Your question is an excellent one and sits at the core of modern neuroscience. Neuroscientists attempt to answer your question by cataloging: the shapes of neurons, their electrical properties, what molecules they express, and what other cells they connect to. A talented neuroscientist named Jason is currently working on a post discussing these attempts. I'd like to add another property to this list: neurotransmission, or how individual cells communicate with one another. Neurons can send signals to one another, much like how we can send signals (our voices) over phone-lines to our friends, who then hear our voices and respond. Neuroscientists are very interested in understanding the fundamentals of this neural communication and the different forms of signals. Now, let’s break this broad field into its primary parts.
Chemical vs. Electrical Synapses
Neurons communicate at specific sites, which we call synapses. Synapses come in variety of flavors, with two main types being chemical and electrical synapses.
Neurons with electrical synapses physically touch one another at their synapses and have specialized pores that allow electrically charged ions (mainly potassium, sodium, calcium, and chloride ions) to flow between them. This type of synapse allows for (almost) instantaneous communication between all of the connected neurons, which is crucial for various brain processes. For instance, a region of our central nervous system called the brainstem takes advantage of electrical synapses to synchronize many cells and produce the rhythms that drive breathing (see Rekling et al. 2000).
However, communication does not only occur through electrical synapses. In fact chemical synapses are the primary forms of connections. These synapses make use of small molecules called neurotransmitters. Unlike electrical synapses, chemical synapses do not physically contact but send these neurotransmitters across a small space between the neurons. There are many types of neurotransmitters, but specific neurons might only release one or a few of these. Further, the receiving neurons have selective molecules on their surfaces that respond only to a specific (or a few specific) neurotransmitters. In other words, neurons that speak a certain “language” are heard only by the downstream cells that understand that language.
So, we know that two broad categories of synapses - electrical and chemical - exist, and it appears that neuroscientists can, to some extent, classify distinct groups of neurons based on the existence of chemical vs. electrical synapses (some cells express both, while others only have chemical synapses). Now, let’s dive into chemical synapses, which come in a wide range of subtypes. For the purposes of keeping this response reasonably sized, we’ll focus only on a few major neurotransmitters.
Glutamate is a major excitatory neurotransmitter, meaning it increases the activity of the neuron that it binds to (the postsynaptic neuron) and thus increases the probability that this neuron will then ‘fire’ and send its own signal. A well-known example of glutamate-expressing neurons (which we call glutamatergic) are the neurons involved in the flight-or-fight response. For instance, some glutamatergic synapses in the hypothalamus are involved in raising blood pressure and heart rate (see Martin & Haywood 1992). However, it is important to note that neurons expressing glutamate are not all functionally or anatomically similar. So, while distinguishing glutamatergic neurons from other neurons is a step forward in classifying distinct neuronal subtypes, there are still further layers of complexity that pose a challenge when labeling neuron groups.
Neurons that use GABA (gamma-amynobutyric acid) as their primary neurotransmitter are deemed inhibitory, meaning they act oppositely to excitatory glutamateric neurons: instead of increasing the activity of the postsynaptic neuron, they decrease the activity. GABA-expressing or “GABAergic” neurons are widely distributed throughout the brain. One of their major roles is to synchronize the activity of large populations of cells. For instance, GABAergic neurons in a region called the thalamus can synchronize other regions of the brain and produce widespread periodic activity (Ulrich & Huguenard 1997). Often these synchronizations are very useful (for example, when we sleep distant areas of our brains become synchronized), but other times large synchronization is related to damage and chaos, as in seizures. Distinguishing excitatory (glutamatergic) from inhibitory (GABAergic) neurons is one crucial step towards identifying different neuron types and helps researchers better understand the functional roles of networks that they study.
Acetylcholine – ACh – is expressed in a variety of neurons, notably in neurons found in the spinal cord that contact muscles. In the motor system, ACh leaves the spinal neuron and binds to receptors on the muscle fiber, which excites the fiber and causes contraction. But in the brain, ACh can be both excitatory and inhibitory. Rather than acting directly as a neurotransmitter, here we can say that ACh acts more as a neuromodulator – a molecule that modulates the properties of the neurons it binds to. This poses an interesting question: how can a molecule be both excitatory and inhibitory? This is a difficult question to answer (one that scientists are still investigating), but we know that different modulatory effects are due to the specific receptors that the receiving neurons express. In other words, whether ACh is excitatory or inhibitory is dependent on the receptors that it binds to. You might have heard of other common neuromodulators such as dopamine, which is famous for its role in reward-motivated behavior.
What about Glia?
Before I wrap up this discussion, I want to acknowledge the glia cells in our brains. Glia are cells that are not neurons. We have many more glia than we have neurons, and they seem to play an extremely important role in keeping the rest of our brain healthy. There is also significant evidence that glia - specifically a type of glia called an astrocyte - regulate, recycle, and produce the neurotransmitters that our neurons use to communicate with one another at chemical synapses (see Hertz et al 1999). And if things weren’t complicated enough, it turns out that there are multiple types of glia cells. Another example is microglia – these are the defense cells of our brains that respond to damage and disease, and they can produce a vast array of repairs including tissue reconstruction and activation of other defense cells against infection.
While this list is certainly far from comprehensive, I hope it has given you a more specific look into certain subtypes of neurons and their functional properties. I also hope it has helped you understand why your question is such an important one for neuroscientists, as we are still in the process of trying to answer it in a variety of ways. It seems every time a new discovery is made a new mystery appears, which is definitely part of the fun of science…there’s always something new to discover.