and Function of Neurons

Transcription

1 CHAPTER 1 Structure and Function of Neurons Varieties of neurons General structure Structure of unique neurons Internal operations and the functioning of a neuron Subcellular organelles Protei n synthesis Neuronal transport: shipping and receiving molecules and organelles throughout the neuron Summary prise tens of billions of neurons, each linked to thousands of other neurons. Thus, Neurons the brain arehas the cells trillions of chemical of specialized communication connections in the known brain. ashuman synapses. brains Neurons com have many sizes, lengths, and shapes, which determine their functions. Localization within the brain also determines function. When neurons malfunction, behavioral symptoms may occur. When drugs alter neuronal function, behavioral symptoms may be relieved, worsened, or produced. Thus, this chapter briefly describes the structure and function of normal neurons as a basis for understanding psychiatric disorders and their treatments. Varieties of neurons General structure Although this textbook will often portray neurons with a generic structure (such as that shown in Figure l-ia and B), the truth is that many neurons have unique structures (see Figures 1-2 through 1-8). All neurons have a cell body, known as the soma, and are set up structurally to receive information from other neurons through dendrites, sometimes via spines on the dendrites, and often through an elaborately branching "tree" of dendrites (Figure 1-1A and B). Neurons are also set up structurally to send information to other neurons via an axon, which forms presynaptic terminals as the axon passes by - "en passant" (Figure l-la) - or as it ends (in presynaptic axon terminals) (Figure l-ia). Structure of unique neurons Many neurons in the central nervous system have unique structures. For example, each pyramidal cell has a cell body shaped like a triangular pyramid (Figure 1-2A is a somewhat Structure and Function of Neurons I 1

2 dendrites cell body (soma) dendritic spines dendritic tree /' axon o ) presynaptic axon terminals en passant presynaptic axon terminals A general structure of the neuron B another general structure of the neuron FIGURE l-ia and B Generic structure of neuron. This is an artist's conception of the generic structure of a neuron. All neurons have a cell body known as the soma, which is the command center of the nerve and contains the nucleus of the cell. All neurons are also set up structurally to both send and receive information. Neurons send information via an axon, which forms presynaptic terminals as it passes by (en passant) or as it ends (A). Neurons receive information from other neurons through dendrites, sometimes via spines on the dendrites, and often through an elaborately branching tree of dendrites (B). Although all neurons share these properties, they can have unique structures that, in turn, dictate specialized functions. realistic depiction and 1-2B is an icon of a pyramidal cell); each also has an extensively branched spiny apical dendrite and shorter basal dendrites (Figure 1-2B) as well as a single axon emerging from the basal pole of the cell body. Pyramidal neurons are discussed extensively in this textbook because they make up most of the neurons in the functionally important prefrontal cortex as well as elsewhere in the cerebral cortex. Several other neurons are named for the shape of their dendritic tree. For example, basket cells are so named because they have widely ramified dendritic trees that look rather like baskets (Figure 1-3A is a somewhat realistic depiction and 1-3B is an icon of a basket cell). Basket cells function as interneurons in the cortex, and the wide horizontal spread of their axons can make many local inhibitory contacts with the soma of other cortical neurons. Double bouquet cells are also inhibitory interneurons in the cortex and have a very interesting vertical bitufted appearance, almost like two bouquets of flowers (Figure 1-4A is a somewhat realistic depiction and 1-4B is an icon of a double bouquet cell). Each double bouquet cell has a tight bundle of axons that is also vertically oriented, with varicose collaterals that innervate the dendrites of other cortical neurons, including other double bouquet cells, and supply inhibitory input to those neurons. Spiny neurons, not surprisingly, have spiny-looking dendrites (Figure I-SA 2 I Essential Psychopharmacology

3 motor cortex pyramidal cell body (soma) "" basal dendrites recurrent collateral (axon) axon / axon / _ presynaptic axon terminal _ presynaptic axon terminal A realistic pyramidal cell B icon of pyramidal cell FIGURE 1-2A and B Pyramidal cells. Pyramidal cells (depicted somewhat realistically in A and iconically in B) have a cell body shaped like a triangular pyramid, an extensively branched spiny apical dendrite, shorter basal dendrites, and a single axon emerging from the basal pole of the cell body. The majority of the neurons in the cerebral cortex, particularly in the prefrontal cortex, are pyramidal neurons. is a somewhat realistic depiction and 1-5B is an icon of a spiny neuron). Spiny neurons are located in the striatum in large numbers and have a highly ramified dendritic arborization that radiates in all directions and, of course, is densely covered with spines, which receive input from cortex, thalamus, and substantia nigra. Spiny neurons have long axons that either leave the striatum or circle back as recurrent collaterals to innervate neighboring spiny neurons. Finally, Purkinje cells from the cerebellum form a unique dendritic tree that, in fact, looks very much like a real tree (Figure 1-6). This dendritic tree is extensively branched and fans out from an apical position, with a single axon emerging from the basal pole of the cell. At least one type of neuron is named for its unique axonal structure: the chandelier neuron (Figure 1-7A is a somewhat realistic depiction and 1-7B is an icon of a chandelier neuron). The axons of this cell look like an old-fashioned chandelier, with odd-appearing axon terminals shaped like vertically oriented cartridges, each consisting of a series of axonal swellings linked by thin connecting pieces. Chandelier neurons are yet another type of inhibitory interneuron in the cortex, where the characteristic "chandelier" endings of their axons have a specific function and location - namely, to serve as inhibitory contacts close to the initial segment ofaxons of pyramidal cells. Thus, chandelier neurons terminate in what Structure and Function of Neurons I 3

4 '\/ presynapticaxon terminals A realistic basket cell B icon of basket cell FIGURE 1-3A and B Basket neurons. Basket neurons are named for their widely ramified dendritic trees, which resemble baskets (depicted somewhat realistically in A and iconically in B). They are cortical interneurons with axons that spread horizontally to make many inhibitory contacts with the soma of other neurons presynaptic axon terminal...cell body bouquet shape of dendritic tree ;! bouquet shape of dendritic tree ". presynaptic axon terminal A realistic double bouquet cell B icon of double bouquet cell FIGURE 1-4A and B Double bouquet cells. Double bouquet cells are so called because of their vertical bitufted appearance, which resembles two bouquets of flowers (depicted somewhat realistically in A and iconically in B). Like basket neurons, double bouquet cells are inhibitory interneurons in the cortex. They have a tight bundle of axons that is oriented vertically, with varicose collaterals that innervate the dendrites of other cortical neurons, including other double bouquet cells. 4 I Essential Psychopharmacology

5 spiny neuron cell body /' presynaptic axon terminal -J spiny dendrites /' presynaptic axon terminal A realistic spiny neuron B icon of spiny neuron FIGURE I-SA and B Spiny neurons. The dendrites of spiny neurons radiate in all directions and are densely covered with spines (depicted somewhat realistically in A and iconically in B). Spiny neurons are located in the striatum in large numbers and receive input from cortex, thalamus, and substantia nigra. The axons of spiny neurons are long and either leave the striatum or circle back as recurrent collaterals to innervate neighboring spiny neurons, FIGURE 1-6 Purkinje cells. Purkinje cells from the cerebellum have extensively branched dendritic trees fanning out from an apical position, with a single axon emerging from the basal poll of the cell, '2 k" / unique Pur InJe /' dendritic tree cell body presynaptic /axon terminal Purkinje cell is called an axoaxonic synapse. Since the initial segment of a pyramidal cell's axon is the most influential location in determining whether that axon will fire or not, the chandelier neuron can potentially provide the most powerful inhibitory input to a pyramidal neuron, possibly even being able to completely shut down a pyramidal cell's firing. Many chandelier Structure and Function of Neurons I 5

6 chandelier axon /terminals axon A realistic chandelier neuron B icon of chandelier neuron FIGURE 1-7A and B Chandelier neurons. The chandelier neuron is named for its unique axonal structure (depicted somewhat realistically in A and iconically in B). The axons resemble an old-fashioned chandelier with axon terminals shaped like vertically oriented cartridges, each consisting of a series of axonal swellings linked together by thin connecting pieces. Like basket neurons and double bouquet cells, chandelier neurons are inhibitory interneurons in the cortex. The "chandelier" endings of their axons come into close contact with the initial segments of pyramidal cell axons, forming what is called an axoaxonic synapse. The chandelier neuron can potentially provide powerful inhibitory input to a pyramidal neuron via this synapse, possibly even completely shutting down a pyramidal cell's firing. Many chandelier neurons provide input to a given pyramidal cell, and each chandelier neuron can provide input to several pyramidal cells. neurons provide input to a given pyramidal cell, and each chandelier neuron can provide input to several pyramidal cells. Internal operations and the functioning of a neuron Subcellular organelles In order to do its duties, the neuron contains various internal working parts that have specialized functions, from subcellular organelles and protein synthetic machinery to internal superhighways for transport of these materials into dendrites and axons on specialized molecular "motors." Specific neuronal functions are associated with each anatomical zone of a neuron (Figure 1-8). For example, the soma and dendrites together form the somatodendritic zone, which has the function of "reception." Neurons receive a wide variety of signals, sometimes simultaneously and sometimes sequentially, from other neurons, environment, chemicals, hormones, light, drugs, and so on. In addition to receiving this mass of incoming information, the somatic zone also serves as a "chemical integrator" of it all. It does this 6 I Essential Psychopharmacology

7 General Structure and Function of the Neuron Structure Function somatodendritic zone reception somatic zone integration chemical encoding zone initial segment synapse elements -- output propagation encoding signal electrical signal signal o I I 0 I presynaptic I I presynaptic I presynaptic zone zone zone n axonal D axon hillock FIGURE 1-8 Anatomic zones of neurons. The different anatomic zones of neurons are associated with specific functions, as shown here. The soma and dendrites form the somatodendritic zone, which has the function of receiving a wide variety of signals from other neurons. The somatic zone also serves as a chemical integrator of incoming information: incoming signals from postsynaptic dendrites are decoded by the genome (located in the cell nucleus in the soma), which then encodes chemical signals destined for either internal or external cornmunication. The initial segment of the axon, the axon hillock, serves as an electrical integrator, controlling whether or not the neuron will fire in response to incoming electrical information. The axon propagates these signals, with electrical signals traveling along the membrane of the axon and chemical signals traveling within its internal structural matrix. The presynaptic zone at the end of the axon contains unique structures that convert chemical and electrical signals into signal output. by first generating cascades of incoming chemical signals from its postsynaptic dendrites, which speak directly with its genome, located in the cell nucleus in the soma (Figure 1-8). These incoming volleys of chemical information are then decoded and read by the genome, after which the genome adds its own reaction to this information by encoding chemical Structure and Function of Neurons I 7

8 nucleus anterograde motor RNA Golgi apparatus polysomes retrograde motor mitochondrion peptide/ neurotransmitter rough endoplasmic secretory granule synaptic vesicle reticulum -- - microtubule neurofilaments cytoskeleton Iysosomes -pre-/postsynaptic density retrograde vesicle FIGURE 1-9 Neuronal components. Depicted here are many neuronal components manufactured by the cell nucleus, which contains the neuron's DNA. These components are located in specific locations within the neuron and have specific functions. signals destined either for internal communication within its own neuronal boundaries or for external communication via its neuronal connections. Another anatomical zone is that of the axon hillock, also called the axon's initial segment (Figure 1-8). Its job is to serve as an "electrical integrator" of all the incoming electrical information and decide whether or not to "fire" the neuron. Directly connected to the axon hillock is the axon itself, which propagates electrical signals along its membrane and chemical signals within its internal structural matrix. At the end of the axon is a specialized zone with unique structures that allow it to convert the chemical and electrical signals arriving there into signal output to the next neuron. How does all of this happen? It is done by orchestrating many specialized neuronal instruments to work together in amazing functional harmony - at least when things are working normally. Many components of a functioning neuron are shown in Figure 1-9. A representation of where these components are localized within the neuron is shown in Figure These specialized neuronal instruments are put into action in the remaining figures of this chapter (Figures 1-11 through 1-20). The specific roles thatthese specialized neuronal instruments play in neuronal functioning as shown in these figures are explained briefly here. As already mentioned, the cell nucleus, containing the neuron's DNA, is located in the neuron's soma and is responsible for manufacturing essentially all the components shown 8 I Essential Psychopharmacology

9 Localization of Subcellular Organelles synaptic vesicles presynaptic density FIGURE 1-10 Localization of neuronal components. The function of each neuronal component is unique; in addition, each component is distributed differently throughout the neuron, as shown here. Thus, different parts of the neuron are associated with different functions. For example, DNA transcription occurs only in the soma, while protein synthesis, which involves polysomes and endoplasmic reticulum, occurs both in the soma and in dendrites. Structure and Function of Neurons 9

10 Synthesis of a Cytoplasmic/Peripheral Protein: Ready for Transport ". free 'Ji{fT W Udd nucleus>... ns \' <cp, A./ polysomes R ;1 pripheral protem FIGURE 1-11 Protein synthesis. Most of the structural and regulatory molecules of a neuron are proteins. When DNA is transcribed into RNA, it is read by one of two types of ribosomes: free polysomes, which are not membrane bound, or rough endoplasmic reticula, which are membrane bound. Proteins are then synthesized on/within the ribosomes. Peripheral proteins, which are soluble and live in the cytoplasm, are synthesized on free polysomes and transported directly into the dendrites and axons. in Figures 1-9 and As can be seen from Figure 1-10, these components have specific locations within the neuron's specialized structure; therefore some functions occur in one part of the neuron but not another. For example, all the nuclear DNA is transcribed in the soma but all protein synthesis does not occur there, because the synthetic machinery of polysomes and endoplasmic reticulum exists in dendrites as well as the soma but not to any great extent in axons (Figure 1-10). The vital function of transport occurs in both axons and dendrites, but there are more microtubules for transport in dendrites and more neurofilaments for transport in axons (Figure 1-10). Cytoskeletal support proteins exist along the membranes of the entire neuron, but postsynaptic density proteins exist only in dendrites and soma membranes and at the beginning and end ofaxons, whereas presynaptic density proteins exist only in axon terminals (Figure 1-10). 10 I Essential Psychopharmacology

11 Synthesis of Integral Membrane and Secretory Proteins and Peptides: Packaged for Transport "'J nucleus """" genes I,.! 666 t(fdna/ '-rv endoplasmic mrna'" Ir-J rough reticulum. FIGURE 1-12 Peptide synthesis. Integral or secretory proteins, or peptides, are proteins that are inserted into a membrane. They are produced when mrna is read by the rough endoplasmic reticulum, which synthesizes these proteins and packages them into vesicles to be sent to the Golgi apparatus. The proteins are then modified within the Golgi apparatus and packaged into secretory vesicles ready for transport. \ 3 '2 Protein synthesis Few neuronal functions are more important than the synthesis of proteins, which are produced as the result of gene activation. Because most of the important structural and regulatory molecules of a neuron are proteins, they functionally carry out orders from the genome. For example, proteins become the building blocks when the genome orders a new synapse to be made; proteins are the receptors and enzymes of the neuron; proteins can activate messengers or synthesize anything the neuron needs. Thus, it is no surprise that the neuron is organized so that high priority can be given to making and transporting various proteins. Proteins are synthesized on a subcellular organelle known as a ribosome. When DNA is transcribed into RNA, the RNA can be read by either of two types of ribosomes in order for proteins to be synthesized. One type are called free polysomes, because they are not membrane-bound. The other type are membrane bound and are called rough endoplasmic reticulum, or "Nissl substance." Protein synthesis occurs predominantly in the soma (Figures 1-11 and 1-12). Proteins that are soluble, and thus live in the cytoplasm, are synthesized on Structure and Function of Neurons I 11

12 secretory protein FIGURE 1-13 Dendrite protein synthesis. Mostproteinsynthesisoccurs in the soma; however,some protein synthesisoccurs in dendrites.mrnais somehow made accessible, perhapsvia microtubules,to free polysomes and roughendoplasmicreticulalocatednear dendriticspines, whichthen synthesizeproteinslocally. free polysomes and then transported directly into dendrites and axons, wherever they are needed (Figure 1-11). These are called peripheral proteins. Proteins that are destined for insertion into a membrane, called integral or secretory proteins or peptides, are synthesized within the rough endoplasmic reticulum, packaged there into vesicles, and shipped to the Colgi apparatus, which modifies and molecularly "decorates" these proteins; finally, they exit the Colgi apparatus in secretory vesicles, ready for transport (Figure 1-12). Some protein synthesis occurs in dendrites (Figure 1-13). Presumably these proteins are necessary for implementing those specialized functions unique to dendrites, such as receiving information, forming postsynaptic signal reception and signal transduction machinery, and the like. Polysomes are located in dendrites, often close to dendritic spines. RNA formed in the soma is somehow accessible to these polysomes in the dendrites, so that proteins can be synthesized locally where they would be ready for action immediately upon synthesis, as they would not need transport into the dendrite. Neuronal transport: shipping and receiving molecules and organelles throughout the neuron Much of the neuron functions like a busy depot. Following the manufacture of protein and organelles, these components must be packaged and shipped. Some must be dispatched with the speed of an "overnight" delivery system (fast transport), whereas others are sent with the deliberation of "snail mail" (slow transport). The various transport systems up and down axons and dendrites form a type of neuronal infrastructure of roads and bridges to get every component where it must go and when it must get there. For example, cytoplasmic proteins are sent into both axons and dendrites by a slow transport system (Figure 1-14). This system is really slow, moving only about 2 mm a day, or 50 to 100!Jm an hour. Slow transport motors (indicated by a tortoise carrying the soluble proteins in Figure 1-14) crawl 12 i EssentialPsychopharmacology

13 Slow Transport of Cytoplasmic Proteins cytoplasmic protein slow transport motor cytoskeleton FIGURE 1-14 Slow transport of proteins. Once proteins and organelles have been made, they must be transported to their ultimate destination. This can occur via one of two delivery systems: slow transport or fast transport. Cytoplasmic proteins are sent via slow transport motors (depicted here as tortoises) that crawl along the cytoskeleton at a rate of 2 mm per day, or 50 to 100 ILm an hour. along the cytoskeleton and slowly yet inexorably deliver these proteins to both axonal and cytoplasmic destinations. Interestingly, the infrastructure system itself is also transported via this slow transport system (Figure 1-15). Thus, microtubules are transported slowly into dendrites and axons and neurofilaments are transported into axons (Figure 1-15) to form the very highways upon which other components are rapidly transported through the fast transport systems, which are shown in Figures 1-16 though / Structure and Function of Neurons I 13

14 Slow Transport of Microtubules and Cytoskeleton FIGURE 1-15 Slow transport of microtubules and neurofilaments. Slow transport is also the deliverysystem used for movingthe organelles involvedin fast transport. Thus, microtubulesare deliveredto dendritesand axons and neurofilaments are deliveredto axonsvia slowtransport. slowtransportmotor fasttransportmotor cytoplasmic protein cytoplasmic enzyme microtubule cytoskeleton neurofilament Many neuronal materials are passengers that ride on fast transport systems with fast transport motors, which are shown as hares in Figure Such passengers include mitochondria, synaptic vesicles containing neurotransmitters, secretory vesicles containing secretory proteins, and all sorts of other proteins, from receptors to enzymes to ion channels to transport pumps and many more. Transport of these materials allows supplies depleted during the normal conduct of neuronal business by dendrites and axons to be replenished. A fast transport system (indicated by "hares" in Figures 1-17 through 1-20) carries membrane-bound secretory vesicles full of secretory proteins at about 200 mm per day, but only from the soma to the axon terminal, a direction known as "anterograde" and designated in Figure 1-17 as "southbound lanes." There is also transport in the opposite direction, known as "retrograde" and designated in Figure 1-18 as "northbound lanes." However, 14 EssentialPsychopharmacology

15 Types of Materials for Fast Transport mitochondria receptors synaptic vesicles enzymes growth factor.....::::.. ion channels anterograde secretory vesicles <q o neurotransmitter peptide neurotransmitters retrograde secretory vesicles oldgrowth mitochondrion factor reuptake pumps (neurotransmitter transporters) peptides FIGURE 1-16 Materials for fast transport. Passengersof fast transport systems includemitochondria,synaptic vesiclescontainingneurotransmitters,secretoryvesiclescontainingsecretoryproteins,receptors,enzymes,ion channels, reuptake pumps, and other proteins. retrograde transport is about half as fast and includes the return of used and discarded proteins and organelles from the axon terminal, which are shipped up to the soma for destruction in lysosomes. Also, the retrograde system takes up growth factors and viruses from the synapse and sends them up to the soma, where they can signal the genome chemically (Figure 1-18). Another fast transport system carries the machinery for synthesizing, metabolizing, and utilizing neurotransmitters. In the case oflow-molecular-weight neurotransmitters such as monoamines, this includes all of their synthetic machinery, since these neurotransmitters are not only manufactured in the soma and shipped to the axon terminal but are also made locally in the axon terminal from synthetic enzymes shipped there (Figure 1-19). This is important, because the rate of utilization of these neurotransmitters can be greater than the rate at which they can be shipped all the way from the soma, even on a "fast" transport system. Neurotransmitter is thus packaged and stored in the presynaptic neuron in vesicles, like a loaded gun, ready to fire. Since a reuptake pump (monoamine transporter), which can recapture released monoamines, is present on the presynaptic neuron, monoamines used in one neurotransmission can be captured for reuse in a subsequent neurotransmission. This is in contrast to the way in which neuropeptides function in neurotransmission (Figure 1-20). That is, higher-molecular-weight peptides are synthesized only in the soma and are not taken back up into the presynaptic neuron by a reuptake pump. Fortunately, peptide Structureand Functionof Neurons I 15

16 tr.c.", '000""'"' "' I, mitochondrion '" "! synaptic vesicle 200 Limit receptor slow anterograde tast enzyme transport transport vesicle microtubule motor motor cytoskeleton " 0 ion channel I bh m0 FIGURE 1-17 Fast anterograde transport. Shown here is delivery of various neuronal components to their axonal destinations via fast transport. Membrane-bound secretory vesicles full of secretory proteins are transported at a rate of 200 mm per day from the soma to the axon terminal in a direction known as anterograde (depicted here as southbound lanes). 16 I Essential Psychopharmacology

17 fast transport motor lysosome old mitochondrion Northbound Lanes Speed Limit 100 mm/day old synaptic vesicle o retrograde vesicle :-:. growth factor microtubule cytoskeleton FIGURE 1-18 Fast retrograde transport. Fast transport also occurs in the opposite direction at 100 mm per day; this is known as retrograde transport (designated as northbound lanes here). With retrograde transport, used and discarded proteins and organelles are brought from the axon terminal to the soma, where they are destroyed by Iysosomes. In addition, growth factors and viruses from the synapse are sent to the soma, where they can signal the genome chemically. Structure and Function of Neurons 17

18 00 m SPEED mm/day LIMIT 0 CD (I W last transport motor serotonin amino acid decarboxylase oxidasesynaptic monoamine vesicle I L1 fi tryptophan hydroxylase FIGURE 1-19 Fast transpdrt: low-molecular-weight neurotransmitter machinery. Another fast transport system carries the machinery for synthesizing, metabolizing, and utilizing neurotransmitters. Because the synthetic enzymes involved in manufacturing low-molecular-weight neurotransmitters such as monoamines are transported to the axon terminal, these neurotransmitters can be made both in the soma and locally in the axon terminal. In addition, reuptake pumps can recapture released neurotransmitters for reuse in subsequent neurotransmission. This is important because the rate of utilization of these neurotransmitters can be greater than the rate at which they can be shipped from the soma. 18 I Essential Psychopharmacology

19 .DAd-,mRN\A,,{;f P1"" ':--<'?[ f ( 'It'.,. pmpm- peptide prepropeptide / / gene mrna., I prepropeptide propeptide inactive peptide, 0 endoplasmic converting catabolic metabolite! peptidase core enzyme reticulum vesicle fast transport motor 100 large dense- a:::::> c:::::::> i!:. " FIGURE 1-20 Fast transport: larger neuropeptide machinery. Unlike low-molecular-weight neurotransmitters, larger neuropeptides are synthesized only in the soma and are not taken back up into the presynaptic neuron by a reuptake pump. However, peptide neurotransmitters are generally released more slowly, allowing transport of these neurotransmitters from the soma in larger dense-core vesicles to keep up with demand. Structure and Function of Neurons I 19

20 Summary neurotransmitters are generally released more slowly, so that transport of these neurotransmitters from the soma in larger dense-core vesicles can keep up with demand (Figure 1-20). This chapter has described the structure and function of various types of neurons. Although all neurons share some structural similarities, there are many unique aspects to some neurons, including the shapes of their somas, dendritic trees, and axons. This chapter has also reviewed how the various components of a neuron work together to carry out specialized functions, such as synthesis of important neuronal proteins and transport of proteins and other vital supplies throughout the neuron. An understanding of the structure and function of normal neurons can provide a good background for grasping what goes wrong with neurons in various psychiatric disorders and how drugs affect neurons to treat various psychiatric disorders. 20 Essential Psychopharmacology