Neurons, Synapses, and Signaling

Overview of Chapter 48: Neurons, Synapses, and Signaling

• Central Themes: The chapter covers the structural and functional aspects of neurons, how resting potentials are formed, the mechanics of action potentials, and the processes of chemical and electrical communication at synapses.
• Main Topics:     * Neuron structure and organization in relation to function.     * Formation of the resting potential via ion pumps and channels.     * The nature of depolarizations and hyperpolarizations.     * Stages and properties of the action potential.     * Conduction mechanisms of action potentials along axons.     * The function of chemical synapses and postsynaptic potentials (EPSPs and IPSPs).     * A comprehensive survey of major neurotransmitters.

Neuron Structure and Organization in Information Transfer

• Basic Information Transmission: A neuron functions by receiving information, transmitting it along an axon, and passing that information to other cells (such as another neuron or an effector cell) through specialized junctions called synapses.
• Neuron Components:     * Dendrites: Branched extensions that receive signals from other neurons.     * Cell Body: Contains the nucleus and most organelles; serves as the site for integration.     * Axon Hillock: The cone-shaped base of an axon where signals are typically generated.     * Axon: An extension that transmits electrical signaling (output) away from the cell body toward other cells.     * Synaptic Terminal: The end of an axon branch that forms a synapse.     * Synapse: The junction where a neuron communicates with a postsynaptic cell.     * Neurotransmitters: Chemical messengers that pass information across the synaptic cleft.     * Presynaptic Cell: The transmitting neuron.     * Postsynaptic Cell: The neuron, muscle, or gland cell that receives the signal.
• Higher-Level Nervous System Organization:     * Central Nervous System (CNS): Consists of the brain and spinal cord. It is the site where integration of information occurs.     * Peripheral Nervous System (PNS): Consists of cranial nerves, spinal nerves, and ganglia outside the CNS. It is responsible for bringing information into and out of the CNS.

Information Processing Stages and Neuron Types

• Information Processing Stages:     * Sensory Input: Sensors (e.g., in a siphon or proboscis) detect external and internal stimuli and transmit information to the CNS.     * Integration: Processing center where information from sensory inputs is interpreted and associated.     * Motor Output: Signals are sent to effectors (muscles or glands) to trigger a response.
• Specific Neuron Types:     * Sensory Neurons: Transmit information about external stimuli (light, touch, sound) and internal conditions (blood pressure, muscle tension).     * Interneurons: Highly branched neurons that integrate sensory input; they connect neurons but do not directly contact sensors or effectors.     * Motor Neurons: Transmit signals to muscle cells or glands to cause activity.
• Glia: Supporting cells of the nervous system. The diagram indicates a scale of $80\,\mu m$ for glia surrounding neuron cell bodies.

Formation of the Resting Potential through Ion Pumps and Channels

• Membrane Potential: The difference in voltage (electrical charge) across the plasma membrane. Messages are transmitted through the nervous system as changes in this membrane potential.
• Resting Potential: The membrane potential of a neuron that is not currently sending signals. For most neurons, this value is typically between $-60\,mV$ and $-80\,mV$.
• Distribution of Ions:     * The inside of the neuron has a net negative charge relative to the outside.     * Concentration gradients are established primarily for Potassium ($K^+$) and Sodium ($Na^+$) ions.     * Sodium-Potassium ($Na^+/K^+$) Pump: Uses ATP energy to maintain gradients by pumping $Na^+$ out of the cell and $K^+$ into the cell.
• Ion Channels:     * Channels allow ions to diffuse across the membrane.     * A resting neuron has many open $K^+$ channels (leak channels) and very few open $Na^+$ channels.     * The diffusion of $K^+$ out of the cell is the critical factor in forming the resting potential.     * Large anions (negative charges) trapped inside the cell contribute to the internal negative charge as $K^+$ leaves.

Modeling the Resting Potential via Selective Permeability

• The Nernst Equation and Equilibrium Potentials: Potential is always measured as the charge on the inside of the cell.
• Potassium Modeling:     * Inner chamber: $140\,mM\,KCl$     * Outer chamber: $5\,mM\,KCl$     * When the membrane is selectively permeable only to $K^+$, the equilibrium potential ($E_K$) is:     * $E_K = 62\,mV \log\left(\frac{5\,mM}{140\,mM}\right) = -90\,mV$
• Sodium Modeling:     * Inner chamber: $15\,mM\,NaCl$     * Outer chamber: $150\,mM\,NaCl$     * When the membrane is selectively permeable only to $Na^+$, the equilibrium potential ($E_{Na}$) is:     * $E_{Na} = 62\,mV \log\left(\frac{150\,mM}{15\,mM}\right) = +62\,mV$

Action Potentials: The Signals Conducted by Axons

• Gated Ion Channels: Neurons contain channels that open or close in response to stimuli (voltage changes, chemical ligands, or physical stretch). This gating is the basis of electrical signaling.
• Voltage-Gated Ion Channels: Open or close specifically in response to a change in the membrane potential.
• Hyperpolarization: An increase in the magnitude of the membrane potential (making the inside more negative). This can be produced by stimuli that increase the membrane permeability to $K^+$.
• Depolarization: A reduction in the magnitude of the membrane potential (making the inside less negative). This can be produced by stimuli that increase the membrane permeability to $Na^+$.

Graded Potentials versus Action Potentials

• Graded Potentials: Changes in polarization where the magnitude of the change varies continuously with the strength of the stimulus. They decay over distance.
• Action Potential (AP): A massive, rapid change in membrane potential caused by a depolarization that reaches a specific value called the threshold.
• Threshold: In mammalian neurons, the threshold is approximately $-55\,mV$.
• All-or-None Response: Once the threshold is crossed, an AP occurs with a constant magnitude regardless of the initial stimulus strength. APs are the primary signals carrying information along axons.
• Positive Feedback Loop: Depolarization opens voltage-gated $Na^+$ channels, causing $Na^+$ to flow in, which causes further depolarization, opening even more $Na^+$ channels.

Detailed Stages of the Action Potential and Refractory Period

• Duration: An AP lasts about $1-2\,msec$, allowing neurons to produce hundreds of APs per second. Information is conveyed by the frequency of APs.
• Step-by-Step Cycle:     1. Resting State: Both gated $Na^+$ and $K^+$ channels are closed.     2. Depolarization: A stimulus opens some $Na^+$ channels; if the threshold is reached, an AP is triggered.     3. Rising Phase: Most voltage-gated $Na^+$ channels open, causing a rapid influx of $Na^+$ while $K^+$ channels remain closed.     4. Falling Phase: Voltage-gated $Na^+$ channels become inactivated (via an inactivation loop), and voltage-gated $K^+$ channels open, allowing $K^+$ to flow out of the cell.     5. Undershoot (Hyperpolarization): $Na^+$ channels close but some $K^+$ channels remain open. As $K^+$ channels finish closing, the membrane returns to the resting state.
• Refractory Period: A period after an AP during which a second AP cannot be initiated. This is caused by the temporary inactivation of $Na^+$ channels during the falling phase and early undershoot.

Conduction and Propagation of Action Potentials

• Regeneration: An AP travels long distances by regenerating itself at successive positions along the axon. The current from a generated AP at the axon hillock depolarizes the neighboring membrane section.
• Directionality: APs travel in only one direction (toward synaptic terminals) because the inactivated $Na^+$ channels behind the zone of depolarization prevent backward travel.
• Conduction Velocity Enhancement:     * Myelin Sheaths: Insulating layers produced by glia—Oligodendrocytes in the CNS and Schwann cells in the PNS. Myelin layers have a thickness/scale around $0.1\,\mu m$.     * Nodes of Ranvier: Gaps in the myelin sheath where voltage-gated $Na^+$ channels are concentrated. APs form only at these nodes.     * Saltatory Conduction: The process where APs in myelinated axons "jump" from node to node, significantly increasing the speed of conduction.

Communication Between Neurons at Synapses

• Electrical Synapses: Electrical current flows directly from one neuron to another through gap junctions.
• Chemical Synapses: The most common type of synapse, where a chemical neurotransmitter carries the signal across the synaptic cleft.
• Mechanism of Neurotransmitter Release:     1. An AP arrives at the synaptic terminal and depolarizes the presynaptic membrane.     2. This depolarization opens voltage-gated $Ca^{2+}$ channels.     3. $Ca^{2+}$ enters the terminal, causing synaptic vesicles containing neurotransmitters to fuse with the presynaptic membrane.     4. Neurotransmitters are released into the synaptic cleft, diffuse across it, and bind to receptors on the postsynaptic membrane.

Generation and Summation of Postsynaptic Potentials

• Ligand-Gated Ion Channels: Neurotransmitters bind to these channels on the postsynaptic cell, causing specific ions to flow and generating a postsynaptic potential (PSP).
• Categories of Postsynaptic Potentials:     1. Excitatory Postsynaptic Potentials (EPSPs): Depolarizations that move the membrane potential closer to the threshold.     2. Inhibitory Postsynaptic Potentials (IPSPs): Hyperpolarizations that move the membrane potential further from the threshold.
• Summation Mechanics:     * Temporal Summation: Occurs when two EPSPs are produced in rapid succession by a single synapse, adding their effects together.     * Spatial Summation: Occurs when EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron add together.     * Interaction: An IPSP can counter the effect of an EPSP. The axon hillock acts as the integration center; if the summed potential reaches the threshold, an AP is generated.

Termination of Neurotransmitter Signaling

• Signaling Cessation: To prevent continuous stimulation, neurotransmitters must be removed from the synaptic cleft.
• Two Main Mechanisms:     1. Enzymatic Breakdown: Targeted destruction by enzymes (e.g., acetylcholinesterase inactivating acetylcholine).     2. Reuptake: The presynaptic neuron recaptures the neurotransmitter through neurotransmitter transport channels for recycling.

Survey of Major Neurotransmitters and Their Effects

• Acetylcholine (ACh):     * Common in vertebrates and invertebrates.     * Functions: Muscle contraction/relaxation (neuromuscular junctions), memory formation, and learning.     * Termination: Acetylcholinesterase (AChE).     * Toxins/Inhibitors:         * Botulinum toxin: Prevents ACh release, causing flaccid paralysis.         * Curare and Hemlock: Inhibit the acetylcholine receptor (AChR).         * Sarin (nerve gas): AChE inhibitor, leading to spastic paralysis due to ACh build-up.
• Amino Acids:     * Glutamate: Major excitatory neurotransmitter in the CNS; involved in long-term memory.     * Gamma-aminobutyric acid (GABA): Major inhibitory neurotransmitter in the CNS; stimulates IPSPs.
• Biogenic Amines (Active in CNS and PNS):     * Includes Epinephrine, Norepinephrine, Dopamine, and Serotonin.     * Dopamine and Serotonin influence sleep, mood, and learning.     * Psychoactive drugs like LSD and Mescaline cause hallucinations by activating dopamine and serotonin receptors.
• Neuropeptides:     * Substance P and Endorphins: Affect the perception of pain.     * Opiates (Morphine, Heroin): Mimic endorphins by binding to the same receptors; used as painkillers.
• Gases:     * Nitric oxide (NO) and Carbon monoxide (CO) act as local regulators within the PNS.