Chapter 10 Chapter 8 Neurons

"It is impossible for the function of the brain to be completely independent of the function of its basic unit, the nerve cell." —Idan Segev Since the "amazing hypothesis" emphasizes that "you" are the embodiment of the behavior of a large number of neurons, you should have a rough idea of ​​a neuron and what it does.Although there are many types of neurons, most of them seem to be built according to the same blueprint. ①A typical vertebrate neuron has a great deal of influence on its soma, branches—its dendrites (see Fig. 28). (shown)—stimulation of electrical impulses on the brain has three modes of response: some inputs excite it, some inhibit it, and others can modulate its behavior.When a neuron becomes quite excited, it sends a spike-shaped electrical impulse down its output cable, the axon, which also typically has many branches.The electrical signal travels along the various branches and small branches to the axon that connects with other neurons, and it also affects the behavior of other neurons.

This is the main job of neurons.It receives information from many, many other neurons, usually in the form of electrical impulses.In effect, it does a complex dynamic summation of these inputs, and then transmits the processed information in the form of a stream of electrical impulses along its axons to many other neurons, although neurons maintain these activities and Synthesizing a molecule requires energy, but its main function is to receive and send signals, in short, to process information.A similar situation is that a politician is constantly receiving messages from people who want him to vote for or against a measure, and he has to take all of this information into account when he votes.

In the absence of any signal, neurons also typically send background impulses along the axon at a relatively slow, irregular pace.This firing rate is typically 1-5 Hz (1 Hz means one pulse or cycle in one second).This continuous state of "excitable" activity puts neurons on alert and ready to fire more strongly in response to new stimuli.As a neuron receives many exciting signals, making it excited, its firing rate increases to a large value, typically 50-100 Hz or higher.In short time intervals, the firing rate can reach 500 Hz, as shown in Figure 29. There are 500 pulses in 1 second, which sounds fast at first glance, but compared with the processing speed of a home computer, it is extremely slow.If a neuron receives an inhibitory signal, its electrical output may be less than the normal background firing rate.But the reduction is so small that it conveys only relatively little information.Neurons can only transmit one type of signal down the axon.Of course there is no "negative" spike potential.Furthermore, these electrical signals generally travel unidirectionally down the axons from the soma to the terminals of these axons. ①

What do neurons look like?What is it made of?In many ways, neurons are similar to other cells in the human or animal body.Many of its genes are made of DNA located on chromosomes in a specialized structure inside the cell called the "nucleus."There are other special structures inside the cell, which (for example: the mitochondria, the energy base of the cell) have their own DNA.Almost all cells in the body have two copies of genetic information, one from each mother.Each set has about 10 different genes. ② Not all genes are active in all cells.Some are more active in cells of the liver, some are more active in muscle cells, and so on.It is generally believed that genes in various parts of the brain are more active than in any other organ.

Most of these genes encode instructions for the synthesis of some protein or another.If you think of each cell as a factory, proteins are the fast and delicate mechanical tools that keep the factory going.A protein is typically one-billionth the volume of a cell, so small it can't be seen with a light microscope.But its shape (rather than the precise details of its near-atomic structure) can sometimes be seen with an electron microscope.Each protein has its own extremely detailed molecular structure, made up of tens of thousands of atoms linked together in unique ways.The molecules that play a key role in life are built with atomic precision.

Everything in a cell is enclosed within a somewhat fluid lipid membrane that keeps proteins and their products from leaving the cell. Some proteins in the membrane act as sensitive gates or pumps that control the flow of various molecules in and out of the cell.The entire cell structure is made up of those organic molecules with sensitive controls that allow cells to replicate themselves and interact efficiently with other cells in the body. In short, in such a small space, how Such a miraculous chemical reaction is the result of billions of years of evolution by natural selection. Neurons are different from other cells in the body: Mature neurons neither move nor come together and divide normally.If a mature neuron dies, (except very rarely) it is not replaced by a new neuron.Neurons are more spiky in shape than many, many other cells.The branching of neuron dendrites varies with its different types, but it usually has several main branches, and each branch can be divided into several times as many small branches.The cell body (often referred to as the soma) can grow in various sizes, typically about 20 microns in diameter. ①

The most common type of neuron in the neocortex is called a pyramidal cell, which has a slightly pyramid-like cell body with a large number of dendrites at the top, as shown in Figure 30.Other neurons, such as stellate cells, branch in various directions, as shown in Figure 31. The axons (output cables) of neurons can be very long, for example, like your spine can be several feet long, otherwise you can't wiggle your toes (remember that the radius of a neuron cell body is rarely greater than one-thousandth an inch).The diameter of axons that are not surrounded by fat myelin is usually very small, generally in the range of 0.1-1 micron.Axons are coated with fatty myelin, which transmits electrical impulses faster than unmyelinated ones.

Spikes in an axon are not like currents in a wire.In a metal wire, the current is carried by a cloud of electrons.In neurons, there are molecular gates made of proteins on the cell's insulating membrane, and electrical effects depend on those charged ions passing through the molecular gates into and out of the axon.The local potential across the membrane changes due to the back and forth movement of ions.It is this change in electrical potential that is transmitted down the axon.This signal needs to be constantly updated and needs to be supplemented with energy.As a result, the pulse traveling down the axon is not attenuated, and its shape and amplitude are roughly the same at the end as at the point of origin.Such a property allows the spike to have a pronounced effect on the neuron associated with the axon terminal after being transmitted over a long distance.

In the 19th century, it was mistakenly believed that the peak signal travels too fast to be measured, perhaps at the speed of light.This velocity was finally measured by Helmholtz in the middle of the last century, only to find that it rarely exceeded 30 feet per second (this velocity is about one-third of the speed of sound in air).Many people, including Helmholtz's father, were very surprised by this result.For an axon without a fat sheath, its typical speed is 5 feet per second, which seems quite low (in fact, it is lower than the speed of a bicycle), which is equivalent to walking 1.5 millimeters per millisecond.

The distal end of the axon needs to be fed by molecules from the soma, since almost all genes and most of the biochemicals used for protein synthesis are inside the soma, not the axon.There is a bi-directional systematic flow of molecules along the axon.Observing this flow of molecules with a light microscope at high magnification is extremely unusual, showing small particles traveling slowly over each other, some down the axon and some up the cell body; some travel a little faster Some, some not.But all of this flow is much slower than the speed at which the spike signal travels in the axon.Naturally, to direct and control this transport, special molecular components need to be at work.

The classic view of neurons is that the dendrites (input cables) are "passive", meaning that as an electric potential travels from one location on the dendrite to another, it decays.The reason is that some ions leak through the cell membrane, just as a Morse code signal often decays after traveling a considerable distance along a transatlantic cable.For this reason, dendrites are generally shorter than axons, usually only a few hundred micrometers in length.There is now speculation that some neurons also have active processes in dendrites, but they may not be exactly the same as those found in axons. Electrical impulses travel down the axon to the specialized junction between neurons called the synapse.Each neuron has many synapses between its dendrites and cell body.A small neuron has about 500 synapses, and a large pyramidal cell can have as many as 20,000.Each neuron in the neocortex has an average of about 6,000 synapses.Since the spike is electrical and the effect on the next neuron is primarily electrical, it might be assumed that the synapse is also some kind of electrical contact.In fact, some synapses are electrical contacts, but more generally, the transmission of signals between neurons is much more complicated than electrical conduction. In fact, two neurons are not directly connected together.It is easy to see from the photos taken by the electron microscope, as shown in Figure 32, there is a clearly demarcated crack between two neurons, about one-fortieth of a micron wide, this crack is called the synaptic cleft .When an electrical impulse reaches the presynaptic side, it causes small packets of chemicals, called vesicles, to be released into the synaptic cleft.These small chemical molecules diffuse rapidly through the cleft, and some of them bind to molecular gates on the postsynaptic cell membrane, opening these specialized gates and allowing charged particles to flow into or out of the postsynaptic membrane, enabling transmembrane The local potential has changed.The whole process looks like this: Electro-Chemistry-Electricity Generally speaking, the inflow or outflow of ions depends on the concentration of ions inside and outside the neuron.Normally, sodium ions (Na+) are kept at low concentrations within neurons, while potassium ions (K+) are kept at high concentrations within neurons.This is done by special molecular pumps in the cell membrane.If a gate is open and both ions can pass through, sodium ions will flow in and potassium ions will flow out. ① When there are no spikes, neurons have a resting potential across the membrane.This potential is generally -70 millivolts (referring to the inside relative to the outside), a positive potential change on the cell body (for example, the potential reaches -50 millivolts) may cause the cell to fire; and a negative potential change completely prevents it from firing .Whether a neuron can be excited so that it produces a spike on the axon depends mainly on whether these changes in membrane potential (produced by excitatory synapses on dendrites and cell bodies) can cause Changes in regional potential. Let's take a closer look at the structure of the synapse, shown in Figure 33.There are two main types of it in the cortex, called type 1 or type 2.They can be clearly distinguished under an electron microscope. ①In general, he said that type 1 synapses excite the receiving neuron, while type 2 inhibits it. In the brain, most excitatory synapses are not located directly on the main trunk of dendrites, but on some short side branches, as shown in Figure 34, which are called spines.There is never more than one type 1 (excitatory) synapse on a single spine, although some spines also have a single type 2 (inhibitory) synapse.As can be seen in Figure 34, a spine is somewhat like a small flask with its neck glued to the dendrite.The spines have a spherical head (often slightly distorted) and a thin cylindrical neck.The synapse itself, located at its head and somewhat detached from the activity that occurs elsewhere in this cell, has many receptors, including ion gates.If the neurotransmitter molecule (from the synaptic cleft between the synaptic terminal and the spine) is in a specific position on the receptor molecule, the ion gate can be opened. The spine is a rather delicate structure, and its function is far from fully understood.I suspect that spines are a key product of evolution, with which more complex processing of input signals is possible. I do not want to describe the various types of protein molecules in the fatty membrane of neurons.Some of these molecules can be activated by transmitter molecules, ① they are called "receptors".In the neocortex of the brain, the main excitatory transmitter is a fairly common small organic molecule called glutamate. (2) While there are only two main types of ion channels (one sensitive only to voltage and the other only sensitive to neurotransmitters), the most interesting is a third class called "NMDA channels" off the channel. ③It is sensitive to both voltage and glutamate. More precisely, even if there is glutamate, the ion channel is rarely opened when the local membrane potential is at a resting value.Glutamate can open this channel if the membrane potential is elevated (e.g. due to activity at other nearby excitatory synapses).It therefore responds only to a combination of presynaptic activity (due to the release of glutamate from the axon terminal) and postsynaptic activity (due to changes in transmembrane potential due to other inputs).As we shall see, this is a key property of brain function. When the NMDA glutamate channel is open, not only sodium and potassium ions are allowed to pass through, but also an appropriate amount of calcium ions (Ca2+) to pass through, these influxes of calcium ions are like the emergence of such a message that it can trigger a complex chemical chain responses, which are only partially understood, and which ultimately result in changes in the strength of synaptic connections that may persist for days, weeks, months, or even longer periods of time (this may form the basis of a special form of memory—see the Hebbian learning rate described in Chapter 13).We can now explain cognitive processes, such as memory, at the molecular level.An example of an experiment: chemically blocking an NMDA channel in the hippocampus of a mouse, the mouse couldn't remember where it had been. What is the nature of inhibitory synapses?Are there neurons whose axon terminals are excitatory and others inhibitory?Surprisingly, this phenomenon never or rarely occurs in the neocortex.Rather, all the axon terminals of a given neuron are either excited or inhibited, never both.As mentioned above, the neurotransmitter at excitatory synapses is glutamate, whereas at inhibitory synapses the transmitter is the relatively small GABA molecule (1).In the neocortex, approximately one fifth of neurons release the GABA transmitter (2). The fact that most synaptic transmission is chemical rather than electrical has important consequences that some specific small molecules also block it at very low concentrations.This is why a dose of just 150 micrograms of LSD can induce hallucinatory effects.This may also explain why some drugs that reduce mental states under certain conditions, such as depression, seem to be caused by the failure of certain neurotransmitter mechanisms. For example, chemicals in sleeping pills bind to GABA receptors, enhancing Inhibitory function of GABA.This increase in synaptic inhibition is beneficial in promoting sleep.The sedatives chlordiazepoxide and diazepam are also benzodiazepines, which have similar effects. Excitability and inhibition are not symmetrically distributed in the neocortex, but some theoretical models assume they are.Long-distance connections from one area of ​​the cortex to another are made only by pyramidal cells.These cells are excitatory.Most inhibitory neurons have short axons that only affect neurons near it. ① No two neurons with similar morphological structure (there may be very few exceptions) will produce a phenomenon that one is excitatory and the other is inhibitory.The asymmetry of the entire distribution is manifested in at least two aspects: one aspect is that neurons cannot fire negative spike potentials, and the other aspect is that neurons that produce excitation or inhibition belong to different classes.However, all neurons receive either excitatory or inhibitory inputs, possibly to prevent neurons from always resting or firing forever. There are two main classes of neurotransmitters in the neocortex: excitatory glutamate transmitters (or similar substances) and inhibitory GABA transmitters.Unfortunately, things are not that simple, and many other neurotransmitters exist.Those neurons in the brainstem that project to the cortex use serotonin, norepinephrine, dopamine, etc. as transmitters.While other neurons in the brain use acetylcholine as a transmitter, about one-fifth of inhibitory neurons release GABA along with a larger organic molecule called a peptide.Most of these transmitters have slower effects than the two main classes of fast transmitters (glutamate and GABA).They are typically used to modulate the strength of a cell's firing, rather than directly causing it to fire.These transmitters are mainly likely to be involved in more general processes: such as keeping the cortex awake, or remembering something, rather than being involved in the rapid processing of large amounts of complex information. Not only are there multiple neurotransmitters (though only two neurotransmitters do most of the work), but there are also multiple ion channels.There are at least seven different types of potassium channels, and most are fairly common. ②Some channels open quickly, while others open slowly; some channels lose their activity quickly once opened, and some close more slowly: some channels mainly transmit electrical impulses on axons, while others produce more delicate electrical impulses on cell bodies and dendrites effect.In order to calculate the exact behavioral changes of a neuron in response to an input signal, we need to know the distribution and properties of all ion channels of this neuron. Different neurons have different firing patterns.Some neurons fire very quickly, others very slowly; some neurons fire single spikes, while others tend to fire in clusters.In some cases, the same neuron can fire in either of the above two ways, mainly depending on its activity state and current behavior.The pattern of neuron firing is different when animals are in slow-wave sleep (a state of deep sleep without dreams) and when they are awake. The main reason is that neurons in the brainstem have different effects on the thalamus and neocortex.What we ultimately need is a deeper and more comprehensive understanding of the information processing of various types of neurons. On the surface, a neuron appears remarkably simple, responding to numerous inputs by sending a train of electrical impulses down its axon.Only when we try to characterize exactly how it responds, how this response changes over time, and how it changes with the state of other parts of the brain, do we really encounter the inherent complexity of neurons. sex.Obviously, we need to understand how these chemical and electrical processes interact, and then we need to take away the specific details of these processes and treat them in an approximate, operational way.In short, we need to build simplified models of various types of neurons that are neither too complex to manipulate nor so simple that they ignore important properties.This is easier said than done.A single neuron is kind of dumb, it can express its meaning in a very clever way. A rather obvious property of neurons is that individual neurons have different firing rates, and in some ways, different firing patterns.Still, neurons can only send so much information at any one time.However, the potential information obtained by neurons through many, many synapses during this time is very large.When we look at a neuron in isolation, this conversion process between input and output is bound to lose information.However, this loss of information can be compensated in that each neuron responds to a specific combination of inputs and transmits this new form of information, not to just one place, but to many places.Thus, because of the many branches on a single axon, electrical impulses traveling down the axon are distributed in the same pattern across different synapses.A neuron receives the same information at one of its synapses as many other neurons receive.All this shows: At a certain moment, we cannot only consider a single neuron alone, but must consider the combined effect of many neurons. It is important to recognize the fact that one neuron can simply tell another neuron how excited it is. ① These signals do not give other information to the receiving neurons, such as the position of the first neuron, etc. ② The information in this signal is usually linked to some activity in the external world, for example, the signal received by the photoreceptors of the eye. Sensually, what the brain gets is usually information about the outside world or other parts of the body.That's why the things we see are located outside of us, even though the neurons responsible for "seeing" are located in the brain, and for many people, it's an ingrained notion that the "world" is located outside their bodies, Yet from another perspective (as they know it), the world is entirely inside their heads.This is also true for your body, what you know about it is not attached to your head, but is located in your brain. Of course, if we open the skull and take out the signal emitted by a certain neuron, we can generally determine the location of the neuron.But the brains we're studying don't know this information.This explains why, under normal circumstances, we cannot know exactly where in the brain perception and thought occur.No such neuron exists to encode this kind of information. Recall that Aristotle believed that these processes took place in the heart, because he could both know the location of the heart and observe some mental processes. But this transmission is too slow to carry fast information.Changes in behavior that occur during a relationship.We cannot do similar experiments on neurons in the human brain without special equipment.These and others will be covered in the next chapter. ①I will focus on the "typical" neurons found in vertebrates (like humans), which are almost indistinguishable from invertebrates (such as insects). ① For artificial neural networks, signals can be transmitted in the opposite direction, which is called reverse. ① Red blood cells are an exception. ② Its more precise number is not yet known, but it may be known by about 2000. ① Its volume is about 1000 times larger than that of a bacterial cell such as Escherichia coli (E.Coli). (1) This explanation is oversimplified, because the flow of hyperons also depends on the potential difference across the membrane. ① Type 1 synapses have round vesicles, while type 2 vesicles are usually oval or flat. Type 2 is more symmetrical than type 1, and its synaptic cleft is smaller. (l) Some respond only to changes in transmembrane voltage, and some respond only when certain small molecules—neurotransmitters—are bound to proteins outside the membrane.Some proteins have ion channels that open rapidly to allow ions to pass through, and some do not.They produce slow effects through indirect means in cells, and they are mysterious second messengers. ② Glutamic acid is one of the twenty amino acids that make up protein, and it is sometimes used to add flavor to food. ③The gene of this kind of receptor has been isolated. ① There are two main types of GABA receptors. Type A is a fast ion channel that allows chloride ions to pass through. Type D receptors are slower and are the pathway of the second messenger system. ②When mature, such neurons have few or no spines on the dendrites, and their synapses are located directly on the dendrites or the cell body.They generally fire faster than spine-bearing excitatory neurons.There are several rather different types of inhibitory neurons, but describing them in detail is beyond the scope of this book. ① There is a kind of "basket cell" that can have a rather long inhibitory connection in a certain cortical area. ② For example.A potassium ion channel, called IC, is activated by internal concentrations of calcium ions. ① In addition to the coded average issuance rate, the issuance pattern may also contain other information. ② neurons can send chemical signals along the axon.In some cases, they can convey additional information.