Chapter 2 Notes (Cells of the Brain)

History of brain cells and early limits

Cells discovered in the 1600s; neurons identified much later; early brain tissue was too mushy to study without fixes
Preservatives and fixation techniques needed to study brain structure

Histology: microscopic study of anatomy; focus on structure–function relationships
General steps: fix tissue → stain tissue → slice tissue → visualize tissue
Stains reveal different cellular components and help identify neuron structure

H&E stain: basic visualization of tissue; limitation: neuron identification can be ambiguous
Nissl stain: stains cell bodies (protein-rich areas like rough ER) to highlight neurons
Golgi stain: silver stain that reveals entire neuron morphology (soma, dendrites, axon, terminals)
Golgi staining stains only ~1–5% of neurons, yet reveals complete cellular structure

Reticular theory: brain as a continuous network
Neuron Doctrine: nervous system composed of discrete, individual neurons
Golgi vs Cajal: Golgi supported continued connectivity; Cajal supported discrete neurons

Winner: The nervous system is made of separate cells (Ramón y Cajal)
Key idea: the individual unit of the nervous system is the neuron
Debated for decades; established that neurons are distinct units, not a continuous network

Golgi and Cajal received Nobel recognition for their competing theories
Cajal advocated neuron doctrine; Golgi contested some aspects but made foundational stains possible

Soma (cell body): contains nucleus and cytoplasm
Dendrites: receive signals; dendritic tree; dendritic spines are post-synaptic sites with receptors
Axon: transmits signals; axon hillock (origin of the axon); axon collaterals; axon terminals
Myelin and nodes of Ranvier: speed up conduction; myelinating glia (oligodendrocytes in CNS, Schwann cells in PNS)
Synapse: synaptic cleft between axon terminal and dendrite/spine; presynaptic vesicles and postsynaptic receptors
Different neuronal compartments house distinct molecular machinery (e.g., rough ER absent in axon)

Microtubules (largest): tubulin polymers; transport highways
Neurofilaments (medium): structural support
Microfilaments (smallest): actin; important in dendritic spines
Tau (MAP): stabilizes microtubules; pathological phosphorylation leads to neurofibrillary tangles in disease

Central dogma: DNA → RNA → Protein
Neurons break the simple one-gene–one-protein idea due to high protein demand
Genes expressed in nervous system: roughly
- Approximately 14{,}000 of the 20{,}000 human genes are expressed in developing or mature nervous system
Brain expresses a large fraction of genome proteins: >50 ext{%} of all genome genes

Alternative splicing: introns removed, exons variably included to generate many protein products
Post-translational modification: phosphorylation and other modifications expand protein function
Example: DSCAM gene can generate up to 38{,}016 exon combinations, enabling immense protein diversity
Kinases/phosphatases (e.g., CAMKII) modulate protein activity via phosphorylation

Neurons are energy hogs: ~20 ext{%} of body energy despite only ~2 ext{%} body weight
Mitochondria: up to ~2 imes 10^6 per neuron; sustain ATP, calcium, ROS, and apoptosis signaling
Resting neuron ATP usage: about 4.7 imes 10^9 ATP/s

Macroglia and microglia collectively provide support, insulation, immune defense, and homeostasis
Astrocytes: ~20%; regulate extracellular chemicals, BBB, synapse support, glutamate recycling
Oligodendrocytes: ~25%; CNS myelination; Schwann cells in the PNS perform similar roles
Microglia: ~10%; brain immune cells; remove dead cells and protein aggregates; excessive activity linked to neurodegenerative disease
Precursors: ~5%; contribute to development and maintenance

Myelin sheath speeds up signal conduction along axons
Oligodendrocytes (CNS) and Schwann cells (PNS) form myelin
Node of Ranvier: exposed axonal membrane facilitating saltatory conduction
Myelin-related diseases (e.g., Multiple Sclerosis): autoimmune attack leads to demyelination and impaired signaling

Astrocytes support synapses and regulate neurotransmitter levels (e.g., glutamate → glutamine cycling)
Astrocytes contribute to BBB integrity and nutrient support
Microglia shape synaptic connectivity through pruning and surveillance

Reticular theory suggested a continuous network via gap junctions; however, evidence favored discrete neurons
Some evidence suggests that gap junctions and tunneling nanotubes provide limited direct intercellular exchange, challenging a strict separation
Golgi’s methods revealed important cellular morphology, and Cajal’s work refined understanding of neuronal individuality

Describe basic steps of histological staining and how stains reveal structure
Differentiate Nissl stain vs Golgi stain
Define the Neuron Doctrine and contrast with Reticular Theory
List neuron components and their functions (soma, neurites, axon, dendrites, axon hillock, nodes of Ranvier, synapse, axon terminal, dendritic spines)
Explain cytoskeletal components and how transport moves material inside neurons (anterograde vs retrograde)
Describe immunocytochemistry and its purpose
Identify the three main glial types, their functions, and disease roles
Explain two ways Golgi was not entirely wrong

Neuron Doctrine: neurons are discrete units; not a continuous network
Golgi stain: reveals entire neuron morphology; stains ~1–5% of neurons
Nissl stain: highlights neuronal cell bodies
Astrocyte: glial cell supporting synapses and BBB
Oligodendrocyte: CNS myelination; Schwann cell in PNS
Node of Ranvier: gaps in myelin for saltatory conduction
Dendritic spine: postsynaptic site with receptors
Anterograde transport: soma → axon (kinesins)
Retrograde transport: axon → soma (dyneins)
Central dogma: DNA → RNA → Protein; neurons expand diversity via splicing and PTMs
Tau: microtubule-associated protein; pathological phosphorylation disrupts neurons
Immunocytochemistry: localization of proteins using antibodies
MS: autoimmune demyelination disease