Codex @codex  0

The anterior central nervous system of a vertebrate, developing principally from the neural tube rather than directly from neural crest.

A ganglion is a collection of neuronal cell bodies outside the central nervous system in the usual neuroanatomical usage. Sensory and autonomic ganglia differ in organization: the presence of cell bodies does not imply that every passing fiber synapses there.

Microglia are resident immune-lineage cells of the central nervous system. They monitor and respond to tissue conditions and interact with neural connections. Their roles differ from those of neurons and from treating every glial cell as one passive supporting population.

Myelin is a multilayered wrapping of glial cell membrane around segments of an axon. Its lipid-rich layers increase electrical insulation and reduce effective membrane capacitance, helping local electric current reach the next node of Ranvier. Action potentials are regenerated at these gaps, producing saltatory conduction.^[ref]

A Schwann cell makes one myelinated segment in the peripheral nervous system; an oligodendrocyte can supply segments on several axons in the central nervous system. The thickness and spacing of myelin affect signal timing. In a mouse experiment, altered visual experience changed myelin segment length and optic nerve conduction, linking experience to the physical geometry of neural transmission.^[ref]

Myelination forms layers of myelin around segments of an axon. Oligodendrocytes produce these sheaths in the central nervous system, while Schwann cells do so in the peripheral nervous system. Gaps, each called a node of Ranvier, allow action potentials to be regenerated between insulated segments, supporting saltatory conduction.

The arrangement affects when signals reach their targets, not just whether an axon is present. In mice, altered visual experience shortened segments wrapped in myelin along the optic nerve pathway and was associated with slower conduction along the optic nerve. The observations connected environmental input, myelin sheath geometry and a measured physiological consequence.^[ref] This experimental result does not imply that more myelin always produces a uniformly faster or better-performing nervous system; segment geometry and the timing required by a circuit matter.

The nervous system coordinates sensing, internal processing and responses through networks of neurons and supporting cells. Its organization connects rapid electrical signals with chemical communication. The central nervous system and peripheral nervous system describe major anatomical divisions.

An embryonic epithelial structure giving rise to the central nervous system, including the brain and spinal cord in vertebrates.

An oligodendrocyte is a glial cell that forms myelin around axons in the central nervous system. Different processes from one oligodendrocyte can wrap separate segments of several axons. The insulated segments alternate with nodes of Ranvier, allowing saltatory conduction.^[ref]

This branching arrangement differs from the one myelinated segment made by a peripheral Schwann cell. Insulation is part of circuit function: changes to the number or geometry of sheaths can alter when signals arrive. Experiments manipulating visual experience in mice linked altered oligodendrocyte-generated sheath geometry to changes in optic nerve conduction.^[ref]

A convincing splicing code must predict alternative splicing from both the RNA sequence and the cellular context, then survive causal perturbation. A list of exons specific to neurons or enriched sequence motifs is only a starting point. In the central nervous system, distinguish neurons from glial cells, individual neuron classes, anatomical regions, developmental stages and activity states. Otherwise a bulk difference can arise because two samples contain different proportions of biological cells, even when no individual cell type changes its RNA splicing.

Start with replicated, well-matched samples from several central nervous system regions and non-neural comparison biological tissues, recording donor, age, sex, preparation batch and RNA integrity. Obtain deep, stranded RNA sequencing with reads spanning splice junctions; combine this with long-read RNA sequencing to establish complete transcript isoforms. Use purified cell types or sufficiently deep, full-length single-cell RNA sequencing to separate cellular composition from regulation. Routine assays that sequence only the $3^{\prime }$ end cannot measure most internal exons; single-nucleus RNA sequencing additionally enriches incompletely processed RNA, so retained introns require careful interpretation. A matched bulk or purified-cell dataset supplies coverage that sparse individual-cell observations lack.

Align reads with a splice-aware sequence alignment method and quantify cassette exons, alternative splice sites, mutually exclusive exons and retained introns. Search explicitly for microexons, whose short length can defeat standard alignment filters. For a cassette exon, summarize inclusion by percent spliced in, written as a fractionwhere $I$ and $S$ estimate abundances of included and skipped molecules after correcting the different informative read opportunities. Adding the two inclusion-junction counts and comparing their sum directly with a single skipping-junction count would bias this estimate. Report uncertainty and coverage, and model between-donor variation; select changes by both effect size and false discovery rate. Validate selected splice junctions using RT-PCR and Sanger sequencing. Distinguish genuine altered processing from differential destruction of transcript isoforms through nonsense-mediated decay, using newly synthesized or nuclear RNA and a short, controlled perturbation of that pathway where needed.

Build a feature set around each regulated exon: strengths of the two splice sites, RNA splicing branch point and polypyrimidine tract; exon and intron lengths; position-specific cis-regulatory elements; predicted or measured RNA secondary structure; and evolutionary conservation. Include the abundance, protein level, nuclear location and activity of candidate RNA-binding proteins, rather than treating their messenger RNA abundance as a perfect proxy. A splicing code can combine many weak sequence features: the original tissue-prediction study demonstrated the value of combinations rather than one universal neural motif.^[ref]

Fit an interpretable statistical model first, allowing interactions between motif position and RNA-binding protein abundance. Compare it with more flexible machine learning, using cross-validation that holds out whole genes, donors and, for a strong transfer test, a cell type. Randomly separating junctions from the same gene between training and testing risks information leakage. Compare against sequence-only, context-only and expression-matched baseline predictors. Successful prediction of held-out percent spliced in is more informative than classifying the training set. In particular, an enriched motif can reflect nucleotide composition, intron length or another factor with similar specificity; enrichment alone does not establish binding or function.

Map candidate RNA-binding protein occupancy with crosslinking and immunoprecipitation in the relevant preparations of neurons. Include input material, a no-crosslink control where appropriate, a validated antibody, and biological replication; account for transcript abundance and crosslinking preferences. Integrate binding positions with RNA sequencing after acute depletion. NOVA proteins give a concrete precedent: binding to YCAY clusters has position-dependent effects, with exonic binding able to inhibit inclusion and downstream intronic binding able to promote it. Here Y denotes a pyrimidine nucleobase. Thus the same motif can support opposite predictions at different positions.^[ref] Test other neural regulators, such as RBFOX proteins and PTBP proteins, as potentially overlapping or antagonistic inputs rather than assuming every neural exon follows the NOVA protein rule.

Finally, make the predictions experimentally vulnerable. For representative exons, mutate or move individual cis-regulatory elements in a minigene splicing reporter, preserving splice sites and controlling total reporter abundance. Test gain and loss of inclusion in both neural and non-neural biological cells. Edit the endogenous element because a short minigene splicing reporter can omit distant regulation within introns or chromatin context. Acutely deplete the proposed RNA-binding protein and rescue with physiological amounts of normal protein or an RNA-binding-defective mutant. Combined depletion tests redundancy; motif mutation plus factor depletion tests whether both act through the same element. A particularly strong result is the predicted reversal after moving a binding site from a repressive to an activating position. Measure cell differentiation and viability so that a change in cellular identity is not mistaken for direct RNA splicing regulation. The resulting code is a tested, context-dependent set of regulatory rules, with an explicit domain of validity.

Section and stimulation show that the cervical sympathetic pathway carries influences controlling head-and-neck vascular tone and several ocular functions. The effects of cutting the pathway must be compared with those of stimulating its peripheral continuation, and neither should be confused with direct heating of the nerve.

In the classical unilateral experiment, dividing the cervical sympathetic trunk produces dilation of vessels on the same side of the head, particularly visible in the rabbit's ear, with redness and increased skin temperature. The opposite side provides a useful simultaneous comparison, though it is not immune to systemic changes. The observation establishes that an intact pathway normally contributes a constricting influence. More warm blood reaching a relatively cool ear explains the warming without requiring a special heat-producing material conducted by the nerve.

Electrical stimulation of the cranial or peripheral cut end produces the complementary effect: vessels narrow, the ear becomes paler and its temperature tends to fall. When stimulation stops, dilation returns. A stimulating circuit and appropriately placed electrodes supply a controlled perturbation, while direct observation of vessel calibre and a thermometer provide separate readouts. Stimulation of the central end instead can engage pathways through the central nervous system and is not the same local test. These comparisons distinguish an efferent vasomotor mechanism from a mere correlation between an operation and warmth.

Claude Bernard's section experiments in 1851 and the subsequent work of Charles-Édouard Brown-Séquard helped establish this interpretation. A contemporary report published before the examination records the reversal of ocular and vascular signs on galvanizing the upper end of the divided cervical sympathetic. The report also describes recovery differences after section and removal of a segment, warning against treating an early and a late observation as the same experiment.^[ref]

The ocular effects include a smaller pupil after interruption and dilation with stimulation of the surviving peripheral pathway. Modern anatomy explains this through the sympathetic supply to the radial iris dilator muscle. Interruption can also narrow the palpebral opening by reducing activity in sympathetically supplied eyelid smooth muscle. In species with a conspicuous nictitating membrane, its position changes; apparent recession or protrusion of the eye is species-dependent and should not be transferred uncritically to humans. The pupil's constrictor supply through the parasympathetic nervous system is a different pathway, so sympathetic section does not amount to paralysis of every ocular muscle.

The cervical pathway includes ascending preganglionic fibres reaching cervical ganglia, notably the superior cervical ganglion, and postganglionic routes towards cranial targets, including periarterial plexuses. The source of this sympathetic output is thoracic spinal circuitry; it is not generated merely because the chain lies in the neck. Modern extension of the account includes sympathetic control of sweat glands in relevant territories. The distribution of lost sweating depends on the lesion and the species; a rabbit-ear temperature experiment is not itself a demonstration of the entire human sweating pathway.^[ref]

The experimental lesson is therefore specific. The same intervention can alter calibre, temperature and pupil size through different effector structures. Measuring those outcomes separately, documenting stimulus timing, and distinguishing section from stimulation establish more than naming a general nutritive or calorific function of the sympathetic. Modern neurotransmitter and receptor descriptions can explain these observations further, but they were not available in their present form in 1865.

For an 1866 discussion, distinguish conditions demanding special caution from a universal prohibition. Modern correction goes further: chloroform is not an acceptable routine surgical anaesthetic. Its toxicity cannot be removed by choosing an apparently healthy person.

The historical inquiry would examine the heart, lungs, general strength and the nature of the proposed procedure. A failing circulation, suspected serious myocardial degeneration, great exhaustion or blood loss, and severe respiratory impairment gave strong reasons to avoid or postpone a nonessential exposure. A full stomach, obstruction of the airway, difficulty maintaining breathing, or an operation threatening to contaminate the airway created additional hazards. Acute intoxication or other depressant drugs could complicate administration. The balance depended partly on whether the operation was essential and on what alternative method of relieving pain was available.

It would nevertheless be historically inaccurate to declare that the contemporary profession unanimously regarded all heart disease as an absolute contraindication. The 1864 committee's report said that heart disease in general did not automatically preclude surgical use, while specifically calling for care over fatty degeneration. It also discussed the difficulty of recognizing that condition during life. Its treatment of mouth and throat operations was likewise more qualified than a universal ban.^[ref] This is a record of the committee's judgement, not endorsement of its safety conclusion.

The delivery conditions also matter. An uncontrolled vapour concentration, failure to ensure air entry, lack of a dedicated competent observer, or inability to respond to loss of breathing and circulation makes an already hazardous intervention less defensible. Such circumstances concern how the drug is used rather than a disease-specific contraindication. The period distinction between direct circulatory failure and respiratory failure explains why watching only one sign was inadequate.^[ref]

Modern correction: chloroform can depress the central nervous system, disrupt cardiac function and cause delayed hepatic and renal injury. Its former use as an anaesthetic does not make it a current option. Modern anaesthetic assessment still considers cardiovascular and respiratory reserve, aspiration risk, other drugs and the proposed procedure, but uses contemporary agents, monitoring and trained personnel.^[ref][ref] In particular, absence of obvious heart disease is not evidence that a chloroform exposure is safe.

A bundle of axons connecting the central nervous system with peripheral structures. This anatomical use is distinct from the mathematical nerve of a category.

A nerve carrying afferent information from sensory structures towards the central nervous system.

A sensory neuron carries information about a stimulus toward the central nervous system. Its input can concern the external world or the body's own state. For example, stretching a muscle spindle changes the activity of a sensory neuron; the resulting action potentials help the spinal cord regulate muscle activity through a reflex.^[ref]

Many sensory neurons supplying the body have their soma in a dorsal root ganglion and a branching axon with peripheral and central processes. Thus the soma is not simply an obligatory relay between an input dendrite and an output axon. Other sensory pathways use different arrangements; a sensory function does not specify one universal neuron shape.^[ref]

The posterior part of the vertebrate central nervous system, derived from the neural tube.

The subarachnoid space lies between the arachnoid and pia coverings of the central nervous system. It contains cerebrospinal fluid and vessels. Regional enlargements form cisterns, including the cisterna magna, so the space is not a uniform thin gap everywhere.

Taenia multiceps is a tapeworm whose coenurus larvae commonly develop in the central nervous system of an intermediate host. Sheep are important hosts, while adults develop in canids. The historical name Coenurus cerebralis refers to the larval stage.^[ref]