one cell influences another. The most common form is chemical synaptic transmission, in which an action potential reaches a presynaptic terminal, triggers calcium entry and causes neurotransmitter release.
The neurotransmitter crosses the microscopic synaptic cleft and binds receptors on the postsynaptic membrane. Receptor activation changes ion flow or intracellular signalling and can either increase or decrease the probability that the postsynaptic neuron will generate an action potential. Communication is therefore not a single event but a sequence involving membrane excitability, axonal conduction, calcium signalling, vesicle fusion, receptor activation and postsynaptic integration.
The process begins when synaptic inputs alter the membrane potential of a neuron. Dendrites and the cell body may receive many excitatory and inhibitory inputs at approximately the same time. These changes spread through the membrane and are integrated, particularly near the axon initial segment. Excitatory postsynaptic potentials generally depolarise the membrane and make action potential generation more likely, while inhibitory postsynaptic potentials generally make firing less likely. Individual inputs are usually insufficient to determine behaviour by themselves.
Temporal summation occurs when repeated inputs arrive close together in time, while spatial summation occurs when inputs from different locations act together. The resulting membrane state depends on the strength, timing, location and properties of thousands of inputs in some neurons. This integration is one of the fundamental mechanisms by which neural circuits transform information.
When an action potential reaches the presynaptic terminal, depolarisation activates voltage gated calcium channels. Calcium ions enter the terminal down their electrochemical gradient and interact with specialised proteins associated with synaptic vesicles. This initiates membrane fusion and exocytosis, releasing neurotransmitter into the synaptic cleft. The transmitter then diffuses across the cleft, which is extremely narrow, and binds to receptors on the postsynaptic membrane.
The speed of this process can be very high, although the exact timing depends on the synapse and receptor type. Neurotransmitter molecules are subsequently removed through reuptake into cells, enzymatic degradation or diffusion away from the synaptic cleft. Rapid clearance is important because persistent transmitter action would interfere with precise temporal signalling.
Postsynaptic receptors determine much of the effect of a neurotransmitter. Ionotropic receptors are ligand gated ion channels that directly change ionic conductance and generally produce relatively rapid effects. Metabotropic receptors are commonly G protein coupled receptors that influence intracellular signalling pathways and ion channels indirectly, producing slower but potentially longer lasting and more modulatory effects. The same neurotransmitter can therefore produce different effects in different locations because receptor types and intracellular machinery differ.
Glutamate commonly mediates excitatory transmission in the central nervous system, while gamma aminobutyric acid is a major inhibitory transmitter. Acetylcholine, dopamine, serotonin and noradrenaline can produce diverse effects depending on receptor subtype and circuit context. It is therefore inaccurate to classify neurotransmitters permanently as either excitatory or inhibitory without specifying the receptor and cellular context.
Electrical synapses provide another communication mechanism. They use gap junctions that directly connect the cytoplasm of adjacent cells, allowing ions and small molecules to pass between them. Electrical synapses are extremely rapid and can synchronise the activity of groups of neurons. They occur in several nervous system circuits where coordinated timing is advantageous. Chemical synapses are more common for flexible information processing because they permit amplification, inhibition, modulation, plasticity and one way transmission.
Some synapses can change their strength according to recent activity, providing a cellular basis for forms of neural plasticity. Long term potentiation and long term depression are examples of activity dependent changes in synaptic efficacy that have been extensively studied in relation to learning and memory.
Neuronal communication is also shaped by the architecture of neural networks. A neuron can receive signals from many other neurons and project to numerous targets, creating highly interconnected circuits. Convergent circuits bring information from many sources into one neuron, whereas divergent circuits distribute information from one source to many targets. Recurrent circuits provide feedback and can sustain or regulate activity. Inhibitory interneurons can constrain excitation and prevent uncontrolled activity. Neuromodulatory systems can alter the responsiveness of large populations of neurons rather than simply transmitting a point to point message. Neural computation therefore depends not only on individual synapses but also on connectivity, timing, network feedback, cellular properties and the chemical environment.
Communication between neurons is remarkably adaptable. Synaptic strength can change through alterations in neurotransmitter release, receptor number, receptor sensitivity, ion channel activity and intracellular signalling. Experience can produce long lasting changes in connectivity and circuit function. Developmental processes establish many initial connections, after which activity and experience refine networks. Neuromodulators such as dopamine can influence learning, motivation and movement by changing how circuits respond to other signals. Hormones and immune mediators can also affect neural communication. This plasticity allows the nervous system to learn and adapt but also means that abnormal changes can contribute to disease. Epileptic activity, for example, can involve excessive synchronisation and excitation, while degeneration of particular signalling pathways contributes to several neurological disorders.
The overall process can therefore be summarised conceptually as reception, integration, electrical conduction, synaptic transmission and further integration, although real neural systems contain many variations. Neurons do not send thoughts as simple packets along wires. Information is encoded through patterns of activity, timing, population activity, synaptic strengths and network dynamics. Signals can be amplified, inhibited, transformed or combined at successive synapses.
The direction of chemical synaptic communication is usually from presynaptic cell to postsynaptic cell, but specialised feedback mechanisms can alter presynaptic activity. Communication is consequently both rapid and highly regulated. Understanding these mechanisms explains how sensory information can be transformed into perception, how motor commands can be coordinated, and how complex cognitive functions can emerge from interactions among enormous numbers of communicating cells.
