Chapter 9 – Synapse Structure

Figure 9.1

This simplified diagram shows the basic synaptic contact between two neurons. A presynaptic cell is shown on the left making synaptic contact with a postsynaptic cell on the right. The postsynaptic neuron displays typical neuronal features including dendrites, cell body, and a myelinated axon with gray myelin segments. The synapse is highlighted with green coloring at the contact point, emphasizing where the presynaptic terminal forms synaptic connections with the postsynaptic cell membrane. This illustrates the fundamental principle of neuronal communication through synaptic contacts.

Animation 9.1

The animation illustrates the direct transfer of ions across an electrical synapse between a presynaptic neuron on the left and a postsynaptic neuron on the right. The two cell membranes run vertically down the center of the screen in close proximity, connected by a series of stacked, teal-colored channel proteins. At the bottom of the screen, reference diagrams label a single membrane channel as a connexon and the paired, aligned channels bridging both membranes as a gap junction. Initially, numerous spheres representing sodium are concentrated in the cytoplasm of the presynaptic neuron on the left, while only a few are scattered in the postsynaptic neuron on the right. As the animation progresses, the sodium spheres move smoothly and sequentially from left to right, passing directly through the open pores of the teal gap junctions to enter the postsynaptic cytoplasm. The visual demonstration emphasizes how these continuous pathways allow a direct, passive flow of sodium ions between connected cells without the need for intermediate chemical messengers.

Animation 9.2

The animation illustrates the structural basis for bidirectional signaling across an electrical synapse. The visual layout features two vertical cell membranes separated by a narrow gap, bridged down the center by a series of stacked, teal-colored gap junction channels. Labels at the bottom identify a single membrane channel component as a connexon and the completed pathway spanning both membranes as a gap junction. Spheres representing sodium ions are distributed in the cytoplasm on both the left side, labeled as the presynaptic neuron, and the right side, labeled as the postsynaptic neuron. The animation highlights that the teal gap junction channels are entirely symmetrical and open on both ends, creating an unobstructed physical bridge between the cells. Rather than forcing a single direction of travel, this open architecture allows sodium ions to move freely through the pores in either direction, demonstrating that the actual route of the signal is dictated solely by which neuron has the stronger electrochemical gradient at any given moment.

Animation 9.3

The animation illustrates the movement of metabolic and signaling molecules through an electrical synapse. The visual architecture displays a presynaptic neuron on the left and a postsynaptic neuron on the right, separated by a thin physical gap that is bridged down the center by a series of open, teal-colored gap junction channels. Scattered throughout the cytoplasm on both sides are numerous spheres representing sodium ions, interspersed with larger, distinct geometric shapes that represent complex cellular molecules. These molecules are explicitly labeled on screen as orange rectangles for cAMP, green rectangles for ATP, and yellow rectangles for IP3. As the animation plays, these larger molecules, along with the smaller sodium ions, are shown drifting passively back and forth through the wide, unobstructed pores of the teal gap junctions. The visual demonstration emphasizes that the physical clearance inside these channels is large enough to accommodate complete signaling molecules, allowing adjacent cells to achieve direct metabolic and biochemical coupling.

Figure 9.2

The diagram illustrates the anatomical components of a typical chemical synapse, showing a distinct separation between a presynaptic terminal on the left and a postsynaptic membrane on the right. The presynaptic terminal is a large, rounded axonal ending that contains numerous small, circular structures representing synaptic vesicles filled with chemical neurotransmitter molecules. Separating the presynaptic terminal from the target cell is a clear, narrow horizontal gap labeled as the synaptic cleft, highlighting that the two neurons share no direct physical or cytoplasmic connection. Directly across the cleft, the postsynaptic membrane is lined with specialized, embedded protein complexes representing neurotransmitter receptors. This layout visually emphasizes the unidirectional nature of chemical transmission, where signals must be converted from electrical activity into chemical messengers to cross the structural divide.

Animation 9.4

The animation illustrates the visual sequence of neurotransmitter release at a chemical synapse, followed by a conceptual review question. The visual layout displays a presynaptic cell terminal on the left and a postsynaptic cell membrane on the right. A legend at the bottom defines a blue circle as a neurotransmitter and a purple curved crescent as a receptor. Inside the presynaptic cell, two circular synaptic vesicles are shown holding several blue neurotransmitter spheres. As the animation plays, these vesicles move forward and fuse directly with the boundary of the presynaptic membrane. Upon fusing, the vesicles open up to release the blue spheres into the synaptic cleft, where they diffuse across the open gap to bind onto the purple receptors embedded along the postsynaptic membrane. The video concludes by transitioning to a static text frame displaying a multiple-choice question that asks which statements are true regarding electrical and chemical synapses, listing options about signal transmission speed and the allowance of flow.

Figure 9.3

This three-panel diagram illustrates the different locations where chemical synapses can form based on the specific region of the postsynaptic neuron contacted by the presynaptic terminal. Each panel shows a presynaptic cell on the left with its axon extending and branching, represented as a series of gray segments forming a myelinated axon. The postsynaptic cell is shown on the right with its characteristic neuronal structure including a cell body, dendrites, and an axon. In Panel A, representing an axodendritic synapse, the presynaptic axon terminal forms synaptic connections directly with the dendrites of the postsynaptic neuron, which are highlighted in green. In Panel B, representing an axosomatic synapse, the presynaptic terminal makes direct contact with the cell body of the postsynaptic neuron, which is highlighted in green. In Panel C, representing an axoaxonic synapse, the presynaptic terminal forms synaptic connections with the initial segment or shaft of the axon of the postsynaptic neuron, highlighted in green. All three configurations demonstrate the spatial diversity of chemical synaptic connections, with the location of the synapse potentially affecting how incoming signals are integrated by the postsynaptic cell.

Chapter 10 – Neurotransmitter Synthesis and Storage

Figure 10.1

This figure organizes small molecule neurotransmitters by chemical structure through four sections. At the top left, acetylcholine stands alone, showing an ester linkage connecting an acetyl group to a choline group with a quaternary amine. The left panel labeled “Amino acid transmitters” contains three structures: glutamate (a five-carbon chain with two carboxyl groups and an amine), GABA (a four-carbon chain with one carboxyl group and an amine), and glycine (the simplest amino acid with a two-carbon backbone). The top right panel labeled “Biogenic amines” shows serotonin (containing an indole ring structure with a hydroxyl group and an ethylamine side chain) and histamine (containing an imidazole ring with an ethylamine side chain). The bottom right panel labeled “Catecholamines” (a subgroup of biogenic amines) displays three structurally related molecules: dopamine (a benzene ring with two hydroxyl groups—a catechol ring—and an ethylamine chain), norepinephrine (dopamine with an additional hydroxyl group on the side chain), and epinephrine (norepinephrine with a methyl group on the amine). This classification system groups neurotransmitters by shared chemical features that relate to their synthesis pathways and metabolic enzymes.

Figure 10.2

This figure shows acetylcholine synthesis and storage in a presynaptic terminal. The terminal is depicted as a rounded structure containing cellular machinery. At the top left, two precursor molecules (acetyl CoA and choline) enter the terminal. These substrates are converted by the enzyme choline acetyltransferase (ChAT), shown as a green oval, into acetylcholine. The enzyme name appears in purple text. The synthesized acetylcholine molecule is shown with its chemical structure below, displaying the characteristic ester linkage. On the right side of the terminal, two synaptic vesicles contain acetylcholine molecules (blue circles). A single acetylcholine molecule with an arrow indicates loading into vesicles via the vesicular acetylcholine transporter (VAChT), labeled on the right. This illustrates how acetylcholine is synthesized in the cytoplasm and then packaged for storage and release.

Figure 10.3

This figure illustrates glutamate synthesis and storage in a presynaptic terminal. The terminal is shown as a rounded structure with synthesis and storage components. At the top left, glutamine enters the terminal and is converted to glutamate by the enzyme glutaminase, shown as a green oval with the enzyme name in purple text. This represents the rate-limiting step of glutamate synthesis. The synthesized glutamate molecule is displayed with its chemical structure, showing the amino acid structure with carboxyl and amino groups. On the right side, two synaptic vesicles contain glutamate molecules (blue circles). An arrow indicates glutamate loading into vesicles via the vesicular glutamate transporter (VGLUT), labeled on the right. This demonstrates how glutamate, the primary excitatory neurotransmitter, is synthesized from glutamine in the terminal and stored in vesicles for release.

Figure 10.4

This figure depicts GABA synthesis and storage in a presynaptic terminal. The terminal shows the synthesis pathway starting with glutamate at the top left. Glutamate is converted to GABA by glutamic acid decarboxylase (GAD), shown as a green oval with the enzyme name in purple text. This enzyme catalyzes the rate-limiting step in GABA synthesis. The synthesized GABA molecule is shown below with its chemical structure, displaying the characteristic amino acid structure with a shorter carbon chain than glutamate. On the right, two synaptic vesicles contain GABA molecules (blue circles). An arrow indicates GABA loading into vesicles via the vesicular inhibitory amino acid transporter (VIAAT), labeled on the right. This illustrates how GABA, the primary inhibitory neurotransmitter in the brain, is synthesized from glutamate and stored for release.

Figure 10.5

This figure shows glycine synthesis and storage in a presynaptic terminal. The terminal structure displays the synthesis pathway beginning with serine at the top left. Serine is converted to glycine by serine hydroxymethyltransferase, shown as a green oval with the enzyme name labeled. The synthesized glycine molecule is shown below with its simple amino acid structure, the smallest of the amino acid neurotransmitters. On the right side, two synaptic vesicles contain glycine molecules (blue circles). An arrow indicates glycine loading into vesicles via the vesicular inhibitory amino acid transporter (VIAAT), the same transporter used by GABA. This demonstrates how glycine, another inhibitory neurotransmitter, is synthesized from serine and stored in vesicles. Glycine is more common as a neurotransmitter in the spinal cord than in the brain.

Figure 10.6

This figure illustrates the two-step synthesis pathway and storage of dopamine in a presynaptic terminal. At the top left, tyrosine enters the terminal and is converted to DOPA (dihydroxyphenylalanine) by tyrosine hydroxylase, shown as a green oval with the enzyme name in purple text. This is the rate-limiting step for all catecholamine synthesis. DOPA is then converted to dopamine by DOPA decarboxylase, shown as a second green oval. The dopamine molecule is displayed with its chemical structure, showing the catechol ring with two hydroxyl groups and an ethylamine side chain. On the right, two synaptic vesicles contain dopamine molecules (blue circles). An arrow indicates dopamine loading into vesicles via the vesicular monoamine transporter (VMAT). This demonstrates the complete synthesis pathway for dopamine, a catecholamine involved in reward and movement.

Figure 10.7

This figure shows norepinephrine synthesis occurring within synaptic vesicles, a unique feature among small molecule neurotransmitters. The diagram shows dopamine (blue circles) being packaged into a synaptic vesicle. Inside the vesicle, dopamine beta-hydroxylase (shown as a green oval embedded in the vesicle membrane) converts dopamine into norepinephrine. The norepinephrine molecules (also blue circles) are shown within three vesicles on the right. The norepinephrine chemical structure is displayed below, showing the catechol ring with an additional hydroxyl group on the side chain compared to dopamine. This illustrates the unusual synthesis location for norepinephrine—unlike other small molecule neurotransmitters synthesized in the cytoplasm, norepinephrine is synthesized inside vesicles after dopamine packaging. The enzyme is membrane-bound within the vesicle.

Figure 10.8

This figure illustrates epinephrine synthesis, which requires norepinephrine to exit vesicles for cytoplasmic conversion. At the top left, a vesicle releases norepinephrine (blue circle) into the cytoplasm. The enzyme phenylethanolamine-N-methyltransferase, shown as a green oval, converts norepinephrine into epinephrine in the cytoplasm. The epinephrine molecule is displayed with its chemical structure, showing the additional methyl group on the amino group compared to norepinephrine. On the right, three synaptic vesicles contain epinephrine molecules (blue circles). An arrow indicates epinephrine repackaging into vesicles via the vesicular monoamine transporter (VMAT). This demonstrates the unusual synthesis pathway where norepinephrine must exit vesicles, be converted to epinephrine in the cytoplasm, then be repackaged for storage. Epinephrine functions primarily as a hormone and is used as a neurotransmitter in only limited neurons.

Figure 10.9

This figure depicts the two-step synthesis pathway and storage of serotonin in a presynaptic terminal. At the top left, tryptophan enters the terminal and is converted to 5-hydroxytryptophan by tryptophan hydroxylase, shown as a green oval with the enzyme name in purple text. This is the rate-limiting step in serotonin synthesis. The intermediate 5-hydroxytryptophan is then converted to serotonin by aromatic L-amino acid decarboxylase, shown as a second green oval. The serotonin molecule is displayed with its characteristic indole ring structure containing a hydroxyl group. On the right, two synaptic vesicles contain serotonin molecules (blue circles). An arrow indicates serotonin loading into vesicles via the vesicular monoamine transporter (VMAT). This demonstrates the complete synthesis pathway for serotonin, a biogenic amine neurotransmitter known for its role in mood regulation.

Figure 10.10

This figure shows histamine synthesis and storage in a presynaptic terminal. The terminal depicts a simple synthesis pathway with histidine entering at the top left. Histidine is converted to histamine by histidine decarboxylase, shown as a green oval with the enzyme name in purple text. This single-step reaction is the rate-limiting step in histamine synthesis. The histamine molecule is displayed with its imidazole ring structure characteristic of this biogenic amine. On the right, two synaptic vesicles contain histamine molecules (blue circles). An arrow indicates histamine loading into vesicles via the vesicular monoamine transporter (VMAT), the same transporter used by dopamine, norepinephrine, epinephrine, and serotonin. This illustrates the straightforward synthesis pathway for histamine, a biogenic amine neurotransmitter with various functions in the nervous system.

Figure 10.11

This figure illustrates neuropeptide synthesis in the cell body and transport to the terminal, contrasting with small molecule neurotransmitter synthesis. On the left, a neuron shows the nucleus (blue sphere with nuclear envelope), rough endoplasmic reticulum (studded with ribosomes), and Golgi apparatus (stacked tan membranes). Three boxes on the right show the synthesis stages. The top box shows a chromosome with a gene containing a promoter (gray) and three exons (green). The middle box shows the prepropeptide, a colored bar representing the initial translation product with signal sequence (orange), peptide sequences (purple), and spacer regions (yellow). The bottom box shows processing: the propeptide (purple and yellow segments) after signal sequence removal, and the final peptides (purple segments) packaged into vesicles after cleavage. This demonstrates how neuropeptides require synthesis in the soma and transport to terminals, unlike small molecule neurotransmitters synthesized locally in terminals.

Figure 10.12

This figure shows bidirectional transport mechanisms in neurons. A neuron is depicted with its cell body on the left containing dendrites and nucleus, a myelinated axon extending to the right (shown as gray oval segments), and an axon terminal with branching endpoints on the right. Two arrows indicate transport directions along the axon. The top arrow points left, labeled “Retrograde transport,” indicating movement from the terminal back toward the cell body. The bottom arrow points right, labeled “Anterograde transport,” indicating movement from the cell body toward the terminal. This illustrates how cellular components move throughout the neuron: anterograde transport delivers newly synthesized materials (including neuropeptide-containing vesicles) from the soma to terminals, while retrograde transport returns materials from terminals to the soma for degradation or recycling. These transport mechanisms are essential for neuronal function and maintenance.

Chapter 11 – Neurotransmitter Release

Animation 11.1

The animation illustrates the propagation of an electrical action potential down a myelinated neuron. The on-screen layout features a complete neuron with branching dendrites, a central cell body, and a long axon extending to the right that is covered in discrete, gray-colored myelin insulation segments. The specialized junction connecting the cell body to the axon is highlighted in green and labeled as the axon hillock. To the right of the cell body, an inset panel displays a static graph plotting membrane potential in millivolts over time, showing a sharp upward electrical spike that peaks well above 0 mV from a resting baseline of -65 mV. Text next to the graph defines an action potential as a brief change in the electrical potential across the membrane that leaves the inside of the neuron positively charged. As the animation plays, a vertical black line acting as an electrical signal indicator originates at the green axon hillock and moves smoothly and continuously from left to right along the gaps between the myelin segments. The signal trace travels down the length of the axonal shaft, demonstrating how the electrical impulse propagates sequentially past each insulated segment toward the downstream terminal branches.

Animation 11.2

The animation tracks the arrival of an action potential and the subsequent ionic currents within a presynaptic terminal. The visual layout displays a bulbous, curved presynaptic terminal structure containing five circular synaptic vesicles filled with blue dots. Embedded along the left boundary of the terminal membrane are blue channels, while the right border contains four closed purple channels. A black action potential wave indicator flashes on the left, causing blue sodium spheres to cross into the terminal through the blue channels. As this inward sodium current spreads across the terminal, bright yellow lightning bolt icons flash next to the purple channels on the right to represent voltage changes. In response to this depolarization, the purple voltage-gated channels open wide, and numerous purple spheres labeled as calcium immediately rush inward from the extracellular environment into the terminal cytoplasm.

Figure 11.1

This figure shows vesicle organization in a presynaptic terminal. The terminal is depicted as a rounded structure with the plasma membrane (shown as a purple bilayer with embedded proteins). Voltage-gated sodium channels (blue with dotted pattern) and voltage-gated calcium channels (purple with striped pattern) are embedded in the membrane. The right side shows active zones, specialized regions where vesicles dock for rapid release. Four small molecule neurotransmitter vesicles (circles with blue dots) are docked at active zones via purple SNARE protein complexes. In the center, five vesicles containing small molecule neurotransmitters form the reserve pool, ready to move into empty active zones. Two vesicles containing neuropeptides (purple rectangles) are shown on the left, located away from active zones and membrane, indicating slower release kinetics. This spatial organization reflects functional differences between small molecule and peptide neurotransmitter release mechanisms.

Figure 11.2

This figure illustrates vesicle docking through SNARE protein interactions. A cross-section shows a synaptic vesicle (purple bilayer membrane) containing five small molecule neurotransmitter molecules (blue circles) positioned above the presynaptic terminal membrane. The vesicle membrane contains synaptobrevin (shown as a black helical protein), the v-SNARE protein. The terminal membrane below contains two t-SNARE proteins: SNAP-25 (shown as a green helical protein) and syntaxin (shown as a black helical protein with transmembrane domain). These three SNARE proteins interact and intertwine, forming a complex that bridges the vesicle and terminal membranes. On either side of the docking site, multiple voltage-gated calcium channels (purple with striped pattern) are embedded in the terminal membrane. A voltage-gated calcium channel is also shown on the far right. The SNARE protein complex brings vesicles into close proximity with the membrane, positioning them for rapid calcium-triggered fusion.

Animation 11.3

The animation focuses on the molecular interactions occurring at a docked synaptic vesicle before exocytosis. A large circular synaptic vesicle filled with blue neurotransmitter spheres sits tightly against a horizontal presynaptic plasma membrane. Intertwined below the vesicle are coiled snare proteins labeled as synaptobrevin, SNAP-25, and syntaxin. Extending outward from both sides of the vesicle membrane are two straight, black, pin-like sensor proteins labeled as synaptotagmin. On the lower right, a yellow lightning bolt icon flashes next to an open purple channel. A purple calcium sphere passes through the channel and enters the intracellular space. Immediately afterward, two additional purple calcium spheres appear on the left and right sides of the vesicle, migrating directly toward the black synaptotagmin proteins. The purple spheres latch securely onto the ends of the black synaptotagmin pins, visually demonstrating the conformational calcium-binding step.

Animation 11.4

The animation illustrates the final structural mechanics of vesicle fusion and neurotransmitter exocytosis. The molecular layout features a circular synaptic vesicle containing five blue neurotransmitter spheres, docked tightly above a horizontal plasma membrane via coiled snare protein complexes. Two purple calcium spheres are already bound to the ends of the black synaptotagmin sensor pins. As the sequence plays, the bound synaptotagmin complex shifts, driving the coiled snare proteins to tightly twist and pull together. This physical tension causes the lower lipid boundary of the circular vesicle and the upper boundary of the plasma membrane to merge. The fused membranes pull apart horizontally down the middle, creating an open gateway or fusion pore. With the structural barrier gone, the blue neurotransmitter spheres spill out sequentially from the inside of the vesicle through the open pore, passing downward into the extracellular space.

Figure 11.3

The diagram illustrates the anatomical components of a typical chemical synapse, showing a distinct separation between a presynaptic terminal on the left and a postsynaptic membrane on the right. The presynaptic terminal is a large, rounded axonal ending that contains numerous small, circular structures representing synaptic vesicles filled with chemical neurotransmitter molecules. Separating the presynaptic terminal from the target cell is a clear, narrow horizontal gap labeled as the synaptic cleft, highlighting that the two neurons share no direct physical or cytoplasmic connection. Directly across the cleft, the postsynaptic membrane is lined with specialized, embedded protein complexes representing neurotransmitter receptors. This layout visually emphasizes the unidirectional nature of chemical transmission, where signals must be converted from electrical activity into chemical messengers to cross the structural divide.

Chapter 12 – Neurotransmitter Action: Ionotropic Receptors

Figure 12.1

This figure shows the distribution of receptors on a neuron. The neuron displays typical morphology with branching dendrites at the top, a cell body (soma) containing a nucleus on the left, and a myelinated axon (shown as gray segments) extending from the soma to the axon terminal on the right. Red arrows point to multiple locations along the dendrites and cell body, indicating where receptors are primarily located. Three arrows point to distal dendrites, one points to a proximal dendrite near the soma, and two arrows point to different regions of the cell body. These locations represent where the neuron receives incoming synaptic information from other neurons. The axon and terminal lack arrows, indicating that receptors are not typically present in these regions. This distribution pattern reflects the function of receptors in receiving and integrating synaptic inputs.

Animation 12.1

A side-by-side comparison displays two different gating mechanisms across a horizontal lipid bilayer membrane. On the left side, labeled “Ligand-gated channels,” a teal channel with a checkered pattern and a solid yellow channel are embedded in the membrane, while a separate blue dotted channel sits on the right side under the heading “Voltage-gated channels.” Two distinct molecular keys—a teal star labeled “Glutamate” and an orange cross labeled “GABA”—hover in the extracellular space above the ligand-gated receptors. As the sequence plays, the glutamate star attaches directly to the teal channel, causing its pore to open wide and a blue sphere labeled as sodium to flow down through it into the cell. Concurrently, the GABA cross binds to the yellow channel, opening its pore to let a yellow sphere labeled as chloride pass into the cell. On the right side, a sharp orange lightning bolt icon strikes beneath the closed blue voltage-gated channel, representing a localized voltage shift. This electrical stimulation triggers the blue channel to open its gates, allowing an extracellular blue sodium sphere to pass through into the cell interior.

Animation 12.2

The animation shows the selective nature of ligand-receptor interactions across a stretch of a postsynaptic lipid membrane. Alternating teal checkered channels and solid yellow channels are embedded side by side along the bilayer surface. Multiple teal star-shaped molecules labeled as glutamate drift randomly within the extracellular fluid above the membrane. As they move, three of the glutamate stars align perfectly with and lock into corresponding binding pockets situated exclusively on the extracellular surfaces of the teal checkered channels. None of the glutamate stars approach or bind to the adjacent yellow channels, demonstrating structural specificity.

Animation 12.3

A horizontal cell membrane features two distinct ionotropic glutamate receptors, labeled “AMPA” on the left and “Kainate” on the right. Initially, blue sodium spheres populate the upper extracellular space, while green potassium spheres sit in the lower intracellular space. A teal star representing glutamate binds to each receptor simultaneously. Upon binding, both the AMPA and kainate channels shift into their open states. Within each channel pore, a green potassium sphere moves upward to exit the cell while a blue sodium sphere moves downward to enter the cell at the exact same time. Following this initial bidirectional crossover, multiple blue sodium spheres continue to flow rapidly down through both channels into the intracellular solution, illustrating a dominant inward positive current.

Animation 12.4

The animation illustrates the conditional gating of an NMDA receptor alongside an AMPA receptor. A horizontal membrane separates an extracellular space containing blue sodium spheres from an intracellular space containing green potassium spheres. An AMPA receptor is situated on the left, and an NMDA receptor containing a purple sphere labeled as magnesium lodged tightly inside its pore is on the right. An inset graph on the far right monitors the membrane potential, starting below a marker labeled 60 mV. When glutamate stars bind to both receptors, the AMPA channel opens immediately, letting blue sodium spheres rush inward, which causes the line on the voltage graph to rise up past -60 mV. Despite glutamate being bound to the NMDA receptor, its pore remains plugged by the purple magnesium sphere until this voltage rise occurs. Once the graph records the depolarization, a bright orange lightning bolt flashes beneath the open NMDA receptor. Simultaneously, the purple magnesium sphere is repelled upward out of the channel pore into the extracellular space . With the block cleared, a green potassium sphere moves upward out of the cell, while blue sodium spheres and purple spheres labeled as calcium pass downward into the intracellular space through the open NMDA channel.

Animation 12.5

A horizontal cell membrane contains a solid yellow receptor on the left and a yellow dotted receptor on the right. Yellow spheres labeled as chloride are scattered throughout the upper extracellular space. An orange cross representing GABA approaches the solid yellow channel on the left, while an orange teardrop representing glycine approaches the dotted yellow channel on the right. As both ligands dock onto their respective receptors, the internal pores of both channels open wide. Multiple yellow chloride spheres immediately stream downward from the extracellular side, traveling through both open pathways to collect in the intracellular space below the membrane.

Animation 12.6

A blue dotted channel sits within a horizontal lipid membrane with blue sodium spheres hovering in the extracellular fluid above it. A real-time graph at the bottom right tracks the membrane potential, starting from a baseline at –60 mV. An orange lightning bolt icon strikes next to the channel, signaling an opening event. As the channel opens, blue sodium spheres flow downward through the pore into the intracellular space. The graph registers this inward positive current as a steady, upward tracer line that climbs continuously from –60 mV toward the top of the vertical axis, demonstrating depolarization toward the sodium equilibrium potential.

Animation 12.7

A solid yellow GABA receptor is embedded in a horizontal membrane, with yellow chloride spheres situated on both sides. Text on the bottom left states that the chloride equilibrium potential and the GABA receptor reversal potential are both –65 mV. A voltage graph at the bottom right has its baseline set near –65 mV. When an orange GABA cross docks onto the extracellular surface of the receptor, the channel opens, and a single yellow chloride ion moves downward into the cell while another yellow chloride ion simultaneously moves upward out of the cell. This equal bidirectional exchange results in no net movement of charge, and the tracer line on the graph remains flat, showing no change from the resting potential.

Animation 12.8

A teal checkered glutamate receptor and a closed yellow channel are embedded in a horizontal lipid membrane. Blue sodium spheres sit above the membrane, and green potassium spheres sit below it. On the graph at the bottom right, the membrane potential tracer line begins at a highly negative position below –60 mV. When a glutamate star binds to the teal receptor, it opens, and a green potassium sphere moves upward out of the cell while a blue sodium sphere moves downward into the cell. Because of the hyperpolarized starting potential, multiple blue sodium spheres rush downward into the intracellular space in rapid succession, creating a substantial inward current. The line on the graph reacts by rising steeply toward 0 mV.

Animation 12.9

A teal checkered glutamate receptor is embedded within a horizontal lipid membrane with blue sodium spheres located above and green potassium spheres located below. The reference graph at the bottom right shows the membrane potential held steady at 0 mV. A teal glutamate star remains bound to the open receptor. As the animation runs, blue sodium spheres pass downward through the channel pore into the cell, while green potassium spheres pass upward through the same channel out of the cell at an identical, alternating rate. The tracer line on the graph remains flat and steady at 0 mV, demonstrating that net current flow is zero at the receptor’s reversal potential.

Chapter 13 – Neurotransmitter Action: G-Protein-Coupled Receptors

Figure 13.1

This figure shows the distribution of receptors on a neuron. The neuron displays typical morphology with branching dendrites at the top, a cell body (soma) containing a nucleus on the left, and a myelinated axon (shown as gray segments) extending from the soma to the axon terminal on the right. Red arrows point to multiple locations along the dendrites and cell body, indicating where receptors are primarily located. Three arrows point to distal dendrites, one points to a proximal dendrite near the soma, and two arrows point to different regions of the cell body. These locations represent where the neuron receives incoming synaptic information from other neurons. The axon and terminal lack arrows, indicating that receptors are not typically present in these regions. This distribution pattern reflects the function of receptors in receiving and integrating synaptic inputs.

Figure 13.2

This figure shows the inactive G-protein complex structure near the cell membrane. The membrane is depicted as a purple phospholipid bilayer at the top. Below the membrane, the G-protein complex consists of three distinct subunits. The alpha subunit (Gα) is shown as a large light blue oval. Adjacent to the alpha subunit are the beta (β) and gamma (γ) subunits, depicted as a dark blue circle with a tail-like extension representing the gamma subunit. A small dark green oval labeled GDP is positioned next to the alpha subunit, indicating the GDP molecule bound to the alpha subunit in the resting state. This inactive configuration awaits activation by a G-protein-coupled receptor. When a neurotransmitter binds to a GPCR, the receptor interacts with this complex, triggering GDP-to-GTP exchange and subsequent G-protein activation.

Animation 13.1

The animation illustrates the molecular activation of a G-protein complex . A purple G-protein-coupled receptor spans a cell membrane. On the intracellular side, an inactive G-protein complex consisting of an alpha subunit carrying a GDP molecule sits bound to a beta-gamma subunit complex. When a neurotransmitter ligand docks onto the extracellular surface of the purple receptor, it triggers a shape change that causes the alpha subunit to eject its GDP molecule and pick up a high-energy GTP molecule instead, activating the G-protein complex.

Animation 13.2

The animation details the dissociation and spreading of an activated G-protein complex along a membrane boundary. Following the binding of a high-energy GTP molecule, the activated G-protein complex physically splits apart into two separate signaling components: the alpha-GTP subunit and the beta-gamma subunit complex. Both individual units immediately drift away from the central purple receptor, diffusing horizontally along the inner surface of the lipid bilayer to approach separate, distant target effector proteins embedded elsewhere in the membrane.

Animation 13.3

The animation demonstrates direct, shortcut gating of an ion channel by a G-protein subunit. An acetylcholine molecule binds to a muscarinic receptor in a membrane, causing its attached G-protein complex to activate and separate. The freed beta-gamma subunit drifts horizontally along the inner surface of the membrane until it collides with and binds directly onto a nearby green potassium channel. This binding causes the green channel to open its pore, allowing green potassium spheres to stream rapidly out of the cell interior to hyperpolarize the membrane.

Figure 13.3

This figure illustrates how different alpha subunits initiate distinct signaling pathways using norepinephrine as an example. The figure has three panels (A, B, C), each showing two stages: receptor-G-protein coupling (left) and effector protein modulation (right). Panel A shows the Gs alpha subunit pathway. The beta-adrenergic receptor (purple) with bound norepinephrine (N) couples to Gs, which activates adenylyl cyclase (brown enzyme). The activated enzyme (shown with yellow glow) initiates cellular effects. Panel B shows the Gi alpha subunit pathway. The alpha-2 adrenergic receptor (pink dotted) couples to Gi, which inhibits adenylyl cyclase. The inhibited enzyme (shown with red block) prevents cellular effects. Panel C shows the Gq alpha subunit pathway. The alpha-1 adrenergic receptor (gray) couples to Gq, which activates phospholipase C (brown enzyme). This demonstrates how one neurotransmitter produces diverse cellular effects depending on which receptor subtype and G-protein alpha subunit are present.

Animation 13.4

The animation maps out the steps of the cyclic AMP second messenger cascade . An activated G-protein alpha subunit moves horizontally along the membrane to bind with and turn on an adenylyl cyclase enzyme. Once turned on, the adenylyl cyclase begins rapidly converting cytoplasmic ATP molecules into multiple smaller cyclic AMP (cAMP) molecules. These newly formed cAMP messengers diffuse deeper into the cytoplasm, where they bind to regulatory sections of inactive protein kinase A (PKA) protein clusters, triggering the release of active PKA catalytic subunits that can now phosphorylate other proteins.

Animation 13.5

The animation shows two distinct ways that the adenylyl cyclase pathway regulates membrane permeability. On the left, newly created cyclic AMP (cAMP) molecules diffuse directly to a closed channel, binding onto it to open its pore and let blue sodium spheres pass into the cell. On the right, an activated protein kinase A (PKA) subunit approaches a closed channel, delivering a phosphate group from an ATP molecule directly onto the channel protein to alter its structural gating properties and allow purple calcium spheres to flow into the cell.

Animation 13.6

The animation illustrates the broad cytoplasmic and nuclear reach of an activated kinase cascade. Activated protein kinase A (PKA) subunits separate and diffuse outward through the intracellular space. One PKA unit interacts with nearby cytoplasmic target proteins to alter rapid processes like neurotransmitter handling. Concurrently, an adjacent PKA unit travels directly through a nuclear pore to enter the cell nucleus, where it attaches a phosphate group onto a CREB transcription factor protein bound to a strand of DNA to switch on gene expression for long-term structural changes.

Animation 13.7

The animation illustrates the lipid cleavage signaling cascade initiated by Gq-coupled receptors . An activated alpha subunit turns on a membrane-bound phospholipase C enzyme, which immediately cuts a membrane lipid into two distinct secondary messengers: a DAG molecule that stays inside the lipid bilayer and an IP3 molecule that detaches into the cytoplasm. The DAG molecule moves sideways to activate protein kinase C (PKC) at the membrane boundary. Simultaneously, the free IP3 molecule travels to the endoplasmic reticulum, binding to and opening calcium channels to release a flood of calcium ions into the cell interior.

Figure 13.4

This figure demonstrates signal amplification in GPCR signaling through three sequential panels. Panel A shows one GPCR (purple receptor with bound transmitter T) activating multiple G-protein complexes. Three activated Gα subunits (light blue with GTP) are shown, each separated from their beta-gamma components. Panel B illustrates effector protein amplification. Three activated Gα subunits (shown with yellow glow) each interact with adenylyl cyclase enzymes (brown). Each activated enzyme produces multiple cAMP molecules (shown as small triangles spreading downward), demonstrating how one G-protein activates an enzyme that creates many second messengers. Six sets of PKA enzymes (green ovals) are shown being activated. Panel C depicts kinase amplification. Multiple PKA molecules phosphorylate diverse cellular proteins (shown as various colored shapes—red, purple, orange, and blue) marked with P for phosphorylation. This cascade shows how one neurotransmitter-receptor interaction produces widespread cellular effects through amplification at each stage.

Chapter 14 – Neurotransmitter Clearance

Figure 14.1

This figure illustrates acetylcholine clearance from the synaptic cleft through enzymatic degradation. The presynaptic terminal on the left contains three synaptic vesicles with acetylcholine molecules (blue circles). Multiple acetylcholine molecules are dispersed in the synaptic cleft. Acetylcholinesterase, an enzyme represented by a black symbol in the center of the cleft, cleaves acetylcholine into two products: choline and acetate. Arrows from the enzyme point to these breakdown products labeled in the upper portion of the cleft. A choline transporter in the presynaptic membrane (shown as a gray transporter protein) moves choline back into the terminal for acetylcholine resynthesis. The acetylcholine chemical structure is shown in the lower portion of the cleft. On the right, the postsynaptic membrane displays acetylcholine receptors (orange). This demonstrates the unique clearance mechanism for acetylcholine—enzymatic degradation occurs in the synaptic cleft rather than after reuptake, with choline recycling enabling efficient neurotransmitter synthesis.

Figure 14.2

This figure shows glutamate clearance through dual transport mechanisms involving both neurons and glial cells. The presynaptic terminal on the left contains vesicles with glutamate molecules (blue circles). Glutamate molecules are dispersed in the synaptic cleft. Excitatory amino acid transporters (shown as yellow transporters) are present in both the presynaptic membrane and in a nearby glial cell membrane. These transporters use sodium co-transport, coupling sodium influx to glutamate uptake. Arrows indicate glutamate can be transported in two directions: back into the presynaptic terminal where it is repackaged into vesicles, or into glial cells. Within glial cells, glutamine synthetase (shown as a gray enzyme symbol) converts glutamate into glutamine. Glutamine is then transported out of the glial cell and back to the presynaptic terminal for reconversion to glutamate. The glutamate chemical structure appears in the cleft. The postsynaptic membrane on the right shows glutamate receptors. This glutamate-glutamine cycle between neurons and glia ensures efficient neurotransmitter recycling while preventing excitotoxicity.

Figure 14.3

This figure depicts parallel clearance mechanisms for GABA and glycine through two side-by-side panels. The left panel shows GABA clearance. The presynaptic terminal contains vesicles with GABA molecules (blue circles). GABA transporters (gray symbols) in both the presynaptic membrane and glial cell membrane use sodium co-transport to move GABA from the cleft. Arrows indicate GABA can be transported back into the presynaptic terminal for repackaging into vesicles, or into glial cells where enzymatic breakdown occurs (indicated by “GABA breakdown” label). The right panel mirrors this organization for glycine. Glycine transporters move glycine molecules into either the presynaptic terminal for vesicular repackaging or into glial cells for enzymatic degradation (indicated by “Glycine breakdown” label). The GABA and glycine chemical structures are shown in their respective cleft regions. Both panels show postsynaptic membranes with receptors. This demonstrates that inhibitory amino acid neurotransmitters share similar dual-pathway clearance mechanisms through neuronal and glial transporters.

Figure 14.4

This figure illustrates dopamine clearance through reuptake and subsequent metabolism or storage. The presynaptic terminal contains vesicles with dopamine molecules (blue circles). Dopamine molecules in the synaptic cleft are transported back into the terminal via the dopamine transporter (DAT), shown as a gray transporter protein in the presynaptic membrane. Once inside the terminal, dopamine faces two fates indicated by labeled enzymes: monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), both shown as gray symbols with arrows, degrade dopamine into inactive metabolites. Alternatively, dopamine can be repackaged into synaptic vesicles for future release, shown by vesicles containing dopamine. The dopamine chemical structure with its catechol ring is displayed in the cleft. The postsynaptic membrane on the right shows dopamine receptors. This demonstrates that monoamine clearance occurs through presynaptic reuptake followed by either metabolic breakdown or vesicular recycling, allowing regulation of synaptic dopamine levels.

Figure 14.5

This figure shows norepinephrine clearance through mechanisms identical to dopamine. The presynaptic terminal contains vesicles with norepinephrine molecules (blue circles). The norepinephrine transporter (NET), shown as a gray transporter protein in the presynaptic membrane, moves norepinephrine from the synaptic cleft back into the terminal. Inside the terminal, two pathways are indicated: MAO and COMT enzymes (shown as gray symbols with arrows) degrade norepinephrine into inactive metabolites, or norepinephrine is repackaged into synaptic vesicles. The norepinephrine chemical structure showing the catechol ring with an additional hydroxyl group on the side chain (compared to dopamine) is displayed in the cleft. The postsynaptic membrane shows norepinephrine receptors. This illustrates that norepinephrine, as a catecholamine like dopamine, shares the same clearance strategy: transporter-mediated reuptake followed by either enzymatic degradation or vesicular storage, maintaining precise control over noradrenergic signaling.

Figure 14.6

This figure depicts serotonin clearance through reuptake and metabolism. The presynaptic terminal contains vesicles with serotonin molecules (blue circles). The serotonin transporter (SERT), shown as a gray transporter protein in the presynaptic membrane, moves serotonin from the synaptic cleft back into the terminal. Inside the terminal, serotonin faces two possible fates: MAO (monoamine oxidase, shown as a gray enzyme symbol with an arrow) degrades serotonin into inactive metabolites—notably, COMT is absent for serotonin unlike the catecholamines. Alternatively, serotonin is repackaged into synaptic vesicles. The serotonin chemical structure displaying the indole ring is shown in the cleft. The postsynaptic membrane shows serotonin receptors. This demonstrates that serotonin, while following the general monoamine clearance pattern of reuptake and subsequent degradation or storage, differs from catecholamines by using only MAO (not COMT) for enzymatic breakdown, reflecting its distinct indole structure versus the catechol structure.

Chapter 15 – Drug and Toxin Effects

Figure 15.1

This figure compares normal neurotransmitter synthesis and packaging with drug-altered processes through two side-by-side panels. The left panel labeled “Control” shows normal function. Precursor molecules (teal pentagons) are converted by an enzyme (green oval) into neurotransmitter molecules (blue circles) through synthesis. Below, vesicular transporters (gray symbols) package neurotransmitters into synaptic vesicles, which contain multiple neurotransmitter molecules ready for release. The right panel labeled “Drug treatment” shows two drug effects. At the top, L-DOPA (multiple teal pentagons) serves as an excess dopamine precursor, increasing the enzyme’s substrate availability and producing more dopamine molecules in the cytoplasm. At the bottom, reserpine (shown as a gray blocker symbol with yellow accent) blocks the vesicular transporter. This blockade prevents neurotransmitters from being packaged into vesicles, resulting in vesicles with few or no neurotransmitter molecules. This demonstrates how drugs can alter neurotransmitter availability by modifying synthesis or storage mechanisms.

Figure 15.2

This figure illustrates three types of drug actions at postsynaptic receptors through four panels. The first panel labeled “Control Ex: GABA” shows normal function where a GABA neurotransmitter (light blue circle) binds to a receptor (orange channel) in the postsynaptic membrane, producing an IPSP. The second panel labeled “Agonist Ex: Muscimol” shows muscimol (dark blue circle) binding to and activating the GABA receptor, mimicking GABA’s effect and producing an IPSP. The third panel labeled “Antagonist Ex: Bicuculine” shows bicuculine (orange pac-man shape) blocking the receptor binding site. GABA cannot bind, preventing receptor activation and producing no IPSP. The fourth panel labeled “Receptor modulator Ex: Alcohol” shows alcohol (green triangle) binding to a modulatory site on the receptor. When GABA also binds, the receptor response is enhanced, producing a stronger IPSP than normal. This demonstrates the three main mechanisms by which drugs modify receptor function: mimicking neurotransmitters (agonists), blocking neurotransmitters (antagonists), or altering receptor sensitivity (modulators).

Figure 15.3

This figure contrasts normal neurotransmitter clearance with drug-blocked clearance through two panels. The left panel shows normal clearance mechanisms. Reuptake transporters (gray symbols) in the presynaptic membrane move neurotransmitter molecules (blue circles) from the synaptic cleft back into the terminal. Inside the terminal, degradation enzymes (shown as gray arrows) break down neurotransmitters. In the synaptic cleft, additional degradation enzymes (gray symbol) metabolize neurotransmitters. The right panel shows three drug blockade examples. Cocaine (shown as a purple blocker with pink accent) blocks the dopamine transporter, preventing reuptake and causing neurotransmitter accumulation in the cleft. MAOIs (monoamine oxidase inhibitors, shown as a red blocker) block intracellular MAO enzymes, preventing neurotransmitter degradation within the terminal. Organophosphates (shown as a red blocker) inhibit acetylcholinesterase in the synaptic cleft, preventing extracellular degradation. All three mechanisms result in increased neurotransmitter concentration and prolonged signaling in the synaptic cleft.

Chapter 16 – Epigenetics

Figure 16.1

This figure illustrates the central dogma of molecular biology through three stages. At the top, double-stranded DNA is shown as a twisted double helix with complementary base pairs: cytosine (purple, labeled C) pairs with guanine (green, labeled G), and adenosine (blue, labeled A) pairs with thymine (orange, labeled T). A black arrow labeled “Transcription (Nucleus)” points downward to the middle section showing single-stranded mRNA. The mRNA strand displays colored nucleotide bases in sequence: A-U-G-A-C-C-A-G-G-A-A-G-C-A-G-U, where uracil (brown, labeled U) replaces thymine. A key on the right identifies all five nucleotides with their colors. Another black arrow labeled “Translation (Ribosome)” points downward to the bottom section showing a protein chain of five amino acids represented as connected teal circles labeled Met-Thr-Arg-Lys-Gln. This demonstrates how genetic information flows from DNA through RNA to produce functional proteins, with each step occurring in specific cellular locations.

Figure 16.2

This figure shows the molecular machinery of transcription. A segment of double-stranded DNA is partially unwound, exposing the nucleotide bases in the middle section. Three transcription factors (shown as colored circles—green, purple, and blue) bind to the DNA along with RNA polymerase (shown as a light blue rounded rectangle). These proteins form a transcription complex that reads the DNA template strand. An mRNA strand (shown on the left) extends from the transcription complex, displaying the sequence A-U… being synthesized. The DNA base pairs are visible within the transcription bubble, showing the template strand being read in the 3′ to 5′ direction to synthesize mRNA in the 5′ to 3′ direction. The figure demonstrates how RNA polymerase uses DNA as a template to create a complementary mRNA sequence through base pairing rules. A key identifies transcription factors and RNA polymerase. This process occurs in the nucleus and is the first step in gene expression.

Figure 16.3

This figure illustrates the hierarchical organization of DNA from its basic double helix structure to the condensed chromosome through five progressive stages. Starting from the left, naked double-stranded DNA is shown as the familiar twisted ladder structure. The DNA then wraps around histone proteins (shown as tan disc-shaped octamers) forming “beads on a string,” with DNA making approximately 1.7 turns around each histone core. These histone-DNA complexes are nucleosomes. Multiple nucleosomes compact together into a fiber structure forming chromatin, which appears as a looser, coiled arrangement. The chromatin then condenses further into a more tightly coiled structure with additional folding. Finally, maximum condensation produces the characteristic X-shaped chromosome visible during cell division, shown as two densely packed sister chromatids. This packaging reduces DNA length by approximately 10,000-fold, allowing roughly two meters of DNA to fit into a nucleus only micrometers in diameter while still permitting regulated access for transcription.

Figure 16.4

This figure contrasts two chromatin states determining transcriptional accessibility. The left side shows tightly wound, transcriptionally inactive chromatin where DNA (shown with colored nucleotide bases) is wrapped tightly around four histone octamers (tan discs). The compact structure prevents transcription factors and RNA polymerase from accessing the DNA. An arrow points from the histones to unbound transcription factors and RNA polymerase (light blue rectangle), illustrating that these proteins cannot bind. The label “RNA polymerase cannot bind; no gene transcription” emphasizes gene silencing. The right side shows loosely wound, transcriptionally active chromatin where nucleosomes have separated, unwinding the DNA. Here, transcription factors (green, purple, blue circles) and RNA polymerase successfully bind to the accessible DNA, with RNA polymerase positioned between two histone octamers. An mRNA strand extends from the polymerase, indicating active transcription. Bidirectional arrows labeled “Unwind” and “Re-wind” connect the two states, showing this is a reversible, regulated process controlling gene expression.

Figure 16.5

This figure illustrates how DNA methylation regulates gene accessibility. On the left, methylated DNA is shown with black methyl groups (CH3) attached to the DNA backbone. In the center panel labeled “High methylation, Tightly wound, Inaccessible to polymerase,” four histone octamers (tan discs) are densely packed with DNA tightly wrapped around them, and numerous methyl groups are visible on the DNA. This compact structure prevents transcription factors and RNA polymerase from binding, as shown by an arrow pointing to unbound proteins below. The label “RNA polymerase cannot bind; no gene transcription” indicates gene silencing. Bidirectional arrows labeled “Demethylation” and “Methylation” connect to the right panel showing “Low methylation, Loosely wound, Accessible to polymerase.” Here, fewer or no methyl groups are present, nucleosomes are separated, and transcription factors (colored circles) and RNA polymerase successfully bind to the accessible DNA. The label “RNA polymerase binds; gene transcription occurs” indicates active transcription. This demonstrates how methylation patterns control gene expression without changing DNA sequence—the molecular basis of epigenetics.

Figure 16.6

This figure depicts transgenerational epigenetic inheritance through a three-generation family pedigree using circles and squares. At the top (grandparent generation), an affected individual (circle) shows methylation markers (four black methyl groups with CH3 symbols) and is labeled with red “Stress” arrows indicating environmental exposure. Their partner (square) shows no methylation. In the second generation (parent generation), all three offspring display methylation patterns: two circles and one square all contain four methyl groups, demonstrating transmission from the affected grandparent. One methylated male pairs with an unmethylated circle. In the third generation (grandchildren), two of four offspring show methylation despite no direct stress exposure: two squares display four methyl groups each, while two circles remain unmethylated. This illustrates that stress-induced methylation in the grandparent can be inherited through both the F1 (children) and F2 (grandchildren) generations, demonstrating transgenerational epigenetic inheritance where environmental effects can influence descendants who were never directly exposed.