In the course of lectures “Anatomy of the Central Nervous System for Psychologists,” I already wrote about anatomical terminology and the nervous system. In this article, I decided to talk about nervous tissue, its features, types of nervous tissue, classifications of neurons, nerve fibers, types of glial cells and much more.
I would like to remind you that I write all the articles in the “Anatomy of the Central Nervous System” section specifically for psychologists, taking into account their training program. I remember from my own experience how difficult and unusual it was to study such topics during my studies. Therefore, I try to present all the material as clearly as possible.
Nervous system
Most cells in the body have a similar structure. They have a compact shape enclosed in a shell. Inside there is a nucleus and a set of organelles that perform the synthesis and metabolism of necessary substances. However, the structure and functions of the neuron are different. It is a structural unit of nervous tissue. These cells provide communication between all body systems.
The basis of the central nervous system is the brain and spinal cord. These two centers secrete gray and white matter. The differences are related to the functions performed. One part receives a signal from the stimulus and processes it, while the other is responsible for carrying out the necessary response command. Outside the main centers, the nervous tissue forms bundles of clusters (nodes or ganglia). They branch, spreading a signal-conducting network throughout the body (peripheral nervous system).
Nerve cells
To provide multiple connections, the neuron has a special structure. In addition to the body, in which the main organelles are concentrated, there are processes. Some of them are short (dendrites), usually there are several of them, the other (axon) is one, and its length in individual structures can reach 1 meter.
The structure of the nerve cell of the neuron is designed in such a way as to ensure the best interchange of information. Dendrites are highly branched (like the crown of a tree). With their endings they interact with the processes of other cells. The place where they meet is called a synapse. This is where the impulse is received and transmitted. Its direction: receptor – dendrite – cell body (soma) – axon – reacting organ or tissue.
The internal structure of a neuron is similar in composition to organelles to other structural units of tissue. It contains a nucleus and cytoplasm bounded by a membrane. Inside there are mitochondria and ribosomes, microtubules, the endoplasmic reticulum, and the Golgi apparatus.
What else?
The energy efficiency of brain cells has also been studied in relation to their morphology [35], [52–54]. Studies show that the branching of dendrites and axons is not chaotic and also saves energy [52], [54]. For example, an axon branches so that the total length of the path that passes through the AP is minimal. In this case, the energy consumption for conducting AP along the axon is minimal.
A reduction in neuron energy consumption is also achieved at a certain ratio of inhibitory and excitatory synapses [55]. This is directly related, for example, to ischemia (a pathological condition caused by impaired blood flow in the vessels) of the brain. In this pathology, the most metabolically active neurons are most likely to fail first [9], [16]. In the cortex, they are represented by inhibitory interneurons that form inhibitory synapses on many other pyramidal neurons [9], [16], [49]. As a result of the death of interneurons, the inhibition of pyramidal neurons decreases. As a consequence, the overall level of activity of the latter increases (activating synapses fire more often, APs are generated more often). This is immediately followed by an increase in their energy consumption, which under ischemic conditions can lead to the death of neurons.
When studying pathologies, attention is paid to synaptic transmission as the most energy-consuming process [19]. For example, in Parkinson's [56], Huntington's [57], and Alzheimer's diseases [58–61], there is a disruption in the functioning or transport to the synapses of mitochondria, which play a major role in the synthesis of ATP [62], [63]. In the case of Parkinson's disease, this may be due to disruption and death of highly energy-consuming neurons of the substantia nigra, which is important for the regulation of motor functions and muscle tone. In Huntington's disease, the mutant protein huntingtin disrupts the delivery mechanisms of new mitochondria to synapses, which leads to “energy starvation” of the latter, increased vulnerability of neurons and excessive activation. All this can cause further disruption of neuronal function with subsequent atrophy of the striatum and cerebral cortex. In Alzheimer's disease, mitochondrial dysfunction (in parallel with a decrease in the number of synapses) occurs due to the deposition of amyloid plaques. The effect of the latter on mitochondria leads to oxidative stress, as well as apoptosis - cell death of neurons.
Structure and types of neurons
In most cases, several thick branches (dendrites) extend from the cell soma (base). They do not have a clear boundary with the body and are covered with a common membrane. As they move away, the trunks become thinner and branch out. As a result, their thinnest parts look like pointed threads.
The special structure of the neuron (thin and long axon) implies the need to protect its fiber along its entire length. Therefore, on top it is covered with a sheath of Schwann cells that form myelin, with nodes of Ranvier between them. This structure provides additional protection, isolates passing impulses, and additionally nourishes and supports the threads.
The axon originates from a characteristic hill (mound). The process eventually also branches, but this does not occur along its entire length, but closer to the end, at the points of connection with other neurons or tissues.
Classification
Neurons are divided into types depending on the type of mediator (mediator of the conductive impulse) released at the axon terminals. This can be choline, adrenaline, etc. Depending on their location in the parts of the central nervous system, they can relate to somatic neurons or autonomic ones. There are receptive cells (afferent) and transmitting feedback signals (efferent) in response to irritation. Between them there may be interneurons responsible for the exchange of information within the central nervous system. Depending on the type of response, cells can inhibit excitation or, conversely, increase it.
According to their state of readiness, they are distinguished: “silent”, which begin to act (transmit an impulse) only in the presence of a certain type of irritation, and background, which constantly monitor (continuous generation of signals). Depending on the type of information perceived from the sensors, the structure of the neuron also changes. In this regard, they are classified into bimodal, with a relatively simple response to irritation (two interrelated types of sensation: a prick and, as a result, pain, and polymodal. This is a more complex structure - polymodal neurons (specific and ambiguous reaction).
Action potential
Action potential ( AP ) is a signal that neurons send to each other. APs can be different: fast and slow, small and large [28]. They are often organized in long sequences (like letters in words) or in short, high-frequency “packs” (Fig. 2).
Figure 2. Different types of neurons generate different signals. In the center is a longitudinal section of the mammal's brain. The boxes show different types of signals recorded by electrophysiological methods [15], [38]. a — Cortical (Cerebral cortex) pyramidal neurons can transmit both low-frequency signals (Regular firing) and short explosive, or burst, signals (Burst firing). b - Purkinje cells of the cerebellum (Cerebellum) are characterized only by burst activity at a very high frequency. c — Relay neurons of the thalamus (Thalamus) have two modes of activity: burst and tonic (Tonic firing). d — Neurons in the middle part of the leash (MHb, Medial habenula) of the epithalamus generate low-frequency tonic signals.
[14], figure adapted
The wide variety of signals is due to the huge number of combinations of different types of ion channels, synaptic contacts, as well as the morphology of neurons [28], [29]. Since neuronal signaling processes are based on ionic currents, it is expected that different APs require different energy inputs [20], [27], [30].
What is an action potential?
- Membrane and ions. The plasma membrane of a neuron maintains an uneven distribution of substances between the cell and the extracellular environment (Fig. 3b) [31–33]. Among these substances there are also small ions, of which K+ and Na+ are important for describing PD. There are few Na+ ions inside the cell, but many outside. Because of this, they constantly strive to get into the cage. On the contrary, there are a lot of K+ ions inside the cell, and they strive to leave it. The ions cannot do this on their own, because the membrane is impermeable to them. For ions to pass through the membrane, it is necessary to open special proteins—membrane ion channels.
- Ion channels. The variety of channels is enormous [14], [36], [38], [39]. Some open in response to a change in membrane potential, others - upon binding of a ligand (a neurotransmitter in a synapse, for example), others - as a result of mechanical changes in the membrane, etc. Opening a channel involves changing its structure, as a result of which ions can pass through it. Some channels allow only a certain type of ion to pass through, while others are characterized by mixed conductivity. In the generation of AP, a key role is played by channels that “sense” the membrane potential—voltage-dependent ion channels. They open in response to changes in membrane potential. Among them, we are interested in voltage-gated sodium channels (Na channels), which allow only Na+ ions to pass through, and voltage-gated potassium channels (K-channels), which allow only K+ ions to pass through.
- Ion current and PD. The basis of AP is the ion current—the movement of ions through the ion channels of the membrane [38]. Since the ions are charged, their current leads to a change in the net charge inside and outside the neuron, which immediately entails a change in the membrane potential. Generation of APs, as a rule, occurs in the initial segment of the axon—in that part that is adjacent to the neuron body [40], [14]. Many Na channels are concentrated here. If they open, a powerful current of Na+ ions will flow into the axon, and membrane depolarization will occur—a decrease in membrane potential in absolute value (Fig. 3c). Next, it is necessary to return to its original meaning - repolarization. K+ ions are responsible for this. When the K channels open (shortly before the AP maximum), K+ ions will begin to leave the cell and repolarize the membrane. Depolarization and repolarization are the two main phases of AP. In addition to them, there are several more, which, due to lack of necessity, are not considered here. A detailed description of PD generation can be found in [14], [29], [38], [41]. A brief description of PD is also available in articles on Biomolecule [15], [42].
- Initial axon segment and AP initiation. What causes Na channels to open at the axon initial segment? Again, a change in membrane potential “coming” along the dendrites of the neuron (Fig. 3a). These are postsynaptic potentials (PSPs) that arise as a result of synaptic transmission. This process is explained in more detail in the main text.
- Conducting PD. Na-channels located nearby will be indifferent to the AP in the initial segment of the axon. They too will open in response to this change in membrane potential, which will also cause AP. The latter, in turn, will cause a similar “reaction” on the next section of the axon, further and further from the neuron body, and so on. In this way, AP conduction occurs along the axon [14], [15], [38]. Eventually it will reach its presynaptic terminals (magenta arrows in Fig. 3a), where it can cause synaptic transmission.
- Energy consumption for the generation of APs is less than for the operation of synapses. How many molecules of adenosine triphosphate (ATP), the main energy “currency”, does PD cost? According to one estimate, for pyramidal neurons of the rat cerebral cortex, the energy consumption for generating 4 APs per second is about ⅕ of the total energy consumption of the neuron. If we take into account other signaling processes, in particular synaptic transmission, the share will be ⅘. For the cerebellar cortex, which is responsible for motor functions, the situation is similar: the energy consumption for generating the output signal is 15% of the total, and about half is for processing input information [25]. Thus, PD is far from the most energy-intensive process. The operation of a synapse requires many times more energy [5], [19], [25]. However, this does not mean that the PD generation process does not exhibit energy efficiency features.
Figure 3. Neuron, ion channels and action potential. a — Reconstruction of a candelabra cell in the rat cerebral cortex. The dendrites and body of the neuron are colored blue (blue spot in the center), the axon is colored red (in many types of neurons the axon is branched much more than the dendrites [8], [11], [35]). Green and crimson arrows indicate the direction of information flow: the dendrites and body of the neuron receive it, the axon sends it to other neurons. b - The membrane of a neuron, like any other cell, contains ion channels. Green circles are Na+ ions, blue circles are K+ ions. c — Change in membrane potential during the generation of an action potential (AP) by a Purkinje neuron. Green area: Na channels are open, Na+ ions enter the neuron, depolarization occurs. Blue area: K channels are open, K+ comes out, repolarization occurs. The overlap of the green and blue regions corresponds to the period when simultaneous entry of Na+ and exit of K+ occurs.
[34], [36], [37], figures adapted
AP is a relatively strong in amplitude stepwise change in membrane potential.
Analysis of different types of neurons (Fig. 4) showed that invertebrate neurons are not very energy efficient, while some vertebrate neurons are almost perfect [20]. According to the results of this study, the most energy efficient were the interneurons of the hippocampus, which is involved in the formation of memory and emotions, as well as thalamocortical relay neurons, which carry the main flow of sensory information from the thalamus to the cerebral cortex.
Figure 4. Different neurons are efficient in different ways. The figure shows a comparison of the energy consumption of different types of neurons. Energy consumption is calculated in models with both initial (real) parameter values (black columns) and optimal ones, in which, on the one hand, the neuron performs its assigned function, and on the other, it spends a minimum of energy (gray columns). The most effective of the presented ones turned out to be two types of vertebrate neurons: hippocampal interneurons (rat hippocampal interneuron, RHI) and thalamocortical neurons (mouse thalamocortical relay cell, MTCR), since for them the energy consumption in the original model is closest to the energy consumption of the optimized one. In contrast, invertebrate neurons are less efficient. Legend: SA (squid axon) - squid giant axon; CA (crab axon) - crab axon; MFS (mouse fast spiking cortical interneuron) - fast cortical interneuron of the mouse; BK (honeybee mushroom body Kenyon cell) - mushroom-shaped Kenyon cell of a bee.
[20], figure adapted
Why are they more effective? Because they have little overlap of Na- and K-currents. During the generation of APs, there is always a period of time when these currents are present simultaneously (Fig. 3c). In this case, practically no charge transfer occurs, and the change in membrane potential is minimal. But in any case, you have to “pay” for these currents, despite their “uselessness” during this period. Therefore, its duration determines how much energy resources are wasted. The shorter it is, the more efficient the energy use [20], [26], [30], [43]. The longer, the less effective. In just the two above-mentioned types of neurons, thanks to fast ion channels, this period is very short, and APs are the most effective [20].
By the way, interneurons are much more active than most other neurons in the brain. At the same time, they are extremely important for the coordinated, synchronous operation of neurons, with which they form small local networks [9], [16]. Probably, the high energy efficiency of AP interneurons is some kind of adaptation to their high activity and role in coordinating the work of other neurons [20].
Features, structure and functions of a neuron
The surface of the neuron membrane is covered with small projections (spikes) to increase the contact area. In total, they can occupy up to 40% of the cell area. The nucleus of a neuron, like that of other types of cells, carries hereditary information. Nerve cells do not divide by mitosis. If the connection between the axon and the body is broken, the process dies. However, if the soma has not been damaged, it is able to generate and grow a new axon.
The fragile structure of the neuron suggests the presence of additional “care”. Protective, supporting, secretory and trophic (nutrition) functions are provided by neuroglia. Its cells fill all the space around. To a certain extent, it helps restore broken connections, and also fights infections and generally “takes care” of neurons.
Origin of the approach
Since the mid-twentieth century, it has been known that the brain consumes a significant part of the energy resources of the whole organism: a quarter of all glucose and ⅕ of all oxygen in the case of the great ape [1–5]. This inspired William Levy and Robert Baxter from the Massachusetts Institute of Technology (USA) to conduct a theoretical analysis of the energy efficiency of information encoding in biological neural networks (Fig. 1) [6]. The study is based on the following hypothesis. Since the brain's energy consumption is high, it is beneficial for it to have neurons that work most efficiently - transmitting only useful information and expending a minimum of energy.
This assumption turned out to be true: using a simple neural network model, the authors reproduced the experimentally measured values of some parameters [6]. In particular, the optimal frequency of impulse generation they calculated varies from 6 to 43 impulses/s - almost the same as for neurons at the base of the hippocampus. They can be divided into two groups according to the pulse frequency: slow (~10 pulses/s) and fast (~40 pulses/s). Moreover, the first group significantly outnumbers the second [7]. A similar picture is observed in the cerebral cortex: there are several times more slow pyramidal neurons (~4-9 impulses/s) than fast inhibitory interneurons (>100 impulses/s) [8], [9]. Thus, apparently, the brain “prefers” to use fewer fast and energy-consuming neurons so that they do not use up all their resources [6], [9–11].
Figure 1. Two neurons are shown. In one of them, the presynaptic protein synaptophysin is colored purple. Another neuron is completely stained with green fluorescent protein. Small light specks are synaptic contacts between neurons [12]. In the inset, one “speck” is presented closer. Groups of neurons connected by synapses are called neural networks [13], [14]. For example, in the cerebral cortex, pyramidal neurons and interneurons form extensive networks. The coordinated “concert” work of these cells determines our higher cognitive and other abilities. Similar networks, only made up of different types of neurons, are distributed throughout the brain, connected in a certain way and organize the work of the entire organ.
website embryologie.uni-goettingen.de
What are interneurons?
Neurons of the central nervous system are divided into activating (forming activating synapses) and inhibitory (forming inhibitory synapses). The latter are largely represented by interneurons , or intermediate neurons. In the cerebral cortex and hippocampus, they are responsible for the formation of gamma rhythms in the brain [15], which ensure the coordinated, synchronous work of other neurons. This is extremely important for motor functions, perception of sensory information, and memory formation [9], [11].
Interneurons are distinguished by their ability to generate significantly higher frequency signals than other neurons. They also contain more mitochondria, the main organelles of energy metabolism and ATP production factories. The latter also contain a large amount of proteins cytochrome c oxidase and cytochrome c, which are key for metabolism. Thus, interneurons are extremely important and, at the same time, energy-consuming cells [8], [9], [11], [16].
The work of Levy and Baxter [6] develops the concept of “economy of impulses” by Horace Barlow from the University of California (USA), who, by the way, is a descendant of Charles Darwin [17]. According to it, during the development of the body, neurons tend to work only with the most useful information, filtering out “extra” impulses, unnecessary and redundant information. However, this concept does not provide satisfactory results, since it does not take into account the metabolic costs associated with neuronal activity [6]. Levy and Baxter's extended approach, which focuses on both factors, has been more fruitful [6], [18–20]. Both the energy expenditure of neurons and the need to encode only useful information are important factors guiding brain evolution [6], [21–24]. Therefore, in order to better understand how the brain works, it is worth considering both of these characteristics: how much useful information a neuron transmits and how much energy it spends.
Recently, this approach has found many confirmations [10], [22], [24–26]. It allowed us to take a new look at the structure of the brain at various levels of organization - from molecular biophysical [20], [26] to organ [23]. It helps to understand what the trade-offs are between the function of a neuron and its energy cost and to what extent they are expressed.
How does this approach work?
Suppose we have a model of a neuron that describes its electrophysiological properties: action potential ( AP ) and postsynaptic potentials ( PSP ) (more on these terms below). We want to understand whether it works efficiently and whether it wastes an unreasonable amount of energy. To do this, it is necessary to calculate the values of the model parameters (for example, the density of channels in the membrane, the speed of their opening and closing), at which: (a) the maximum ratio of useful information to energy consumption is achieved and at the same time (b) realistic characteristics of the transmitted signals are preserved [6 ], [19].
Search for the optimum
In fact, we are talking about an optimization problem: finding the maximum of a function and determining the parameters under which it is achieved. In our case, the function is the ratio of the amount of useful information to energy costs. The amount of useful information can be approximately calculated using Shannon's formula, widely used in information theory [6], [18], [19]. There are two methods for calculating energy costs, and both give plausible results [10], [27]. One of them - the “ion counting method” - is based on counting the number of Na+ ions that entered the neuron during a particular signaling event (AP or PSP, see sidebar “What is an action potential”) with subsequent conversion to the number of adenosine triphosphate (ATP) molecules ), the main energy “currency” of cells [10]. The second is based on the description of ionic currents through the membrane according to the laws of electronics and allows one to calculate the power of the equivalent electrical circuit of a neuron, which is then converted into ATP costs [17].
These “optimal” parameter values must then be compared with those measured experimentally to determine how different they are. The overall picture of the differences will indicate the degree of optimization of a given neuron as a whole: how real, experimentally measured, parameter values coincide with the calculated ones. The less pronounced the differences, the closer the neuron is to the optimum and the more energetically it works optimally. On the other hand, a comparison of specific parameters will show in what specific quality this neuron is close to the “ideal”.
Next, in the context of the energetic efficiency of neurons, two processes on which the encoding and transmission of information in the brain are based are considered. This is a nerve impulse, or action potential, thanks to which information can be sent to the “addressee” over a certain distance (from micrometers to one and a half meters) and synaptic transmission, which underlies the actual transmission of a signal from one neuron to another.
Cell membrane
This element provides a barrier function, separating the internal environment from the neuroglia located outside. The thinnest film consists of two layers of protein molecules and phospholipids located between them. The structure of the neuron membrane suggests the presence in its structure of specific receptors responsible for recognizing stimuli. They have selective sensitivity and, if necessary, “turn on” in the presence of a counterparty. The connection between the internal and external environments occurs through tubules that allow calcium or potassium ions to pass through. At the same time, they open or close under the influence of protein receptors.
Thanks to the membrane, the cell has its potential. When it is transmitted along the chain, excitable tissue is innervated. Contact between the membranes of neighboring neurons occurs at synapses. Maintaining a constant internal environment is an important component of the life of any cell. And the membrane subtly regulates the concentration of molecules and charged ions in the cytoplasm. At the same time, they are transported in the required quantities for metabolic reactions to occur at an optimal level.
