2.1 Neural Communication

Communication between neurons happens chemically, at synapses

The chemical signaling that occurs between neurons happens primarily at chemical synapses (Figure 2.4), specialized communication structures where a broadcasting neuron and a receiving neuron draw very close to one another, separated only by a small pocket of extracellular space called a synaptic cleft. One neuron releases transmitter into the synaptic cleft—we call this the pre-synaptic neuron and say that it contains the pre-synaptic terminal. The presynaptic terminal stores neurotransmitter in small membrane-bound bubbles called vesicles (Step 1 in Figure 2.4). In response to an action potential within the neuron, these vesicles fuse with the pre-synaptic membrane and dump their neurotransmitter into the synaptic cleft (Step 2 in Figure 2.4). The other neuron is studded with specialized receptors that recognize the transmitter and respond to it—we call this the post-synaptic neuron and say that it contains the post-synaptic terminal. There are many different neurotransmitters and many different transmitter receptors. Despite this complexity, each chemical message received is translated by receptors into one of just three responses in the post-synaptic neuron (Step 3 in Figure 2.4):

Figure 2.4 Chemical communication by neurons

• An Excitatory Post-Synaptic Potential (EPSP), a brief electrical change in the post-synaptic neuron that excites the neuron, pushing it towards firing an action potential.
• An Inhibitory Post-Synaptic Potential (IPSP), a brief electrical change in the post-synaptic neuron that inhibits the neuron, pushing it away from firing an action potential.
• Neuromodulation, a change in intracellular signaling in the post-synaptic neuron that modulates that neuron, changing its patterns of growth, connectivity, or signaling.

Almost as soon as it is released, neurotransmitter is broken down and recycled, inactivating the receptors on the post-synaptic membrane (Step 4 in Figure 2.4). This ensures your synapses don’t clog up with accumulated neurotransmitter over time. More importantly, it tunes neural communication to the here and now, making their messages to one another extremely transient (short-lived). Each EPSP and IPSP lasts only a few milliseconds (bottom of Figure 2.4). The one exception to this rule is modulation, which is usually short-lived, but which can also become long-lasting; more details on modulation are in Chapter 3 Basic Neurochemistry.

The chemical communication that occurs between neurons is a specialization of systems that appeared very early in the history of life. Even bacteria can secrete chemicals and have receptors that stick through their membranes to detect and respond to chemicals in their environment. Many of the neurotransmitters and transmitter receptors used in your nervous system have long evolutionary histories, so it is not uncommon to find similar chemicals and proteins both in other forms of life and in other parts of your body. For example, histamine is an important neurotransmitter, but is also produced in white blood cells as part of an immune response to injury. This is part of the reason why substances in the natural world can influence your nervous system (caffeine!) and why drugs developed to treat brain disorders often have unwanted side effects in other parts of the body.

Although chemical communication between neurons has ancient roots, it has become highly specialized in neurons. One key specialization is that chemical communication is precisely targeted. Neurons release neurotransmitter almost exclusively at synapses. The tiny volume of the synaptic cleft ensures the post-synaptic neuron will get the message, and that other neurons (for the most part) will not. The pre-synaptic terminal also has specialized protein machinery to maintain a steady supply of neurotransmitter for release, and the post-synaptic terminal is loaded with receptors as well as other proteins that anchor the receptors and help fine-tune their responses to synaptic signals.

Although most communication between neurons occurs via chemical synapses, neurons can also signal to each other through electrical synapses (Figure 2.5); At an electrical synapse, neurons express a specialized protein, called connexon, which forms a protein bridge called a gap junction between the neurons. This enables electrical signals to pass directly from one neuron to another. In addition, small molecules can pass through an electrical synapse, so they actually allow for both electrical and chemical communication.

Figure 2.5 Electrical synapses Image credit: Tsukamoto Y and Omi N (2017) Classification of Mouse Retinal Bipolar Cells: Type-Specific Connectivity with Special Reference to Rod-Driven AII Amacrine Pathways. Front. Neuroanat. 11:92. doi: 10.3389/fnana.2017.00092. CC BY 4.0.

If you find communication between neurons fascinating, you’re not alone and you’re also in luck. When you get to Chapter 3 Basic Neurochemistry, you’ll read more about chemical communication between neurons.

Information spreads within a neuron electrically

Neurons are specialized not only for communicating with each other, but also for generating internal electrical signals (Figure 2.6). Like almost all cells, neurons maintain an overall negative charge called a resting potential. In addition, neurons are electrically excitable, generating action potentials that sweep through a neuron at speeds up to 60 meters per second (134 miles per hour; Todnem et al., 1989). Each action potential is translated back into chemical messages released to partner neurons.

Figure 2.6 Action potential spread and neurotransmitter release

How does a neuron decide when to “fire” an action potential? Based, in part, on the constant barrage of chemical messages it is receiving on the post-synaptic side of its synaptic contacts. The EPSPs and IPSPs produced by these messages push a neuron above or below its threshold for generating an action potential (Step 1 in Figure 2.6). When the balance of excitation and inhibition being received is below a neuron’s threshold, the neuron does not fire an action potential or release transmitter to its partner neurons. When the balance of excitation and inhibition rises above a neuron’s threshold, it fires an action potential (Step 2 in Figure 2.6). The action potential spreads from the cell body along the length of the axon and all of its branches (Step 3 in Figure 2.6). As it spreads, the action potential is translated back into chemical messages, triggering the release of neurotransmitter from the pre-synaptic side of all the neuron’s synaptic contacts (Step 4 in Figure 2.6). A neuron firing an action potential is said to be activated or excited, with each action potential producing a burst of chemical signals to its synaptic partners.

The more excitation a neuron receives, the more frequently it fires action potentials. But this doesn’t make the action potential itself taller, stronger, or faster. Action potentials are ‘all-or-nothing’—each action potential a neuron generates is basically just like every other. There can be, however, considerable diversity between neurons. For example, some neurons fire action potentials that spread very quickly; others fire action potentials that spread more slowly. In addition, neurons are highly dynamic. Experience, disease, and maturation can change a neuron’s threshold, which synaptic partnerships it maintains, and more. For example, modulatory signaling in your nervous system is constantly fine-tuning action potential thresholds, lowering them to produce more activity during times of concentration and raising them to produce less activity during rest and sleep (more on this in Chapter 15 Biological Rhythms and Sleep).

Excitation and inhibition from partner neurons are not the only factors that determine when a neuron fires an action potential. Some neurons fire action potentials in response to changes in the outside world. We call these sensory neurons. In addition, most neurons in your nervous system generate action potentials spontaneously, meaning that they generate action potentials from time to time even without excitatory messages from partner neurons. For example, motor neurons, the neuron which release transmitter onto muscles, are often spontaneously active. This regular activity in your motor neurons maintains muscle tone (see Chapter 10 Motor Control). In spontaneously active neurons, EPSPs and IPSPs from partner neurons serve to speed up (when excited) or slow down (when inhibited) the rate at which action potentials are fired. In Figure 2.7 you can see an example of a sensory neuron (left) responding to the outside world and a spontaneously-active motor neuron (right) that changes its rate of firing to control muscle tension.

Figure 2.7 Internal and external triggers for action potentials

The electrical signaling system in neurons is relatively new in the history of life, emerging at the dawn of the Animal kingdom at least 500 million years ago (though with important precursors in other life forms; Anctil, 2015). Electrical signaling enables neurons to coordinate information throughout your body with speed and precision, something that would be difficult to do with chemical communication alone. For example, you have sensory neurons in your toe (Figure 2.8). The axons of these neurons ascend in your sciatic nerve to the base of your spine (depending on how tall you are, that can be a distance of up to 1 meter!). Pinch your big toe and you will trigger action potentials in your toe sensory neurons that spread to the spine within a couple of milliseconds, releasing transmitter onto partner neurons in the spine. Some of these partner neurons will send signals back down to the muscles of your leg and foot to cause muscle contractions to jerk your foot away from the pain. Other neurons will generate action potentials that spread rapidly to the brain, hopefully triggering you to question your life choices:

Figure 2.8 Simple reflex circuit

Why would you pinch your big toe? Just because your neuroscience textbook told you to? These circuits, showing neural circuit from sensory neuron to spinal interneuron to motor neuron, are diagrammed at the top of Figure 2.8.

Neurons don’t just transfer information; they also process information. Each neuron synthesizes the excitation and inhibition received from thousands of synaptic partners, instantly tallying up these different influences to help determine when an action potential will be generated. In addition, the threshold for an action potential means that neurons filter information. Inputs that push a neuron above threshold produce action potentials, which then cause neurotransmitter release to partner neurons. Inputs that do not reach threshold are essentially ‘ignored’ or filtered out. For example, recall again the toe-pinching experiment shown in Figure 2.8. The interneuron in that circuit filters out gentle stimuli, ensuring only painful stimuli produce a withdrawal. If your toe is only lightly touched (bottom left), there won’t be very much sensory neuron activity, so the interneuron will receive some excitation but not quite enough to get to threshold. In that case, the interneuron does not fire an action potential, and the motor neuron never gets the message: the light touch is ignored. A strong pinch, though (Ow!), produces enough sensory activity to drive the interneuron to threshold (bottom right), and it passes along the message to the motor neuron, producing a behavior to get away from the painful stimulus. Thresholds give neural circuits the ability to ignore some events and respond to others, a key ability for using the body’s energy wisely.