Neurons - Chpt. 2

Structure: highly polarized; Cytoskeleton supports diverse forms; the structure determines function.
Central dogma challenge: brain requires protein diversity beyond gene count; neurons “hate” the simple DNA→RNA→protein path.
Energy demand: neurons are energy hogs; use ~ $20\%$ of body energy with only ~ $2\%$ body weight; mitochondria demand is very high (up to $2 \times 10^6$ per neuron).
Non-replication: most neurons do not get replaced; the neurons you are born with are the neurons you die with (small progenitor pools exist).
Proteome complexity: neurons maximize diversity with limited genetic diversity.

Soma (cell body) contains nucleus; neurites extend from it.
Dendrites: input branches; receive signals from other neurons.
Axon: output fiber; transmits signals to other neurons, muscles, or targets.
Axon hillock: start of the axon; initiation site for action potentials.
Axon terminals: synaptic output sites; vesicles with neurotransmitter.
Myelin: insulating layer around axons; speeds conduction.
Nodes of Ranvier: gaps in myelin for saltatory conduction.
Schwann cells (PNS) and oligodendrocytes (CNS): form myelin.
Dendritic spines: postsynaptic sites on dendrites; contain receptors; highly dynamic.

Dendrites are typically post-synaptic; dendritic spines provide specialized receptor-rich sites.
Dendritic spine density relates to synaptic strength and plasticity; alterations linked to disorders (e.g., autism).

Axon transmits signals; axon terminals form presynaptic components of synapses.
Axon contains many mitochondria; rough ER is absent in axons.
Synapse: presynaptic axon terminal with vesicles; postsynaptic dendritic spine with receptors; synaptic cleft separates pre- and postsynaptic sides.

Microtubules (largest): built from tubulin; regulated by microtubule-associated proteins (MAPs).
Neurofilaments (medium): provide structural support.
Microfilaments (smallest): important in dendritic spines and neurites.
Anterograde transport: away from soma (kinesins).
Retrograde transport: toward soma (dyneins).
Transport delivers proteins and organelles to neurites; essential for neuron function.

Tau is a microtubule-associated protein (MAP) that stabilizes microtubules.
In Alzheimer's disease, kinases phosphorylate tau abnormally; phosphorylated tau dissociates from microtubules and forms neurofibrillary tangles, leading to microtubule collapse and neuron death.

Gene counts: ~ $2.2 \times 10^4$ protein-coding genes; nervous system expresses ≈ $1.4 \times 10^4$ of them; brain expresses >50% of all genes.
How diversity arises:
- Alternative splicing: introns removed, exons shuffled; DSCAM can have up to ~ $3.8016 \times 10^4$ exon combinations, enabling vast diversity.
- Post-translational modification (e.g., phosphorylation): kinases add phosphate groups; CAMKII is a brain kinase important for learning.
- RNA editing and alternative promoters also contribute.
Proteome complexity: from ~ $2.0 \times 10^4$ genes to > $10^6$ proteins; transcriptome around $1.0 \times 10^5$ transcripts.

Neurons consume ~ $20\%$ of body energy despite ~ $2\%$ body weight.
Mitochondria: up to $2 \times 10^6$ per neuron; ATP production sustains membrane potential and synaptic transmission.
Resting ATP usage: ~ $4.7 \times 10^9$ ATP/s per neuron.

Three main glia types: astrocytes, oligodendrocytes, microglia; plus precursors and other glia.
Astrocytes:
- Support synapses; regulate extracellular chemicals (e.g., glutamate) by uptake and conversion to glutamine.
- Regulate the blood–brain barrier (BBB).
Oligodendrocytes (CNS) / Schwann cells (PNS): myelinate axons; form nodes of Ranvier; high-speed signaling.
Microglia: resident immune cells; remove dead cells and prune synapses; participate in injury response and inflammation.

Myelin speeds signal conduction; nodes of Ranvier enable saltatory conduction.
Multiple Sclerosis: autoimmune attack on myelinating cells; demyelination slows or blocks signaling.

Reticular theory (Golgi): brain is a continuous network.
Neuron doctrine (Cajal): neurons are discrete cells separated by synapses; function via synaptic communication.
Reality: most brain cells are separate, but there are gap junctions and tunneling nanotubes that enable direct cell-to-cell exchange in some contexts.

Tool to locate proteins in cells using antibodies.
Visualizes protein distribution with light microscopy; helps map protein localization and cell type markers.

Neuron structure-function relationship is central to understanding signaling.
Unique neuron features arise from cytoskeletal organization, energy demands, and proteome diversification beyond gene count.
Neuronal signaling depends on axonal transport, synapses, and myelination.
Glial cells play essential supportive and regulatory roles in neural function and disease.
Classical theories (Golgi vs Cajal) have evolved with evidence of discrete neurons but also intercellular connectivity.

Soma, dendrites, axon, axon hillock, axon terminal, dendritic spines, nodes of Ranvier, myelin, oligodendrocyte, Schwann cell, astrocyte, microglia.
MAPs, Tau, microtubules, neurofilaments, microfilaments, kinesin, dynein.
Gap junctions, tunneling nanotubes.
Immunocytochemistry (ICC).
DSCAM, alternative splicing, post-translational modification, phosphorylation.