Premed · Premed · General Biology 2
Lecture 21: The Nervous System — Neurons and Signaling
General Biology II — Organismal, Evolution & Ecology
Learning Objectives
By the end of this lecture, students will be able to:
- Describe the structure and function of a neuron and its major components
- Explain how resting membrane potential is established and maintained
- Describe the ionic basis of the action potential and its propagation along an axon
- Explain saltatory conduction and the role of myelination
- Describe synaptic transmission including the roles of neurotransmitters
- Compare the organization and functions of the central and peripheral nervous systems
- Distinguish between the somatic and autonomic divisions of the peripheral nervous system
Lecture Content
I. Overview of the Nervous System
The nervous system detects stimuli from the internal and external environment, integrates that information, and coordinates appropriate responses. It is divided into two major anatomical components. The central nervous system (CNS) -- the brain and spinal cord -- serves as the integration and processing center. The peripheral nervous system (PNS) -- consisting of 12 pairs of cranial nerves and 31 pairs of spinal nerves -- connects the CNS to the rest of the body.
The PNS is further divided by function. The sensory (afferent) division carries signals from receptors throughout the body to the CNS. The motor (efferent) division transmits commands from the CNS to effectors such as muscles and glands. Within the motor division, the somatic nervous system provides voluntary control over skeletal muscle, while the autonomic nervous system (ANS) governs involuntary functions of smooth muscle, cardiac muscle, and glands. The ANS itself has three branches: the sympathetic division, which mobilizes the body for action ("fight or flight") by increasing heart rate, dilating pupils, and inhibiting digestion; the parasympathetic division, which promotes maintenance activities ("rest and digest") by decreasing heart rate, constricting pupils, and stimulating digestion; and the enteric nervous system, an intrinsic network of neurons embedded in the walls of the gastrointestinal tract that can coordinate digestive function independently of the CNS.
II. Neuron Structure
The neuron is the functional unit of the nervous system. The cell body (soma) contains the nucleus and most organelles and serves as the metabolic center. Dendrites are highly branched extensions that receive incoming signals from other neurons or sensory receptors, bearing ligand-gated ion channels at their surfaces. The axon hillock, at the junction between the soma and the axon, is the trigger zone for action potential initiation and contains the highest density of voltage-gated sodium channels. The axon is a single long extension that conducts action potentials away from the cell body -- motor neuron axons can reach lengths of up to one meter. Within the axon, organelles and vesicles are transported along microtubules by motor proteins: kinesin carries cargo anterogradely (toward the axon terminal) and dynein carries it retrogradely (back toward the cell body).
Many axons are wrapped in a myelin sheath, an insulating lipid-rich layer that dramatically increases the speed of signal transmission. In the PNS, myelin is formed by Schwann cells, with one Schwann cell wrapping a single internode. In the CNS, oligodendrocytes provide myelination, with each oligodendrocyte myelinating segments of multiple axons. The gaps between myelin segments are called nodes of Ranvier, where the axon membrane is exposed and voltage-gated sodium channels are concentrated. At the distal end, the axon branches into axon terminals (synaptic boutons), swollen tips packed with synaptic vesicles containing neurotransmitter molecules.
Neurons are classified functionally into three types: sensory (afferent) neurons carry signals toward the CNS, motor (efferent) neurons carry signals from the CNS to effectors, and interneurons connect neurons within the CNS for integration and processing. Supporting the neurons are glial cells (neuroglia), which outnumber neurons by roughly 10 to 1. Astrocytes maintain the blood-brain barrier, regulate extracellular potassium and neurotransmitter concentrations, and provide metabolic support. Microglia serve as the immune cells of the CNS, phagocytosing debris and pathogens. Ependymal cells line the brain ventricles, producing and circulating cerebrospinal fluid.
<image>A detailed diagram of neuron structure. The main panel shows a motor neuron with all major components labeled: cell body (soma) containing the nucleus and Nissl bodies (rough ER), multiple branching dendrites extending from the soma, the axon hillock at the junction of soma and axon, a long axon wrapped in a myelin sheath with regularly spaced nodes of Ranvier, and axon terminals (synaptic boutons) at the distal end. An inset on the upper right shows a cross-section of the myelinated axon with concentric layers of Schwann cell membrane forming the myelin sheath, the axon in the center, and the node of Ranvier where the axon membrane is exposed. A second inset on the lower right shows a magnified view of the synaptic terminal containing mitochondria and synaptic vesicles clustered near the presynaptic membrane, facing the synaptic cleft and postsynaptic membrane with receptors.</image>
III. Resting Membrane Potential
The resting membrane potential is the voltage difference across the plasma membrane of a neuron that is not being stimulated, typically about -70 mV (the interior is negative relative to the exterior). This electrical gradient arises from the unequal distribution of ions: potassium (K+) is concentrated inside the cell while sodium (Na+) is concentrated outside, and large organic anions (proteins and amino acids) are trapped within the cytoplasm. The Na+/K+-ATPase (sodium-potassium pump) actively maintains these concentration gradients by pumping three Na+ ions out of the cell and two K+ ions in for every molecule of ATP hydrolyzed. This electrogenic pump also contributes a small amount directly to the negative resting potential.
At rest, the membrane is selectively permeable because K+ leak channels are open while most Na+ channels remain closed. Potassium ions diffuse outward down their concentration gradient, leaving behind the negatively charged organic anions and creating the negative resting potential. The equilibrium potential for K+ (E_K), calculated by the Nernst equation, is approximately -90 mV, while the equilibrium potential for Na+ (E_Na) is approximately +60 mV. The resting membrane potential of -70 mV sits closer to E_K because the membrane's permeability to K+ is roughly 50 to 100 times greater than its permeability to Na+ at rest. The Goldman equation extends this analysis by calculating the membrane potential from the permeabilities and concentrations of multiple ions simultaneously -- principally Na+, K+, and Cl-.
IV. The Action Potential
An action potential is a rapid, transient reversal of membrane polarity that propagates along the axon as the fundamental unit of neural signaling. It obeys the all-or-none principle: if the membrane potential reaches threshold (typically around -55 mV), the action potential fires at full amplitude; stimuli below threshold produce no action potential at all.
The action potential proceeds through a sequence of phases. In the resting state, all voltage-gated Na+ and K+ channels are closed and the membrane sits at -70 mV. When a stimulus depolarizes the membrane to threshold, voltage-gated Na+ channels open rapidly in a self-reinforcing cycle of positive feedback -- depolarization drives the membrane potential sharply upward, toward +30 to +40 mV as Na+ rushes into the cell, approaching E_Na. Within about one millisecond, the Na+ channels inactivate (their inactivation gates close) and voltage-gated K+ channels, which open with a slight delay, allow K+ to rush out, driving repolarization back toward the resting potential. Because the K+ channels are slow to close, the membrane briefly dips below -70 mV during a transient hyperpolarization (undershoot), approaching E_K at about -90 mV. The Na+/K+-ATPase and leak channels then restore the resting ion distributions.
Two refractory periods follow each action potential. During the absolute refractory period, Na+ channels are inactivated and no stimulus, however strong, can trigger another action potential -- this ensures that the signal propagates in only one direction along the axon. During the relative refractory period, some Na+ channels have recovered but K+ channels remain open, so a stronger-than-normal stimulus can elicit an action potential, though at reduced amplitude; this period limits the maximum firing frequency.
<image>A multi-panel figure illustrating the action potential. Panel A: A voltage-versus-time graph of the action potential showing resting potential at -70 mV, threshold at -55 mV, depolarization rising to approximately +35 mV, repolarization falling steeply, hyperpolarization (undershoot) dipping below -70 mV, and return to resting potential. Each phase is labeled with a numbered marker. Panel B: A series of four membrane cross-section diagrams corresponding to the numbered phases, showing the states of voltage-gated Na+ channels (closed, open, inactivated) and voltage-gated K+ channels (closed, open) at each phase, with arrows indicating ion flow direction. Na+ enters during depolarization, K+ exits during repolarization. Panel C: A horizontal bar below the graph indicating the absolute refractory period (aligned with depolarization and early repolarization) and the relative refractory period (aligned with late repolarization and hyperpolarization).</image>
V. Action Potential Propagation
The action potential propagates along the axon through local current flow. Sodium ions entering at the site of depolarization spread to adjacent regions of the membrane, depolarizing them to threshold and triggering the opening of Na+ channels there -- effectively regenerating the action potential at each successive point. The absolute refractory period of the region just behind the advancing wavefront prevents backward propagation, ensuring unidirectional travel.
In unmyelinated axons, this regeneration occurs continuously at every point along the membrane, a mode called continuous conduction that is relatively slow (0.5-10 m/s). In myelinated axons, the myelin sheath insulates the internodal regions and prevents ion leakage, so the electrical current effectively jumps from one node of Ranvier to the next -- a process called saltatory conduction. Because action potentials are regenerated only at the nodes, where voltage-gated Na+ channels are densely concentrated, saltatory conduction is both much faster (up to 120 m/s) and more energy-efficient, since fewer ions cross the membrane and less work is required of the Na+/K+-ATPase. Conduction velocity also increases with axon diameter, which reduces internal resistance to current flow. The clinical significance of myelination is underscored by demyelinating diseases such as multiple sclerosis and Guillain-Barre syndrome, in which damage to the myelin sheath impairs signal conduction and produces weakness, sensory loss, and loss of coordination.
VI. Synaptic Transmission
A synapse is the junction between two neurons or between a neuron and an effector cell. The vast majority of synapses in the nervous system are chemical synapses, which convert an electrical signal into a chemical one and back again.
Chemical synaptic transmission proceeds through a well-defined sequence of steps. An action potential arriving at the axon terminal of the presynaptic neuron opens voltage-gated Ca2+ channels, allowing calcium ions to flood into the terminal. This calcium influx triggers the fusion of synaptic vesicles with the presynaptic membrane through SNARE protein-mediated exocytosis, releasing neurotransmitter molecules into the synaptic cleft -- a narrow gap of approximately 20-40 nm. The neurotransmitter diffuses across the cleft and binds to receptors on the postsynaptic membrane. Ionotropic receptors (ligand-gated ion channels) open directly upon neurotransmitter binding, producing fast responses. Metabotropic receptors (G-protein-coupled receptors) activate intracellular signaling cascades, producing slower but more modulatory effects. The resulting change in the postsynaptic membrane potential constitutes the synaptic signal. Signal termination is accomplished by one of three mechanisms: enzymatic degradation of the neurotransmitter in the cleft (as acetylcholinesterase breaks down acetylcholine), reuptake into the presynaptic terminal by specific transporter proteins (as occurs with serotonin and dopamine), or simple diffusion out of the synaptic cleft.
Postsynaptic potentials come in two forms. An excitatory postsynaptic potential (EPSP) is a depolarization that brings the membrane closer to threshold, typically caused by the opening of Na+ or general cation channels. An inhibitory postsynaptic potential (IPSP) is a hyperpolarization that moves the membrane away from threshold, produced by the opening of Cl- or K+ channels. A single neuron may receive thousands of synaptic inputs simultaneously, and these are integrated at the axon hillock through summation. Temporal summation occurs when rapid successive signals from the same presynaptic neuron add together. Spatial summation occurs when simultaneous signals from multiple presynaptic neurons combine. If the net sum of EPSPs and IPSPs at the axon hillock reaches threshold, an action potential is generated.
The nervous system employs a diverse pharmacopoeia of neurotransmitters. Acetylcholine (ACh) operates at the neuromuscular junction, throughout the autonomic nervous system, and in the CNS, and is broken down by acetylcholinesterase. Glutamate is the principal excitatory neurotransmitter in the CNS, while GABA (gamma-aminobutyric acid) is the principal inhibitory neurotransmitter. Glycine serves as an inhibitory transmitter mainly in the spinal cord. Dopamine is involved in reward, motor control, and motivation. Serotonin (5-HT) modulates mood, sleep, and appetite. Norepinephrine mediates arousal and sympathetic nervous system activity. Endorphins are the body's natural opioids, modulating pain perception.
<image>A detailed diagram of synaptic transmission at a chemical synapse. The left side shows the presynaptic axon terminal in cross-section, containing mitochondria and numerous synaptic vesicles filled with neurotransmitter molecules (shown as small dots). An action potential arriving is indicated by an arrow. Voltage-gated Ca2+ channels are shown opening in the presynaptic membrane, with Ca2+ ions entering and triggering vesicle fusion (exocytosis via SNARE proteins). Neurotransmitter molecules are released into the synaptic cleft (labeled, with the width marked as approximately 20 nm). On the right side, the postsynaptic membrane shows two types of receptors: ionotropic receptors (ligand-gated ion channels) with ions flowing through upon neurotransmitter binding, and metabotropic receptors (G-protein-coupled receptors) activating an intracellular G-protein and second messenger cascade. Below the main diagram, three mechanisms of signal termination are illustrated: enzymatic degradation (an enzyme breaking down the neurotransmitter in the cleft), reuptake (a transporter protein pumping neurotransmitter back into the presynaptic terminal), and diffusion (neurotransmitter molecules drifting away from the synapse).</image>
VII. Organization of the Central Nervous System
The brain is organized into several major regions, each with distinct functions. The cerebrum, the largest part, features the cerebral cortex -- an outer layer of gray matter organized into two hemispheres connected by the corpus callosum. The cortex mediates higher cognitive functions including thought, memory, language, sensory perception, and voluntary movement. The cerebellum coordinates movement, maintains balance, and supports motor learning. The diencephalon contains the thalamus, which serves as the sensory relay station directing incoming information to the appropriate cortical regions, and the hypothalamus, which regulates homeostasis, endocrine function, and autonomic activity. The brainstem -- comprising the midbrain, pons, and medulla oblongata -- controls vital functions such as breathing, heart rate, and blood pressure, and serves as the relay between the brain and spinal cord. The limbic system, including the amygdala (emotion and fear processing), hippocampus (memory formation), and cingulate cortex, integrates emotion and memory.
The spinal cord functions both as a conduit for signals traveling between the brain and the body and as an independent integration center for reflexes. Its inner gray matter, arranged in a butterfly-shaped pattern, contains neuronal cell bodies and interneurons. The surrounding white matter consists of myelinated axon tracts carrying ascending sensory and descending motor information. The reflex arc represents the simplest neural pathway: a receptor detects a stimulus, a sensory neuron carries the signal to an integration center (typically an interneuron in the spinal cord), and a motor neuron transmits the response to an effector -- producing a fast, involuntary reaction.
VIII. The Autonomic Nervous System in Detail
The autonomic nervous system uses a two-neuron pathway from the CNS to each effector organ: a preganglionic neuron (with its cell body in the CNS) synapses in a ganglion with a postganglionic neuron, which then innervates the target tissue. The sympathetic division has preganglionic neurons originating in the thoracic and lumbar spinal cord (thoracolumbar outflow), with short preganglionic fibers and long postganglionic fibers. The preganglionic neurotransmitter is acetylcholine; the postganglionic neurotransmitter is norepinephrine. Sympathetic activation increases heart rate and contractile force, dilates the bronchioles, dilates the pupils, stimulates glycogenolysis, inhibits digestion, and triggers epinephrine release from the adrenal medulla. The parasympathetic division has preganglionic neurons originating in the brainstem and sacral spinal cord (craniosacral outflow), with long preganglionic fibers and short postganglionic fibers. Both the preganglionic and postganglionic neurotransmitter is acetylcholine. Parasympathetic activation decreases heart rate, constricts the bronchioles, constricts the pupils, and stimulates digestion and salivation. Most organs receive dual innervation from both divisions, which exert opposing effects to provide precise antagonistic control of organ function.
