Chapter 8 – Synapse Structure

Figure 8.1

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 8.1

This animation demonstrates how ions flow through electrical synapses formed by gap junctions. The animation shows two neurons connected by gap junction proteins called connexons that form channels directly linking the cytoplasm of the presynaptic and postsynaptic cells. At the start, both neurons are at rest with their typical ion distributions. When an action potential propagates down the presynaptic neuron’s axon, voltage-gated sodium channels open, causing sodium influx. The animation shows sodium ions (represented as blue circles with positive charges) flowing into the presynaptic cell through the open voltage-gated sodium channels. Because the gap junctions create direct connections between the two cells, these sodium ions can immediately flow from the presynaptic neuron through the connexon channels into the postsynaptic neuron. This direct ion transfer causes immediate depolarization of the postsynaptic membrane without any delay or need for chemical neurotransmitter release. The postsynaptic neuron’s membrane potential changes rapidly in response to the presynaptic action potential, demonstrating the speed and efficiency of electrical synaptic transmission. The animation emphasizes that the connexon proteins create open pores allowing direct electrical coupling between the connected neurons.

Animation 8.2

This animation illustrates the bidirectional nature of electrical synapses, contrasting with the unidirectional transmission of chemical synapses. The animation shows two neurons connected by gap junction channels formed by connexon proteins. The animation demonstrates that electrical synapses allow ion flow in either direction depending on the electrochemical gradients. First, an action potential in the left neuron (presynaptic in this direction) causes sodium influx, and these ions flow through the gap junctions into the right neuron, depolarizing it. Then the animation reverses the scenario, showing an action potential initiated in the right neuron. Sodium ions entering this neuron can flow backward through the same gap junction channels into the left neuron, causing depolarization in the opposite direction. The gap junctions do not impose any directional restriction on ion movement—ions can travel either way through the open pores. The direction of ion flow is determined solely by the electrochemical gradients, not by the structure of the synapse itself. This bidirectionality is a fundamental difference from chemical synapses, which can only transmit signals in one direction due to the spatial separation of neurotransmitter release machinery (presynaptic) and receptors (postsynaptic).

Animation 8.3

This animation demonstrates that gap junctions in electrical synapses allow passage of small cellular molecules in addition to ions. The animation shows two neurons connected by gap junction channels with a diameter large enough to permit molecules beyond simple ions. The animation depicts small cellular signaling molecules such as ATP (adenosine triphosphate) and second messengers (like cyclic AMP, IP3, or calcium) moving between the connected neurons through the gap junction pores. These molecules are represented as structures slightly larger than individual ions. The animation shows these signaling molecules diffusing from one neuron through the connexon channels into the adjacent neuron, allowing not just electrical coupling but also metabolic and biochemical coupling between cells. This transfer of signaling molecules enables coordinated cellular responses and communication beyond simple electrical signals. The gap junction pores have size selectivity—they are large enough to pass small molecules like ATP and common second messengers but small enough to prevent passage of large proteins or organelles. This molecular exchange through electrical synapses plays important roles in cellular mechanisms and coordinated activity in neural networks, particularly during development.

Figure 8.2

This figure illustrates the structure and function of a chemical synapse through two sequential panels showing neurotransmitter release and receptor binding. Panel A shows the presynaptic terminal on the left containing two synaptic vesicles (depicted as circles containing blue dots representing neurotransmitter molecules). A small action potential waveform appears above the presynaptic terminal. Arrows point from the vesicles toward the synaptic cleft, indicating the direction of neurotransmitter release. The presynaptic membrane is labeled at the bottom of the terminal. On the right side is the postsynaptic membrane with six neurotransmitter receptors (shown as orange/brown structures with vertical slots) embedded in the membrane. The gap between the two membranes represents the synaptic cleft, the space that separates the presynaptic and postsynaptic cells in a chemical synapse. Panel B shows the same synapse after neurotransmitter release. The presynaptic terminal now shows concave indentations in its membrane where vesicles have fused and released their contents. Multiple neurotransmitter molecules (blue circles) are dispersed throughout the synaptic cleft. Some neurotransmitter molecules are shown binding to receptors on the postsynaptic membrane, with blue circles positioned at the receptor binding sites. This panel demonstrates how neurotransmitters bridge the synaptic cleft to transmit signals from the presynaptic to the postsynaptic neuron.

Animation 8.4

This animation illustrates the sequence of events during neurotransmitter release at a chemical synapse. The animation begins with a presynaptic terminal containing synaptic vesicles filled with neurotransmitter molecules, separated from the postsynaptic membrane by the synaptic cleft. The postsynaptic membrane contains neurotransmitter receptors. When an action potential propagates down the axon and reaches the presynaptic terminal, voltage-gated calcium channels in the terminal membrane open. Calcium ions flow into the presynaptic terminal through these channels. The calcium influx triggers the synaptic vesicles to fuse with the presynaptic membrane through exocytosis. As the vesicles fuse, they release their neurotransmitter contents into the synaptic cleft. The animation shows neurotransmitter molecules diffusing across the synaptic cleft from the presynaptic to the postsynaptic membrane. The neurotransmitters bind to receptors embedded in the postsynaptic membrane, causing these receptors to open or initiate signaling cascades. This binding initiates the postsynaptic response, which could be excitatory or inhibitory depending on the neurotransmitter and receptor type. The animation demonstrates the key features of chemical synaptic transmission: the spatial separation between neurons, the calcium-dependent release mechanism, the synaptic delay as neurotransmitters diffuse across the cleft, and the unidirectional nature of transmission from the neurotransmitter-releasing presynaptic cell to the receptor-containing postsynaptic cell.

Figure 8.3

This figure illustrates three types of chemical synapses classified by their postsynaptic target location using three panels labeled A, B, and C. Each panel shows a presynaptic neuron on the left with typical morphology including dendrites and cell body, and a myelinated axon (shown as segments of gray ovals) extending to the right toward a postsynaptic neuron. Panel A demonstrates an axodendritic synapse, where the presynaptic terminal contacts the dendrites of the postsynaptic neuron. The postsynaptic cell displays branching dendrites (highlighted in green) extending from the cell body. The myelinated axon from the presynaptic cell terminates at and forms synaptic connections with these dendritic branches. Panel B shows an axosomatic synapse, where the presynaptic terminal makes contact with the cell body (soma) of the postsynaptic neuron. The postsynaptic cell body is highlighted in green, indicating the synaptic contact site. The presynaptic myelinated axon extends to and synapses directly onto the soma rather than the dendrites. Panel C illustrates an axoaxonic synapse, where the presynaptic terminal contacts the axon of the postsynaptic neuron. The postsynaptic neuron’s axon is highlighted in green at the synaptic contact point, showing where the presynaptic terminal forms connections directly onto the axon rather than dendrites or soma. This arrangement allows the presynaptic neuron to modulate action potential propagation in the postsynaptic axon.

Chapter 9 – Neurotransmitter Synthesis and Storage

Figure 9.1

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 9.2

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 9.3

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 9.4

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 9.5

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 9.6

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 9.7

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 9.8

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 9.9

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 9.10

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 9.11

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 9.12

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 10 – Neurotransmitter Release

Chapter 10: Neurotransmitter Release – Detailed Alternative Text

Animation 10.1

This animation demonstrates calcium influx into the presynaptic terminal during an action potential. The animation shows a cross-section of the terminal membrane with voltage-gated sodium channels (blue dotted) and voltage-gated calcium channels (purple striped) embedded in the bilayer. When the action potential reaches the terminal, voltage-gated sodium channels open first, allowing sodium ions (blue circles with positive charges) to flow into the terminal down their electrochemical gradient. This sodium influx depolarizes the terminal membrane. The depolarization triggers voltage-gated calcium channels to open. Calcium ions (shown as circles) then flow into the terminal down their strong electrochemical gradient. The calcium gradient is powerful because calcium concentration outside the cell is much higher than inside, and the negative interior attracts the positive calcium ions. This calcium influx is the critical trigger for neurotransmitter release.

Animation 10.2

This animation shows synaptotagmin’s role as a calcium sensor in exocytosis. A docked synaptic vesicle is positioned at the terminal membrane through SNARE protein interactions (synaptobrevin on the vesicle, SNAP-25 and syntaxin on the terminal membrane). Voltage-gated calcium channels (purple striped) are nearby. When calcium channels open, calcium ions flow into the terminal. Synaptotagmin, a protein embedded in the vesicle membrane, contains calcium-binding domains that detect calcium entry. When calcium binds to synaptotagmin, the protein undergoes a conformational change and interacts with the SNARE protein complex. This calcium-dependent synaptotagmin-SNARE interaction is the first step toward membrane fusion. The animation demonstrates how calcium acts as the crucial signal linking electrical activity (the action potential) to the mechanical process of vesicle fusion and neurotransmitter release.

Figure 10.1

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 10.2

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 10.3

This animation illustrates the complete exocytosis process during neurotransmitter release. A vesicle containing neurotransmitter molecules (blue circles) is docked at the terminal membrane via SNARE proteins. Voltage-gated calcium channels (purple striped) open, allowing calcium to enter. Calcium binds to synaptotagmin, which then interacts with the SNARE complex. This interaction pulls the vesicle and terminal membranes together. The lipid bilayers merge, forming a fusion pore connecting the vesicle interior to the synaptic cleft. The vesicle membrane fuses completely with the terminal membrane, creating an opening through which neurotransmitter molecules are released into the synaptic cleft. The neurotransmitters diffuse across the cleft toward the postsynaptic membrane. This demonstrates the calcium-dependent fusion mechanism that converts electrical signals into chemical communication between neurons. The entire process occurs rapidly, within milliseconds of calcium entry.