L1 Nervous System Physiology Introduction

Overview

An orienting lecture on the nervous system as the body’s communication and control system. It moves from what the system does and the cells that do it (neurons, their common structure, neural stem cells, glia), through the gross organisation of the CNS by division (cerebrum, diencephalon, brainstem, cerebellum, spinal cord) and the principle that function is localised at both neuronal and regional level, to the structures that protect and support the CNS (bone, meninges and CSF, glial cells, the blood-brain barrier and the cerebral blood supply).

What the nervous system does

Communication and control system with four stated roles:

• Senses the environment and integrates the information.
• Maintains homeostasis (BP, temperature and similar variables).
• Initiates reflex and voluntary actions.
• Thinks, remembers, feels and learns.

Structural facts given: 100,000,000,000 ($10^{11}$) cells; axons connect neurons, sensors and effectors; multiple interconnections; signalling by action potentials and neurotransmitters; peripheral nerves are bundles of axons; glial cells are present throughout.

Peripheral versus central nervous system

Peripheral nervous system

• Lies “outside” the spinal cord.
• Carries afferent sensory input.
• Carries output to effectors, that is muscles and glands.
• Myelinated axons.

Central nervous system (brain and spinal cord)

• Integrates sensory inputs.
• Initiates and coordinates motor outputs.
• Homeostatic functions.
• Higher functions.
• Organised as aggregations of cell bodies (“grey matter”) and myelinated white axons running in tracts.
• Interneurons perform integration; glial cells support and maintain.
• Limited capacity to regenerate.

Neurons

There are $10^{11}$ neurons, each with many synaptic connections, and even more glial cells. All regulation of bodily activity, behaviour, consciousness, perception and memory arises from activity in neural circuits. Mental activity requires an intact brain, but how brain tissue generates subjective experience is posed as an open question. The electrical activity of neurons requires active transport to maintain cellular composition, and at rest about 20% of total metabolism is devoted to supporting brain function.

Neurons are extremely diverse in size and form: a Purkinje cell of cerebellar cortex has a dense, elaborately branched dendritic tree with spines, whereas a pyramidal neuron of neocortex has a single prominent apical dendrite and much simpler branching. Both have a single axon.

Despite that diversity all neurons share the same four components, and each has a distinct function:

Component	Function
Cell body (soma, perikaryon)	Nucleus, gene expression, protein synthesis; “Nissl substance” is free ribosomes
Dendrites	Receive synaptic inputs; chemically gated ion channels
Synapses	Release neurotransmitters; site for neural plasticity
Axon	Conveys action potentials; voltage-gated channels; transports proteins

Structurally these run in sequence: synapses onto dendrites, then the cell body, then the axon hillock leading into the axon, ending at synaptic terminals.

Neural stem cells can multiply and differentiate into neurons or glial cells, but they do not usefully contribute to regeneration after brain damage. The hope is that they might be stimulated, or used as a source of replacement for specific cell groups.

Gross facts about the brain

Average adult brain:

• Weighs 1300 to 1400 grams (3 pounds).
• About 2% of body weight.
• 140 mm wide, 167 mm long, 93 mm high.
• 100,000,000,000 neurons.

Divisions of the CNS

Five divisions: cerebrum, diencephalon, brainstem, cerebellum, spinal cord. On the sagittal section the diencephalon sits deep in the core, with the brainstem below it, the cerebellum posteroinferiorly, the spinal cord continuing below, and the cerebrum surrounding the whole.

Diencephalon

Deep in the core of the brain, comprising:

• Thalamus - relay station to and from the cortex; integrates and processes (sensory) information; roles in pain, attention and alertness.
• Hypothalamus - homeostatic regulation; control of basic activities; the autonomic nervous system; controls the pituitary gland.

Brainstem

Regions: midbrain, pons, medulla. Contains:

• Descending and ascending long tracts.
• Cranial nerves.
• Reticular formation.

Across species (shark, lizard, bird, dog, ape) the cerebrum occupies a progressively larger proportion of the brain relative to brainstem and cerebellum.

Cranial nerves

Twelve pairs. Names, and the functions as given:

No.	Name	Function
I	Olfactory	Smell
II	Optic	Vision
III	Oculomotor	Eye movements
IV	Trochlear	Eye movements
V	Trigeminal	Facial sensation and jaw movements
VI	Abducens	Eye movements
VII	Facial	Facial expression (“smiles and squints”) and taste
VIII	Auditory / vestibular (vestibulocochlear)	Hearing and balance
IX	Glossopharyngeal	Taste and throat sensation; with X, “swallows, speaks and spits”
X	Vagus	Breathing, circulation and digestion
XI	Spinal accessory	Movements of neck and back muscles (“shrugs and shakes”)
XII	Hypoglossal	Tongue movements

Cerebellum

• Balance.
• Posture.
• Coordination.
• Integrates sensory information and corrects for the desired output.

Cerebrum

• Right and left hemispheres.
• Folded surface: gyri and sulci.
• Outer cortex 3 mm thick, the “grey matter”.
• Extensive interconnections.
• Subcortical axonal tracts, the “white matter”.
• Basal ganglia.

Hemispheres are divided into lobes with specific but interrelated functions: frontal, parietal, occipital, temporal. Landmarks are the central fissure (with motor cortex in front of it and somatosensory cortex behind) and the lateral fissure above the temporal lobe. Functions localised on the lateral view: emotion and behaviour, awareness and memory, skilled movements and basic movements in the frontal region; somatosensory cortex and visual recognition parietally; vision occipitally; hearing, smell, balance and muscle coordination, and Wernicke’s speech area around the temporal region; Broca’s speech area anteriorly.

Cerebral organisation also shows:

• “Cross over”: right brain serves the left body, left brain the right body.
• Lateralisation of some functions, with speech in the left hemisphere in over 90% of people.
• Left-brain functions listed: written language, number skills, reasoning, spoken language, scientific thinking, right-hand control. Right-brain functions listed: insight, 3-D forms, art awareness, imagination, left-hand control, music awareness.

Localisation of function

Neuronal level. Different neurons are involved in different tasks, by virtue of their connections and structural specialisations. Death of specific populations produces specific syndromes, for example Huntington’s and Parkinson’s diseases.

Regional level. Neurons concerned with a function tend to group together in specific cortical regions and subcortical nuclei, so damage to specific regions produces specific syndromes, for example a cortical stroke affecting language areas.

Examples of cortical regional specialisation: motor cortex, somatosensory cortex, visual cortex, language areas, and the frontal lobes (executive function). The evidence for this localisation comes from the effects of brain lesions, electrical brain stimulation, recording brain cell activity, and functional imaging. The sensory homunculus maps the body along the sensory strip in order from leg, hip, trunk, neck and head, through shoulder, arm, elbow, forearm, wrist and hand, to the individual fingers and thumb, then eye, nose, face, upper and lower lip, teeth/gums/jaw, tongue, pharynx and intra-abdominal; toes, foot and genitals lie on the medial surface.

Speech control areas

Two areas, Broca’s anteriorly and Wernicke’s posteriorly.

Broca’s

• Motor speech: articulation, rhythm and tone.
• Comprehension intact.
• Also trouble reading and writing.
• Example: prompted with “Ladies and gentlemen you are now invited into the dining room”, the patient produces “…ladies…men…room”.

Wernicke’s

• Comprehension: word selection and ordering.
• Articulation unaffected but meaning corrupted; comprehension impaired.
• Example: asked “Where do you live?”, the patient answers “I came there before here and returned there”.

Other cerebral structures

• Basal ganglia: caudate nucleus (head, body, tail), nucleus accumbens, lentiform nucleus (putamen plus globus pallidus, which has lateral and medial segments), amygdaloid body, terminal stria, thalamus, subthalamic nucleus, substantia nigra.
• Limbic system: learning and emotion.
• Ventricular system: cavities that make CSF.

Protecting and supporting the CNS

Five protective and supporting elements: bones, meninges and CSF, glial cells, blood-brain barrier, blood supply.

Bones. The skull and vertebral column protect the CNS.

Meninges and CSF. Three layers cover and protect the brain: dura mater, arachnoid, pia mater. From the outside in the layers are skin, periosteum, bone, dura mater, arachnoid, pia mater, then grey and white matter. The sub-arachnoid space is filled with CSF, which is made in the ventricles and forms a cushion around brain and cord.

Glial cells

Non-neuronal cells that form the majority of cells and most of the brain mass, and are much more numerous than neurons. Roles in structural support, protection and homeostasis; vital for normal functioning of the brain. They give rise to tumours, for example astrocytoma.

Types:

• CNS: astrocytes (most numerous), oligodendrocytes (myelin), microglia (act like macrophages).
• PNS: Schwann cells.

Astrocytes

• 20% to 50% of the volume of most brain areas.
• Connect to one another by gap junctions, forming a syncytium.
• Surround nodes of Ranvier; ensheath synapses, dendrites and neuronal cell bodies.
• Regulate the flow of small molecules and ions between blood and neurons, provide a structural scaffold, regulate ECF $[K^{+}]$, and metabolise neurotransmitters.
• Processes line the inner surface of the pia mater and the ependyma, and cover the surface of capillaries (the “glia limitans”), with end-feet on capillaries.
• Induce and maintain the tight junctions between endothelial cells, and are involved in angiogenesis.

Oligodendrocytes

• Form myelin in the CNS, one cell sending multiple processes to separate axons.
• Cell surface proteins inhibit axonal regeneration after injury.

Microglia

• Derived from haemopoietic tissue.
• Phagocytose dead tissue and debris.
• Immune response.

Schwann cells

• The only glial cells in the PNS.
• Each Schwann cell myelinates one axon; myelin enhances conduction velocity.
• Also have a role in axon maintenance, releasing factors which promote survival and regeneration.
• Wrapping produces layers of myelin separated by nodes of Ranvier.

Blood-brain barrier

Specialised capillaries control the transfer of substances into and out of the brain. Brain capillaries are joined by tight junctions and have no fenestrations. This helps isolate the brain from the body and maintain a constant composition of the fluid bathing brain cells. It limits, but does not prevent, blood/CSF exchange.

Selectivity at the endothelial cell, in order of ease of passage:

1. Lipid-soluble substances, for example alcohol, penetrate the barrier and cross freely.
2. Glucose and amino acids require transport proteins.
3. $N{a}^{+}$ and $K^{+}$ require ion channels.
4. Plasma proteins are excluded.

Cerebral blood supply

• A constant supply is needed: 750 ml/min.
• Four major arteries, with defined “territories”.
• Changes in blood flow cause changes in cerebral function, either transient or irreversible.
• Venous drainage is via the dural sinuses.

Warning

Several slides in this deck carry transcript flags: slide 15 is an unlabelled brain photograph with no stated purpose, slides 41/42 and 46/51 are duplicated content, and the small source-URL and figure-citation captions on slides 36, 37, 57 and 60 were not legible.

Self-test

1. List the four functions of the nervous system as a communication and control system.
2. Distinguish the peripheral from the central nervous system in terms of location and the direction of traffic each carries.
3. What proportion of total resting metabolism is devoted to supporting brain function, and why is that requirement so high?
4. Name the four common components of a neuron and give the function of each.
5. Distinguish a Purkinje cell of cerebellar cortex from a pyramidal neuron of neocortex.
6. Why do neural stem cells not solve the problem of recovery after brain damage?
7. State the average adult brain weight and its proportion of body weight.
8. List the five divisions of the CNS.
9. Distinguish the functions of the thalamus from those of the hypothalamus.
10. List the three regions of the brainstem and the three things the brainstem contains.
11. Which cranial nerves move the eyes, and which two act together in swallowing and speech?
12. List the functions of the cerebellum.
13. Describe the layered organisation of the cerebrum from the surface inwards.
14. What does “cross over” mean for cerebral control, and how lateralised is speech?
15. Distinguish localisation of function at the neuronal level from localisation at the regional level, with an example of each.
16. List the four kinds of evidence used to establish cortical regional specialisation.
17. Distinguish Broca’s from Wernicke’s aphasia by fluency, comprehension and the character of the speech produced.
18. A patient is asked where they live and replies “I came there before here and returned there”, with normal articulation. Which area is damaged, and what is the deficit?
19. List the three meningeal layers from outside in, and say where CSF sits and where it is made.
20. Distinguish the four glial cell types by location and function.
21. List four regulatory roles of astrocytes.
22. Why does myelin damage in the CNS carry a worse prognosis for axonal regrowth than damage in the PNS?
23. Describe how the blood-brain barrier is constructed and predict how alcohol, glucose, potassium and plasma protein each cross it.
24. State the cerebral blood flow requirement and the number of major arterial territories.
25. Integrative: a stroke in one arterial territory of the left hemisphere leaves a patient with right-sided weakness and non-fluent speech with preserved comprehension. Using localisation, lateralisation and the crossed organisation of the cerebrum, explain each finding.

Answers

Reveal answers

1. Senses the environment and integrates information; maintains homeostasis (BP, temperature); initiates reflex and voluntary actions; thinks, remembers, feels and learns.
2. The PNS lies outside the spinal cord and carries afferent sensory input in and output to effectors (muscles and glands) out, with myelinated axons. The CNS is brain and spinal cord, and integrates sensory input, initiates and coordinates motor output, performs homeostatic and higher functions.
3. About 20% at rest. The electrical activity of neurons requires active transport to maintain cellular composition.
4. Cell body (soma/perikaryon): nucleus, gene expression, protein synthesis, with Nissl substance being free ribosomes. Dendrites: receive synaptic inputs, chemically gated ion channels. Synapses: release neurotransmitters, site of neural plasticity. Axon: conveys action potentials, voltage-gated channels, protein transport.
5. The Purkinje cell has a dense, elaborately branched dendritic tree bearing spines; the pyramidal neuron has a single prominent apical dendrite and a much simpler branching pattern. Both have one axon.
6. They can multiply and differentiate into neurons or glial cells, but do not usefully contribute to regeneration after brain damage; the hope is that they could be stimulated or used as a replacement source for specific cell groups.
7. 1300 to 1400 g (3 pounds), about 2% of body weight.
8. Cerebrum, diencephalon, brainstem, cerebellum, spinal cord.
9. Thalamus: relay station to and from cortex, integrates and processes sensory information, pain, attention and alertness. Hypothalamus: homeostatic regulation, control of basic activities, the autonomic nervous system, control of the pituitary gland.
10. Midbrain, pons, medulla. It contains descending and ascending long tracts, cranial nerves, and the reticular formation.
11. Eye movements: oculomotor (III), trochlear (IV) and abducens (VI). Glossopharyngeal (IX) and vagus (X) together for swallowing, speaking and spitting.
12. Balance, posture, coordination, and integrating sensory information to correct for the desired output.
13. An outer folded cortex of grey matter about 3 mm thick, thrown into gyri and sulci, with extensive interconnections; beneath it subcortical axonal tracts of white matter; and deeper still the basal ganglia. It is divided into right and left hemispheres.
14. The right brain serves the left side of the body and the left brain the right side. Speech is in the left hemisphere in over 90% of people.
15. Neuronal level: different neurons perform different tasks by their connections and structural specialisations, so death of a specific population gives a specific syndrome, for example Huntington’s or Parkinson’s disease. Regional level: neurons for a function group into specific cortical regions and subcortical nuclei, so regional damage gives a specific syndrome, for example a cortical stroke affecting language areas.
16. Effects of brain lesions, electrical brain stimulation, recording brain cell activity, and functional imaging.
17. Broca’s is a motor speech deficit affecting articulation, rhythm and tone, producing fragmentary output (“…ladies…men…room”) with intact comprehension but also trouble reading and writing. Wernicke’s affects comprehension, word selection and ordering: articulation is unaffected but meaning is corrupted and comprehension is impaired.
18. Wernicke’s area. Comprehension, word selection and ordering are impaired, so meaning is corrupted while articulation remains normal.
19. Dura mater, arachnoid, pia mater. CSF fills the sub-arachnoid space and is made in the ventricles, forming a cushion around brain and cord.
20. Astrocytes (CNS, most numerous): structural scaffold, regulation of the environment and of the blood-brain barrier. Oligodendrocytes (CNS): form myelin. Microglia (CNS): act like macrophages, phagocytosis and immune response. Schwann cells (PNS only): myelinate one axon each and support axon maintenance.
21. Regulate the flow of small molecules and ions between blood and neurons; provide a structural scaffold; regulate ECF potassium concentration; metabolise neurotransmitters. They also induce and maintain endothelial tight junctions and take part in angiogenesis.
22. In the CNS oligodendrocytes carry cell surface proteins that inhibit axonal regeneration after injury, and the CNS has only a limited capacity to regenerate. In the PNS Schwann cells release factors that promote axon survival and regeneration.
23. Brain capillaries are specialised: endothelial cells joined by tight junctions with no fenestrations, induced and maintained by astrocytes whose processes cover the capillary surface. Alcohol is lipid soluble and crosses freely; glucose and amino acids need transport proteins; sodium and potassium need ion channels; plasma protein is excluded. The barrier limits rather than prevents exchange.
24. 750 ml/min, supplied by four major arteries with defined territories; venous drainage is via the dural sinuses.
25. The lesion is in the left hemisphere. Because motor control crosses over, left-hemisphere damage weakens the right side of the body. Because speech is lateralised to the left hemisphere in over 90% of people, a left-sided lesion is the one that causes aphasia. Non-fluent speech with preserved comprehension localises within that hemisphere to Broca’s area, a motor speech deficit of articulation, rhythm and tone rather than of comprehension. That the deficits appear together reflects the arterial territory: one of the four major arteries supplies a defined region containing both, and changes in its blood flow change function in that region, transiently or irreversibly.