CH 35 Comprehensive Study Guide to Neurons, Glia, and the Nervous System

Evolutionary Diversity of Nervous Systems

Nervous systems across the animal kingdom exhibit a wide range of structural complexity. Some organisms, such as sea sponges, lack a true nervous system entirely. Cnidarians, such as jellyfish, do not possess a true brain but utilize a decentralized system of separate but connected nerve cells known as a ‐nerve net.‐ Echinoderms, including sea stars, have nerve cells bundled into fibers called nerves. Flatworms of the phylum Platyhelminthes demonstrate increased complexity with a central nervous system (CNS) consisting of a small ‐brain‐ and two nerve cords, alongside a peripheral nervous system (PNS) with nerves extending through the body. Insects possess a more complex yet decentralized system containing a brain, a ventral nerve cord, and ganglia, which are clusters of connected neurons that can control behaviors independently of the brain. Octopi have highly sophisticated invertebrate nervous systems, featuring neurons organized in specialized lobes and eyes structurally similar to those of vertebrates. Compared to invertebrates, vertebrate nervous systems are more centralized, complex, and specialized, featuring a CNS with a brain and spinal cord and a PNS of sensory and motor nerves. A notable evolutionary difference is the location of the nerve cord: many invertebrates have ventral nerve cords, while vertebrate spinal cords are located dorsally. Evolutionary biologists like Mark Kirschner discuss the ‐flipping‐ phenomenon, debating if these arrangements evolved separately or if the invertebrate body plan arrangement flipped during vertebrate evolution.

Cellular Components: Neurons and Glia

The nervous system is composed of two primary cell types: neurons and glia. Neurons are specialized cells that receive and transmit chemical or electrical signals, while glia provide essential support functions and play an information-processing role complementary to neurons. A neuron is often compared to an electrical wire, while glia are compared to electric company workers who maintain and route these wires, though recent evidence suggests glia also perform some signaling functions. The quantity of neurons varies significantly by species: the laboratory fly Drosophila melanogaster has approximately $100,000$ neurons, as does a lobster; a mouse has $75 \times 10^6$; an octopus has $300 \times 10^6$; and the human brain contains approximately $86 \times 10^9$ neurons. Despite these numerical differences, the underlying ability of neurons to communicate allows these animals to control similar behaviors, such as finding food or courting mates. Glial cells actually outnumber neurons in the brain by a factor of ten. They guide developing neurons, buffer harmful ions and chemicals, and provide myelin sheaths. Dysfunction in glia is a primary cause of most brain tumors.

Structural Components and Classification of Neurons

Neurons share common cellular organelles, including a cytoplasm-filled cell body (soma) containing a nucleus, smooth and rough endoplasmic reticulum, Golgi apparatus, and mitochondria. They also possess unique structures for communication. Dendrites are tree-like extensions that receive messages from other neurons at specialized junctions called synapses; some possess dendritic spines to increase surface area. The axon hillock integrates signals from multiple synapses and acts as the junction between the soma and the axon. The axon is a tube-like structure that propagates signals to axon terminals, which synapse onto other neurons, muscles, or organs. Some neurons, like amacrine cells in the retina, lack axons. Many axons are covered in myelin, an insulator produced by glia that minimizes signal dissipation and increases conduction speed. Gaps in the myelin are called nodes of Ranvier, where the signal is ‐recharged.‐ Neurons are broadly divided into four types: unipolar neurons (one structure extending from the soma, found in insects); bipolar neurons (one axon and one dendrite, e.g., retinal bipolar cells); multipolar neurons (one axon and multiple dendrites, the most common type, e.g., Purkinje cells in the cerebellum, which can receive signals from up to $200,000$ other neurons); and pseudounipolar cells (a single process that later branches into two, found in most sensory neurons).

Neurogenesis and Identification Techniques

Contrary to older scientific beliefs, neurogenesis (the birth of new neurons) continues into adulthood. This was first discovered in songbirds and later in mammals, where approximately $1000$ new neurons develop in the hippocampus daily. Survival of these neurons in the hippocampus is correlated with learning efficiency in tasks. Factors like exercise and certain antidepressants promote neurogenesis, while stress inhibits it. Researchers identify these new cells by injecting bromodeoxyuridine (BrdU) into the brain. BrdU is only incorporated into the DNA of cells in the S phase of division. Immunohistochemistry is then used to attach fluorescent labels to the BrdU for visualization via microscopy. In micrographs, cells expressing glial fibrillary acidic protein (GFAP) label green (astrocytes), while those with BrdU label red (newly dividing cells). Cells that are red only are newly born neurons.

Specific Types and Functions of Glial Cells

Glial cells are categorized by their location and specific roles. In the Central Nervous System (CNS), astrocytes contact both capillaries and neurons to provide nutrients, regulate ion concentrations in the extracellular fluid, provide structural support for synapses, and form the blood-brain barrier (BBB). Calcium imaging shows astrocytes modulate synaptic activity. Microglia scavenge dead cells and protect against microorganisms. Oligodendrocytes form myelin sheaths; one oligodendrocyte can myelinate multiple neurons. Ependymal cells line the ventricles and central canal, producing cerebrospinal fluid (CSF). Radial glia act as scaffolds for migrating neurons. In the Peripheral Nervous System (PNS), satellite glia provide nutrients and structural support, while Schwann cells provide myelin for a single axon by surrounding it entirely.

The Resting Membrane Potential

Neuronal communication depends on a charged cellular membrane. The lipid bilayer is impermeable to ions, requiring ion channels (including voltage-gated channels) for transport. The difference in charge between the inside and outside of the cell is the membrane potential. A neuron at rest is negatively charged, typically at approximately $-70\,mV$ relative to the outside. This resting membrane potential is maintained by the concentration gradients of ions and the actions of the sodium-potassium pump, which moves $3\,Na^+$ out and $2\,K^+$ in per ATP consumed. Potassium leakage channels are more numerous than sodium leakage channels, allowing $K^+$ to diffuse out faster than $Na^+$ leaks in, creating a net negative interior. Typical concentrations are:

$Na^+_{extracellular} = 145\,mM$, $Na^+_{intracellular} = 12\,mM$

$K^+_{extracellular} = 4\,mM$, $K^+_{intracellular} = 155\,mM$

$Cl^-_{extracellular} = 120\,mM$, $Cl^-_{intracellular} = 4\,mM$

Organic anions ($A^-$) are concentrated $\text{intracellularly at approximately } 100\,mM$, helping to maintain the negative charge as they are repelled by chloride ions.

The Physiology and Propagation of Action Potentials

An action potential is a brief reversal of the resting membrane potential. It begins when a stimulus depolarizes the membrane to a threshold potential of $-55\,mV$. At this point, voltage-gated $Na^+$ channels at the axon hillock open, allowing $Na^+$ to rush in and depolarize the cell to approximately $+40\,mV$. Action potentials are ‐all-or-nothing‐ events. To reset, $Na^+$ channels close and enter a refractory period, while voltage-gated $K^+$ channels open. The exit of $K^+$ repolarizes and eventually hyperpolarizes the membrane (making it more negative than the resting potential). Conduction speed is increased by larger axon diameters and myelin insulation. In myelinated axons, action potentials ‐jump‐ between nodes of Ranvier in a process called saltatory conduction, which saves energy and speeds transmission. Demyelinating diseases like multiple sclerosis slow this conduction due to current leaks.

Synaptic Transmission and Signal Summation

Information is transmitted at the synapse. In chemical synapses, an action potential reaches the terminal, opening voltage-gated $Ca^{2+}$ channels. The influx of $Ca^{2+}$ causes synaptic vesicles to fuse with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft. These chemicals bind to ligand-gated ion channels on the postsynaptic membrane. Excitatory postsynaptic potentials (EPSPs), often caused by acetylcholine opening $Na^+$ channels, depolarize the membrane. Inhibitory postsynaptic potentials (IPSPs), caused by GABA opening $Cl^-$ channels, hyperpolarize it. Neurotransmitters are removed via diffusion, enzymatic degradation (e.g., acetylcholinesterase), or reuptake. Summation occurs at the axon hillock, where all EPSPs and IPSPs are added together; an action potential fires only if the net change reaches the threshold. Electrical synapses involve direct physical connections via gap junctions, allowing instantaneous and sometimes bidirectional signaling, crucial for reflexes and synchronizing neuronal groups, such as those in the thalamus regulating sleep.

Long-Term Potentiation (LTP) and Depression (LTD)

Synaptic plasticity is the basis of learning and memory. Long-term potentiation (LTP) is the persistent strengthening of a synapse, following the Hebbian principle: ‐cells that fire together wire together.‐ One mechanism involves NMDA receptors, which are normally blocked by $Mg^{2+}$. Rapid depolarization expels $Mg^{2+}$, allowing $Ca^{2+}$ influx, which triggers a signaling cascade that inserts more AMPA receptors into the postsynaptic membrane, making it more responsive to glutamate. Long-term depression (LTD) is the reverse: low-frequency stimulation causes a different $Ca^{2+}$ cascade that results in the endocytosis (removal) of AMPA receptors. LTD is essential for pruning unused synapses and enhancing the relative strength of LTP-modified synapses.

Anatomy and Protection of the CNS

The CNS comprises the brain and spinal cord, protected by three meningeal layers: the tough outer dura mater, the web-like arachnoid mater, and the delicate pia mater. The subarachnoid space and the brain‐s ventricles are filled with cerebrospinal fluid (CSF), produced by the choroid plexus. CSF provides buoyancy and shock absorption; the human brain contains about 8.5\,tablespoons of it. A blockage in the ventricles leads to hydrocephalus. The brain can be viewed through sagittal, coronal, or horizontal sections. The cerebral cortex is characterized by folds (gyri) and valleys (sulci). The two hemispheres are connected by the corpus callosum. Split-brain patients, whose corpus callosum has been severed, demonstrate functional localization; for instance, they may be unable to name objects seen in the left visual field because the information cannot reach the speech center in the left hemisphere.

Brain Lobes and Subcortical Structures

The cerebral cortex has four lobes: the frontal lobe (olfactory bulb, motor cortex for movement planning, cognitive functions like attention and speech); the parietal lobe (somatosensation like touch and heat, and proprioception); the occipital lobe (vision); and the temporal lobe (sounds, memory formation via the hippocampus). Subcortical structures include the basal ganglia (posture and movement control; damage causes Parkinson‐s-like symptoms); the thalamus (gateway for sensory/motor inputs and consciousness regulation); and the hypothalamus (controls the endocrine system via the pituitary gland, acts as the body‐s thermostat, and regulates circadian rhythms). The limbic system, including the amygdala, regulates emotion and fear. The cerebellum sits at the base of the brain, controlling balance and motor learning. The brainstem (midbrain, medulla oblongata, and pons) coordinates basic life functions like breathing and heart rate.

The Spinal Cord and Peripheral Nervous System

The spinal cord carries information between the brain and body. It contains white matter (myelinated axons) and butterfly-shaped gray matter (cell bodies and interneurons). Dorsal axons carry sensory information, while ventral axons transmit motor signals. The spinal cord also handles fast reflexes, such as the knee-jerk reflex, involving direct synapses between sensory and motor neurons. The PNS consists of the autonomic nervous system and the sensory-somatic nervous system. The autonomic system is divided into the sympathetic nervous system (‐fight or flight,‐ releasing norepinephrine on targets) and the parasympathetic nervous system (‐rest and digest,‐ releasing acetylcholine). The sensory-somatic system includes $12$ cranial nerves (e.g., olfactory, oculomotor, glossopharyngeal) and $31$ pairs of spinal nerves. Sensory neuron cell bodies are located in the dorsal root ganglia.

Neurological and Mental Disorders

Neurodegenerative disorders involve progressive neuronal death. Alzheimer‐s disease, the most common dementia, is characterized by amyloid plaques, neurofibrillary tangles, and hippocampal shrinkage. One risk factor is the APOE E4 gene variant. Parkinson‐s disease results from the loss of dopamine neurons in the substantia nigra, characterized by Lewy bodies and tremors; it is treated with L-DOPA. Neurodevelopmental disorders include Autism Spectrum Disorder (ASD), characterized by impaired social skills and repetitive behaviors, and Attention Deficit/Hyperactivity Disorder (ADHD), linked to prefrontal cortex dysfunction. Mental illnesses include schizophrenia (malfunctioning dopamine and glutamate signaling, treated with antipsychotics) and major depression (often linked to the monoamine hypothesis, treated with SSRIs or MAOIs). Other conditions include epilepsy (recurrent seizures) and stroke (blood flow disruption to the brain), which is the third most common cause of death in the United States, occurring every 40\,seconds on average.

Questions & Discussion

Question: Which of the following statements is false? a. The soma is the cell body of a nerve cell. b. Myelin sheath provides an insulating layer to the dendrites. c. Axons carry the signal from the soma to the target. d. Dendrites carry the signal to the soma. Answer: b. (Myelin provides insulation to the axon, not the dendrites).

Question: Which part of the action potential would you expect potassium channels to affect? Answer: Potassium channels primarily affect repolarization and hyperpolarization (steps $3, 4, \text{ and } 5$).

Question: Which of the following statements is false regarding the autonomic nervous system? a. The parasympathetic pathway is responsible for resting the body, while the sympathetic pathway is responsible for preparing for an emergency. b. Most preganglionic neurons in the sympathetic pathway originate in the spinal cord. c. Slowing of the heartbeat is a parasympathetic response. d. Parasympathetic neurons are responsible for releasing norepinephrine on the target organ, while sympathetic neurons are responsible for releasing acetylcholine. Answer: d. (In reality, parasympathetic neurons release acetylcholine on the target organ, and sympathetic neurons release norepinephrine).