Nervous System

Question 1

What are the 2 systems controlling homeostasis?

Answer 1

Endocrine and nervous.
Both sense changes (input signal) and generate responses to them (output signals).

Question 2

What are the key differences between nervous and endocrine systems?

Answer 2

Nervous:
- directly contacts targets through innervation
- uses both electrical (action potential) and chemical signals (neurotransmitters)
- very specific targeting and amount of it

Endocrine:
- contacts targets through blood
- uses chemical signals only (hormones)
- less specific in targeting and amount

Question 3

What is the difference between neurohormones, neurotransmitters and normal hormones?

Answer 3

Normal hormones:
- produced and secreted by endocrine (epithelial tissues)
- released in blood to reach distant targets

Neurotransmitters:
- produced and secreted by neurons
- released in synaptic cleft to reach the post-synaptic neuron (or another cell like muscle fibre etc) from a pre-synaptic neuron

Neurohormones:
- produced and secreted by neurons
- released in blood to reach distant targets

Question 4

What is nervous system organisation?

Answer 4

Central nervous system (membrane called meninges protects both):
- brain (inside cranium)
- spinal cord (in vertebral column, dorsal side; also protected with cerebrospinal fluid)

Peripheral nervous system:
- cranial nerves (extend from brain)
- spinal nerves (extend from spinal cord)
- ganglia (a group of neuron cell bodies, “knots” outside CNS)

Question 5

What are the 3 key types of neurons?

Answer 5

1) Sensory (afferent neurons): carry information from sensory organs into CNS.

2) Interneurons (interconnecting neurons): receive signals from sensory neurons; integrating systems in CNS, the network of highly branched neurons; send signals to efferent neurons.

3) efferent neurons: send signals from CNS to tissues/organs, which results in response (movement, hormone release etc):
- somatic motor neurons to skeletal muscles for voluntary movement;
- autonomic neurons to smooth muscles (lungs, digestive tract, bladder etc) and cardiac muscle to MODIFY the rate of reflectory/spontaneous contraction.
a) parasympathetic in calm state - increase homeostasis, stabile values (slower heart rate, bronchial contraction, release of urine)
b) sympathetic in stress - increase values (increased heart rate, bronchial dilation, increased blood pressure through renin)

But it is other way round in digestive system: parasympathetic (more secretion, more motility), sympathetic (less secretion and less motility)

Question 6

What is the typical structure of motor neuron?

Answer 6

• dendrites (short extensions with spikes and knobs to further increase their surface area), take input signals. Often much, much more branched and “tree-like” than linear axons, it varies on neuron type (Purkinje neurons have more branched dendrites than pyramidal neurons).
• cell body with nucleus, integration centre (1/10 or less of the total cell volume)
• axon hillock
• axon (long extensions), release output signals, contacts the next dendrite with axon terminal and synapse. Full of cytoskeleton, lacks ribosomes and endoplasmic reticulum, receives proteins from axon body
• myelin sheath surrounds axon (except at nodes of Ranvier) to increase the speed of an output signal through saltatory conduction

Question 7

Are there electrical synapses (with no neurotransmitters diffused through synaptic cleft)?

Answer 7

Yes, it is when pre-synaptic and post-synaptic cells are connected with gap junctions - this communication if faster and bidirectional (chemical synapsis is one-directional).

Question 8

What are the 2 main categories of nervous tissue?

Answer 8

• Neurons (100 billion in human brain)
• Glia: assist, support, feed and protect neurons, there are 10-50 times more of them than neurons

Question 9

What are the 6 main types of glial cells?

Answer 9

In CNS:
1) Ependymal cells: barriers between compartments (brain ventricles, choroid plexus, non-nervous organs), source of neural stem cells, sweep cerebrospinal fluid. Columnar and ciliated.

2) Astrocytes: connected to blood brain barrier, provide fuels, absorb K+, water and neurotransmitters; secrete neurotrophic factors (to stimulate neuron growth, differentiation and development); also a source of neural stem cells. Highly branched with mushroom-like knobs.

3) Microglia: modified macrophages (immune function: phagocytosis, antigen presentation, release of cytokines). Moderately branched with spikes.

4) Oligodendrocytes: one cell forms myelin sheath around several interneurons. Shape: normal cell body with multiple cylinders attached.

In PNS:
5) Schwann cells: ~500 cells form myelin sheath around single axon; also secretes neurotrophic factors. Shape: concentrated layers of cell membrane in cylinder, each cell is 1.0-1.5 mm wide.

6) Satellite cells: support cell bodies, regulate chemical environment; found in ganglia. Slightly branched.

Question 10

What are the 4 principles of electricity in physiology?

Answer 10

1) the net amount of electrical charge is always 0; body is always neutral as a whole.

2) opposite charges attract and the same repel.

3) separating charges requires energy.

4) if charges can move through the substance, it is conductor; otherwise it is an insulator.

Question 11

What is membrane potential?

Answer 11

In all cells, there is always voltage difference at extracellular and intracellular sides of membrane due to different/uneven ion concentrations on the corresponding sides (Na+ and Cl- are mostly outside; K+ and other anions are mostly inside).

Most of the cells do not change their membrane potentials (it is always resting).

At rest, outside is slightly more positive than outside.

Some cells (neural, muscle etc) actively change their membrane potentials as a response to a chemical or mechanical stimuli (excitable cells).

Question 12

On what does membrane potential depend?

Answer 12

• electrochemical gradient
• membrane permeability (if membrane is permeable to everything, voltage would be 0; selective permeability creates membrane potential)

Question 13

What does limit the permeable ions from completely leaving one side?

Answer 13

When ions leaves one side, the side it left becomes more and more oppositely charged, which attracts some of those permeable ions back.

Question 14

What is a key leak channel/pumps which maintains membrane potential?

Answer 14

Na+/K+ channels/pumps are present in every cell; 3 Na+ are transported outside and 2 K+ are transported inside.

Pump uses ATP, channel does not.

Most cells are 40X more permeable to K+ than Na+.

Question 15

What is equilibrium potential?

Answer 15

Chemical (concentration gradient) and electrical (movement to the opposite charge) forces balancing each other out.

Calculated with the Nernst equation (for one ion) and Goldman-Hodgkin-Katz equation (for multiple ions).

Nernst equation (result is normally in mV):
E = (61 / charge) * log(ion concentration in ECF / ion concentration in ICF)

Question 16

How the membrane potential can be measured?

Answer 16

Using voltmeter: placing one electrode at ECF (often this is a saline bath) and another electrode at ICF (inside cell).

Absolute values (for example, +1 mV and -1 mV) are converted to relative by assuming that ECF has 0 mV (so, for example, ICF becomes -2 mV).

Membrane potential may change in some cells, resulting in graphs.
- voltage goes down: hyperpolarisation
- voltage goes up: depolarisation

Question 17

What is multiple sclerosis?

Answer 17

Damage of myelin sheath in central nervous system, resulting in weakness, numbness, tingling, visual disturbances, muscle spasms, pain, cognitive decline, speech and swallowing problems etc.

Could be caused by herpes (Epstain-Barr virus), but not directly but because it somehow triggers autoimmune attack of the part of oligodendrocytes surrounding axons.

Question 18

What are the 3 main types of channels?

Answer 18

• Chemically gated (binding of certain substance such as neurotransmitter opens or closes them);
• Mechanically gated (open due to stretch or vibration);
• Voltage-gated (open and close when membrane potential reaches certain value due to depolarisation)

All of them are usually permeable to a single type of ion, such as Na+.

Question 19

What are the 4 main types of ions channels in neurons?

Answer 19

Ion channels for Na+, K+, Ca2+ and Cl-

Changes in K+ permeability have the biggest effect on membrane potential.

Question 20

What are channelopathies?

Answer 20

Malfunctioning channels due to mutations and incorrect folding. Example - cystic fibrosis.

Question 21

What are action potentials?

Answer 21

Changes in membrane potential that do not fade (do not lose their strength) - they form nerve impulses. Generated at axon hillock and propagate through axon to axon terminal; in synaptic cleft, membrane potential is carried with synaptic transmission (with neurotransmitters).

Question 22

What 3 factors determine neuron’s resistance to propagate action potential through current flow?

Answer 22

• amount of channels at cell membrane: more channels, less resistance
• cytoplasm composition: less different solutes, less resistance
• cell (axon/dendrite) diameter: the bigger diameter, the smaller resistance

Question 23

What are the graded potentials?

Answer 23

Various electric signals travelling across neuron which fade up due to membrane resistance and leak channels.

They can sum up and if the summing becomes strong enough, may trigger an actual action potential at the Na+-voltage-gated-channels-rich trigger zones.

Question 24

What are the types of graded potentials?

Answer 24

• excitatory (leading to depolarisation); if strong enough to trigger action potential, become suprathreshold
• inhibitory (leading to hyperpolarisation)

Question 25

Is there a specific membrane potential value that may cause action potential or is there a range (in nervous system)?

Answer 25

There is a specific value, -50 mV: all-or-none event. Anything below -50 mV just stays as graded potential, but reaching just -50 mV is enough to cause action potential.

Question 26

What are the stages of action potential in neurone?

Answer 26

1) Resting membrane potential at -70 mV 2) Depolarising stimulus (slow Na+ entry) increases voltage until it reaches -50 mV (a threshold) 3) Voltage-gated Na+ and K+ channels open 4) Depolarisation: rapid Na+ entrance from ECF to cytoplasm leads to the maximal voltage of +30 mV 5) At +30 mV, Na+ channels close and K+ channels open 6) Repolarisation: rapid (but slightly less rapid than for Na+) K+ release from cytoplasm to extracellular fluid leads to minimal voltage of -80 mV; -80 mV < -70, means hyperpolarisation happened. 7) At -75 mV, K+ channels close and -70 mV is reached back. 8) original ion concentrations at ECF and ICF are restored with sodium-potassium pump.

Question 27

What is the purpose of hyperpolarisation?

Answer 27

Does not allow new action potentials to appear too early and prevents backflow conduction.

Question 28

Is there only one action potential per neurone?

Answer 28

No, there are multiple action potentials per neurone: a domino effect - one action potential triggers the next in the adjacent region until the synaptic cleft is reached.

Question 29

What are synapses?

Answer 29

Sites of neuron-to-neuron (or muscle fiber or some other cells) communication. Electrical signal is transferred from one neuron to next with neurotransmitters. One neuron may have 10 000-150 000 synapses.

Question 30

What types of signals are neurotransmitters and neuromodulators?

Answer 30

They are paracrine (acting at small distances only) or even autocrine signals (activating the cell they were released from).

Question 31

What are the differences between neurotransmitters and neuromodulators?

Answer 31

Neurotransmitters: - fast response (few milliseconds), lasts for short time - bind to chemically gated ion channels - if more Na+ comes inside, excitatory depolarisation in the post-synaptic cell (signal becomes stronger) - if more K+ comes out or more Cl- in, inhibitory hyperpolarisation in the post synaptic cell (signal becomes weaker) Neuromodulators: - slow response (seconds to minutes), lasts for long time - bind to G protein-coupled receptor - G protein activates second messenger pathway - this regulates permeability of ion channels, leading to the results analogous in neurotransmitters - also leads to modification or synthesis of new proteins for many other regulatory purposes

Question 32

What are the main neurotransmitters?

Answer 32

1) Acetyl choline at cholinergic neurons to nicotinic cholinergic receptors (at preganglionic neurons) or muscarinic cholinergic receptors (at parasympathetic postganglionic neurons). 2) Noradrenalin at adrenergic neurons to adrenergic receptors (at sympathetic postganglionic neurons). - alpha adrenergic receptors at blood vessels muscle - beta adrenergic receptors at cardiac muscle Both are in autonomous nervous system. Other important ones are glutamate, GABA, serotonin, adenosine and nitric oxide.

Question 33

How does synaptic transmission happen?

Answer 33

1) Acetyl choline is made from choline and acetyl CoA with choline acetyltransferase and stored at synaptic vesicles; action potential depolarises axon terminal. 2) Voltage gated Ca+ channels open, leading to Ca+ influx 3) Ca+ activates synapsin (protein which holds vesicles together) separation from synaptic vesicles 4) Free vesicle performs exocytosis with classical tethering mechanism with SNARE proteins 5) Acetyl choline diffuses through synaptic cleft and binds to the chemically gated channel or G-coupled protein 6) Acetyl choline quicky detaches from the receptor and degraded with acetylholinesterase back to choline and acetate 7) Choline gets back into pre-synaptic neuron with Na+ cotransport and is recycled.

Question 34

Are receptors the same for each neurotransmitter?

Answer 34

No, each neurotransmitter can bind to different receptor subtypes causing different effects.

Question 35

What is the difference between agonist and antagonist?

Answer 35

Both are competing to a certain substance. Agonist: still activates receptor after binding to it. Antagonist: blocks the receptor after binding to it. Nicotine is agonist for nicotinic cholinergic receptors, muscarine is agonist for muscarinic cholinergic receptors.

Question 36

The strength of action potential determines the strength of signal. True or false?

Answer 36

False. The strength of signal is determined by the frequency of the action potential. All of them have the same amplitude (the same strength). The bigger frequency, the more neurotransmitter is released.

Question 37

What is synaptic plasticity?

Answer 37

The change of activity on synapses. Convergent pathway - one post-synaptic neuron receives many pre-synapthic signals. Divergent pathway - one presynaptic neuron delivers many post-synaptic signals.

Question 38

What are the differences between spatial and temporal summation?

Answer 38

Spatial: additive effect of graded potentials from different synapses firing at the same time. Temporal: additive effect of graded potentials from the same synapse firing at very close time intervals.

Question 39

What are the features of somatic neuron pathways?

Answer 39

- The single neuron comes a spinal cord to the target muscle, there is no interruption of the signal. - Neurotransmitter: Acetyl choline acting on nicotinic cholinergic receptors.

Question 40

Where are the centres of autonomic nervous system?

Answer 40

Spinal cord and brain stem (vital reflexes such as breathing, salivation etc).

Question 41

What is the key parasympathetic nerve?

Answer 41

Vagus nerve, contains 75% of parasympathetic neurons. It is also the longest in the body. Controls breathing, heartbeat and digestion (blood pressure, temperature and water balance are regulated by other autonomic neurones). Belongs to cranial nerves.

Question 42

What is the difference between sympathetic and parasympathetic pathways at cellular and molecular level?

Answer 42

Sympathetic (normal): - short neuron before ganglion, acetyl choline with nicotinic receptor - long neuron after ganglion, noradrenaline with alpha and beta-1 receptors Adrenal sympathetic: - single neuron from a CNS triggers adrenal medulla with acetylcholine - adrenal medulla releases adrenaline into bloodstream - adrenaline reaches beta-2 receptors Parasympathetic: - long neuron before ganglion, acetyl choline with nicotinic receptor - short neuron after ganglion, acetyl choline with muscarinic receptor All of them target smooth and cardiac muscle, some glands and some fat.

Question 43

What are the integrating centres of the autonomic nervous system?

Answer 43

Hypothalamus, medulla (lower region in the brain stem), pons (higher region in the brain stem), some ganglia. Cerebral cortex and limbic system produce emotions which also cause autonomic responses like blushing, fainting etc.

Question 44

What is autonomic balance?

Answer 44

Sympathetic and parasympathetic system working in balance.

Question 45

What is Guillain-Barré syndrome?

Answer 45

A rare type of paralysis (progressive motor weakness) caused by neurone demyelination triggered by bacterial or viral infection, causing autoimmune attacks later. An Asian type of GBS, AMAN, is caused by damage (analogically triggered) of synapses on neuromuscular junctions.