Chapter 3 - Neurophysiology

Question 1

What are the two types of cells that make up the nervous system?

Answer 1

Neurons and glia. Neurons are specialised to carry out the functions of information processing and communication, whereas glia serve a variety of support functions for neurons. Glial cells make up 85% of all the cells found in the CNS.

Question 2

What types of glia are there?

Answer 2

Glia are categorised by size in MACROGLIA - astrocytes, ependymal cells, oligodendrocytes, Schwann cells - and MICROGLIA.

Question 3

ASTROCYTES

Answer 3

Astrocytes - macroglial cells - are the most common type of glia in the brain. They have 5 functions:
1 - They provide a STRUCTURAL MATRIX for the neurons;
2 - Through their close association with the blood supply, they (A) help TRANSFER NUTRIENTS to neurons and (B) REGULATE BLOOD FLOW based on synaptic activity;
3 - They contribute to the protective BLOOD-BRAIN BARRIER - which prevents toxins circulating in the bloodstream from entering the brain - by covering the outer surface of capillaries with their endfeet.
4 - They surround and isolate the area of the synapse. In this way they:
(A) keep the neurochemicals released from moving outside a restricted area;
(B) remove excess potassium released by neurons from the extracellular fluid;
(C) signal the neurons to build synapses by releasing growth factors - fundamental in neural development and in learning and memory;
(D) excite and suppress the activity of neighbouring neurons and other astrocytes;
(E) remove neurochemicals from the synaptic cleft after the transmission of a signal.
5 - When CNS neurons are damaged, astrocytes PRODUCE SCAR TISSUE that fills the area previously occupied by the now dead neurons, and release chemicals that inhibit neural regrowth.

Question 4

EPENDYMAL CELLS

Answer 4

Ependymal cells are macroglial cells that cover the inner surface of the ventricles of the brain and of the central canal of the spinal cord. They have 5 functions:
1 - They feature fine hair-like cilia that project into a ventricle or the central canal and MOVE CEREBROSPINAL FLUID with a whip-like motion;
2 - Their cilia also absorb some CSF, allowing the ependymal cells to MONITOR THE CEREBROSPINAL FLUID and to supply underlying brain cells with proteins from the CSF;
3 - In the lateral ventricles, they ACTIVATE NEURAL STEM CELLS laying below them, which migrate to the olfactory bulbs, where they differentiate into new neurons;
4 - They ACT AS A FIREWALL against viruses attacking the central nervous system;
5 - In specific sites of the ventricles, special ependymal cells filter fluid from the CHOROID PLEXUS - a rich network of capillaries - to form the CSF.

Question 5

OLIGODENDROCYTES

Answer 5

Oligodendrocytes provide the myelin covering that insulates some nerve fibers or axons in the CNS. A single oligodendrocyte has several branches that wrap themselves around the axons of adjacent neurons and can myelinate axons from an average of 15 different neurons, thus providing structural support. They communicate with nearby axons through EXOSOMES, tiny ventricles which support transport within neurons and protect neurons from damage. Oligodendrocytes - unlike Schwann cells - cannot guide the regrowth of damaged axons.

Question 6

SCHWANN CELLS

Answer 6

Schwann cells provide the myelin covering that insulates some nerve fibers or axons in the PNS. Since one Schwann cell provides a single myelin segment on a peripheral axon, it takes large numbers of Schwann cells to myelinate a peripheral nerve. They communicate with nearby axons through EXOSOMES, tiny ventricles with which they can guide the regrowth of damaged axons.

Question 7

MICROGLIA

Answer 7

Microglia are tiny cells that serve as the brain’s cleanup crew, digesting dead neurons and glial cells. They play a role in the removal of less active synapses, which is an important part of the wiring of the developing brain. Uncontrolled activation of microglia can damage the brain - they have been observed digesting healthy cells located next to damaged cells.

Question 8

THE STRUCTURE OF NEURONS

Answer 8

Neurons, like all animal cells, have membranes, nuclei and organelles - which are found in the main mass of the neuron, known as cell body or soma. Neurons differ from other cells in that they have branches extending from the cell body - axons and dendrites - to communicate with other cells.

Question 9

NEURAL MEMBRANES

Answer 9

Neural membranes separate the intracellular fluid (cytoplasm) from the extracellular fluid surrounding neurons. A neural membrane is made up of a double layer of PHOSPHOLIPIDS, fatty molecules that do not dissolve in water - in this way, it is able to restrain the water-based fluids on either side. Suspended within this phospholipid membrane are a number of important pro­tein structures - ION PUMPS and ION CHANNELS - that control its permeability. These structures provide pores through which specific ions - electrically charged particles - can move into or out of the neuron. They show ion selectivity - the ability to let a particular type of ion pass and no others.

Question 10

ION CHANNELS

Answer 10

Ion channels allow ions to move passively, without the expenditure of energy. They have the ability to open and close in response to stimuli in their imme­diate vicinity and can be divided in VOLTAGE-DEPENDENT CHANNELS and LIGAND-GATED CHANNELS.
Voltage-dependent channels open and close in response to the electrical status of adjacent areas of membrane.
Ligand-gated channels open when they come in contact with specific chemicals.

Question 11

ION PUMPS

Answer 11

Ion pumps require energy to activate. The two most important ion pumps in neurons are sodium-potassium pumps and calcium pumps .
SODIUM-POTASSIUM PUMPS send 3 sodium ions out of the cell while collecting 2 potassium ions from the extracellular environment. To be activated, these pumps require a molecule of ATP - as much as 20 to 40 percent of the energy required by the brain is used to run the sodium-potassium pumps.
CALCIUM PUMPS are responsible for the active transport of calcium out of the cell.

Question 12

NEURAL CYTOSKELETON

Answer 12

The neural cytoskeleton is a network of filaments that provides the internal structure of a neuron - it is made up of three types of fibers.
MICROTUBULES, formed in the shape of hollow tubes, are responsible for the movement of var­ious materials within the cell, including the vesicles that contain neurochemicals. TAU is a protein that connects adjacent microtubules and holds them in place. TAU dysfunction is a frequent cause of cell death: if TAU proteins disconnect from microtubules (1) they form NEUROFIBRILLARY TANGLES and (2) this results in collapse of microtubules.
Neurofilaments and microfilaments are the other two types of fibers that make up the cytoskeleton and provide structural support, especially to axons and dendrites.

Question 13

NUCLEUS

Answer 13

It contains the DNA that directs the cell’s functions and the NUCLEOLUS.

Question 14

NUCLEOLUS

Answer 14

A small organelle contained in the nucleus that produces RIBOSOMES.

Question 15

RIBOSOMES

Answer 15

Organelles that pro­duce proteins either on their own or in association with the ENDOPLASMIC RETICULUM. They are produced by the NUCLEOLUS.

Question 16

ENDOPLASMIC RETICULUM

Answer 16

A cellular organelle that can be divided into ROUGH and SMOOTH portions: The rough endoplasmic reticulum has many RIBOSOMES bound to its surface, whereas There are no ribosomes attached to the smooth endoplasmic reticulum. The ribosomes on the rough portions produce protein that are then moved by the smooth ones to a GOLGI APPARATUS.

Question 17

GOLGI APPARATUS

Answer 17

Organelle that inserts the completed proteins - produced by ribosomes on rough endoplasmic reticulum and sent by the smooth one - into VESICLES, or small packages made out of membrane material.

Question 18

MITOCHONDRIA

Answer 18

The powerhouse of the cell. Mitochondria construct and release molecules of adenosine triphosphate (ATP), the major energy source for the neuron.
They differ from other organelles in that they have their own DNA and reproduce independently from the cell in which they exist. Mitochondria are inherited from the mother in most animal species. Sperm carry mitochondria in their tails, which drop off when they attach to an egg during fertilisation. As a result, the only version of mitochondria remaining in the fertilised egg comes from the mother.
Because mitochondrial DNA is not “shuffled” like nuclear DNA in each generation, it is particularly useful in tracking the course of evolution.

Question 19

DENDRITES

Answer 19

Dendrites are branches of a neuron that serve as locations at which information from other neurons is received. At each synapse on a dendrite, LIGAND-GATED ion channels serving as receptor sites are embedded in the neural membrane. Some dendrites form knobs known as DENDRITIC SPINES, additional locations for synapses to occur.

Question 20

THE AXON

Answer 20

The axon of a neuron is responsible for carrying messages to other neurons. The cone-shaped segment of axon that lies at the junction of the axon and the cell body is known as the AXON HILLOCK. The portion of axon between the hillock and the first segment of myelin is the INITIAL SEGMENT, where action potentials arise.
Towards their end, axons divide first in COLLATERALS and then in AXON TERMINALS, which contain both mitochondria and vesicles.
Axons vary in:
1 - Diameter, which is positively correlated with speed of signalling. In invertebrates, axons are significantly larger than in vertebrates;
2 - Length, which differentiates LOCAL CIRCUITS neurons from PROJECTION NEURONS;
3 - Myelination.

Question 21

DIFFERENCES BETWEEN MYELINATED AND UNMYELINATED AXONS

Answer 21

Axons vary in myelination: CNS neurons and peripheral motor neurons are myelinated, whereas peripheral sensory nerves may or may not be myelinated. Myelin does not cover the entire length of an axon - the axon hillock, the initial segment and the NODES OF RANVIER are completely uncovered, thus rich of ion channels.
Advantages of myelination:
1 - Myelin allows human axons to be smaller in diameter without sac­rificing transmission speed - the smaller the diameter of axons, the more neural tissue can be packed into skulls, the more information can be processed.
2 - Myelin reduces the energy requirements - there is no need for ion channels under a myelin sheath for little to no extracellular fluid is present there.

Question 22

STRUCTURAL VARIATIONS IN NEURONS

Answer 22

Neurons can be divided according to structural differences in UNIPOLAR, BIPOLAR and MULTIPOLAR neurons

Question 23

UNIPOLAR NEURONS

Answer 23

Unipolar neurons have a single branch extending from the cell body. They are typical of invertebrate nervous systems, whereas in vertebrates they can be found in the sensory systems.

Question 24

BIPOLAR NEURONS

Answer 24

Bipolar neurons have two branches extending from the neural cell body - one axon and one dendrite. VEN CELLS ( von Economo neurons, or SPINDLES), special bipolar neurons found in the ANTERIOR CINGULATE CORTEX, appear to be specifically designed to provide fast, intuitive assessments of complex situations.

Question 25

MULTIPOLAR NEURONS

Answer 25

Multipolar neurons, the most common ones, have have many branches extending from the cell body, yet usually one axon and several dendrites. They can take different shapes:

• PYRAMIDAL CELLS, neurons with pyramid-shaped cell bodies, are found in the cortex and in the hippocampus;
• PURKINJE CELLS, neurons with dramatic dendritic trees that allow a single cell to form as many as 1 50,000 synapses, are found in the cerebellum.

Question 26

FUNCTIONAL VARIATIONS IN NEURONS

Answer 26

Neurons can be divided according to functional differences in:

• SENSORY NEURONS, which receive information from the outside world and from within our bodies;
• MOTOR NEURONS, which transmit signals from the CNS directly to muscles and glands;
• INTERNEURONS, unspecialised neurons that connect the sensory and motor systems.

Question 27

IONIC COMPOSITION OF INTRACELLULAR AND EXTRACELLULAR FLUIDS

Answer 27

The intracellular and extracellular fluids differ from each other in the relative concentrations of ions they contain.
Extracellular fluid is characterized by large concentrations of SODIUM and CHLORIDE ions and a relatively small concentra­tion of POTASSIUM ions - it is similar to sea water.
Intracellular fluid contains large numbers of POTASSIUM ions, relatively few SODIUM and CHLORIDE ions and large PROTEINS in ion form that are NEGATIVELY CHARGED.
Because of these differences, the electrical environment inside the neuron is more neg­ative than it is on the outside

Question 28

RESTING POTENTIAL

Answer 28

The resting potential is the difference of potential energy between the inside and outside of a neuron, which is approximately 70mV. It is the result of the different ionic compositions of intracellular and extracellular fluids. The resting potential in a neuron is dependent on the movement of potassium - ASTROCYTES have the important task of collecting excess potassium in the vicinity of neurons.

Question 29

MOVEMENTS OF IONS ACROSS THE MEMBRANE

Answer 29

Ions in both the extracellular and intracellular fluids are moved by two forces:
-DIFFUSION, the tendency for molecules to distribute themselves equally within a medium;
-ELECTROSTATIC PRESSURE, the psychical law by which oppositely charged ions attract and likely charged ions repel.
For all three types of ions present in the cellular fluid, these forces result in equilibrium:
- for POTASSIUM and CHLORIDE, the two forces are balanced because they have different directions;
- for SODIUM, both diffusion and electrostatic pressure work in the same direction. Still, most sodium is found outside of the cell because sodium channels are closed when the cell is at rest. Furthermore, whenever sodium leaks into the cell, sodium-potassium pumps are quick to restore balance.

Question 30

ACTION POTENTIALS

Answer 30

An ACTION POTENTIAL is an ALL-OR-NONE phenomenon.
When the cell is DEPOLARISED - the interior of the cell is more similar to the exterior - and the THRESHOLD (-65 to -60 mV) is reached, an action potential is produced. VOLTAGE-DEPENDENT SODIUM CHANNELS open as a result of depolarisation of the membrane and sodium ions quickly leak in, helped by both diffusion and electrostatic pressure. The inside of the neuron is now positively charged (+40 mV) relative to the extracellular fluid. VOLTAGE-DEPENDENT POTASSIUM CHANNELS are also triggered at threshold, but their response is much slower than the sodium channels. Toward the peak of the action potential, potassium - attracted by the now relatively negative extracellular environment - begins to leave the cell, and the recording not only drops back to rest­ing levels, but it actually HYPERPOLARISES (the inside of the cell is even more negative than when at rest). This happens because not only are potassium channels much slower than sodium channels, but the former remain open for much longer than the latter. Thus, as the sodium ions are prevented from entering the cell because their channels are locked, as the SODIUM-POTASSIUM PUMPS are hard at work to return sodium ions to the extracellular fluid, potassium is still free to leave the cell and hyperpolarize it. As potassium channels close, the cell slowly return to its resting levels.

Question 31

REFRACTORY PERIODS

Answer 31

The frequency with which neurons can fire is limited.
The ABSOLUTE REFRACTORY PERIOD is the interval in which no stimulus whatsoever can produce another action potential because VOLTAGE-DEPENDENT SODIUM CHANNELS cannot be activated until the membrane is depolarised to nearly resting levels.
The RELATIVE REFRACTORY PERIOD is the interval following an action potential in which an action potential can be produced, but only by larger than normal input because the cell is still HYPERPOLARISED.

Question 32

PROPAGATION of ACTION POTENTIALS

Answer 32

PROPAGATION is the process by which an action potential formed at the initial segment is then reproduced down the length of an axon. Once SODIUM IONS enter the cell, some of them will exit the cell through sodium-potassium pumps, and others will drift to the adjacent axon segment - where there are many additional sodium channels - because of diffusion and electrostatic pressure. At the same time, incoming positive sodium ions will also push positive POTASSIUM IONS ahead into adjacent axon segments due to their like electrical charges - both depolarising the cell. If the threshold is reached once again, the action potential will be reproduced.
Action potentials are unidirectional - the prior segment (in which the action potential has already been transmitted) will still be in REFRACTORY PERIOD and won’t be able to fire.

Question 33

SALTATORY CONDUCTION

Answer 33

Propagation in the myelinated axon is referred to as SALTATORY CONDUCTION. In myelinated axons, the myelin sheath prevents leakage of the sodium ions, at least until they reach a NODE of RANVIER. Here -where the density of channels is about 10 times greater than the density of channels on an unmyelinated axon - another action potential is reproduced.

Question 34

SYNAPSES

Answer 34

SYNAPSES - structures that permit a neuron to pass on a signal - can be divided in GAP JUNCTIONS (or electrical synapses) and CHEMICAL SYNAPSES

Question 35

GAP JUNCTIONS

Answer 35

In GAP JUNCTIONS, channels connecting the two neurons across a tiny synaptic gap allow for the direct movement of ions from one cell to the other. They have the advantage of nearly INSTANTANEOUS COMMUNICATION between neurons (they are often found in circuits responsible fro escape behaviour) but the only type of message they can transmit is an EXCITATORY one.

Question 36

CHEMICAL SYNAPSES

Answer 36

At CHEMICAL SYNAPSES neurons stimulate other cells by releasing neurochemicals. Signaling at chemical synapses occurs in three steps:

• release of neurochemicals by a presynaptic cell;
• reaction of postsynaptic cell to neurochemicals;
• termination of the chemical signal.

Question 37

WIRING TRANSIMSSION vs VOLUME TRANSIMISSION

Answer 37

There are two types of intercellular chemical communication in the central nervous system:
-in WIRING TRANSMISSION, chemicals and ions diffuse from one cell to impact an adjacent cell or cells through private, highly localized channels.
- in VOLUME TRANSMISSION, neurochemicals diffuse through the extracellular fluid and CSF to influence cells located some distance away from the releasing cell.
Chemical synapses can take these two forms, whereas gap junctions engage in wiring transmission only.

Question 38

NEUROCHEMICAL RELEASE at a SYNAPSE

Answer 38

As an action potential arrives at a terminal, VOLTAGE-DEPENDENT CALCIUM CHANNELS open and positively charge calcium ions - more abundant in the extracellular fluid - enter the presynaptic cell. Calcium channels are rare along the length of the axon, but there are a large number located in the axon terminal membrane. Once calcium ions enter, it triggers the release of neurochemicals by freeing the VESICLES from their protein anchors. Once again, calcium promotes the fusion between the membrane of the vesicle and the membrane of the axon terminal, a process known as EXOCYTOSIS.
Following the release of neurochemicals into the synaptic cleft, CALCIUM PUMPS return calcium ions to the extracellular fluid. Furthermore, vesicle waste produced by exocytosis is recycled to prevent gradual thickening of the presynaptic membrane.

Question 39

REACTION of POSTSYNAPTIC CELL to NEUROCHEMICALS

Answer 39

On the postsynaptic side of the synapse, proteins embedded in the postsynaptic cell membrane - RECEPTORS - interact with the neurochemicals released by the presynaptic cell. Receptors can be either ionotropic or metabotropic.

• in IONOTROPIC RECEPTORS, the recognition site is located directly on a ligand-gated ion channel, which changes its configuration and opens as soon as the receptor comes into contact with the neurochemical.
• in METABOTROPIC RECEPTORS, the recognition site does not have direct control on an ion channel, but releases G PROTEINS on the intracellular side when stimulated by neurochemicals. G protein separates from the receptor complex and moves to open ion channels in the nearby membrane. Metabotropic receptors respond more slowly, but the effects of their activation can lust much longer than those produced by ionotropic activation.

Question 40

TERMINATION of THE CHEMICAL SIGNAL

Answer 40

Neurochemicals bind very briefly to receptors, after which they are released back into the synaptic gap. Here, neurochemicals must be deactivated for a second message to be transmitted. This happens in 4 different ways:

1. Through DIFFUSION - neurochemicals diffuse away from areas of high concentration to areas of low concentration. This process is limited by the action of astrocytes, which oppose neurochemical diffusion away from the synapse;
2. Through ENZYMATIC DIGESTION in the synaptic gap;
3. Through REUPTAKE, the process by which TRANSPORTERS - presynaptic receptors - recapture molecules of neurochemical and return them to the interior of the axon terminal where they can be recycled.
4. Through pumps located on nearby ASTROCYTES which absorb neurochemical molecules.

Question 41

POSTSYNAPTIC POTENTIALS

Answer 41

When molecules of neurochemical bind to postsy­naptic receptors, they can produce one of two outcomes:
1. EXCITATORY POSTSYNAPTIC POTENTIALS (EPSP), which increase the likelihood that the postsynaptic cell will generate an action potential. They result from the opening of ligand-gated SODIUM CHANNELS which depolarises the membrane.
2. INHIBITORY POSTSYNAPTIC POTENTIALS (IPSP), which decrease the likelihood that the postsynaptic cell will generate an action potential. They result from the opening of ligand-gated channels that allow for the inward movement of CHLORIDE (CI-) or the outward movement of POTASSIUM (K+), which polarise the cell.
Unlike action potentials, both EPSP and IPSP are GRADED POTENTIALS, meaning they vary in size and shape.

Question 42

NEURAL INTEGRATION

Answer 42

Neurons receive input from thousands of other neurons - some of that input will be in the form of EPSPs, and some in the form of IPSPs.
NEURAL INTEGRATION is the process by which neurons determine wether to produce an action potential or not. The cell will produce an action potential only when the area of the axon hillock is depolarised to threshold, which occur as the result of:
- SPATIAL SUMMATION, in which the cell adds up all the excitatory inputs and subtracts all the inhibitory inputs converging to the hillock;
- TEMPORAL SUMMATION, in which EPSPs and IPSPs from a single, very active synapse build on one another.

Question 43

AXO-AXONIC SYNAPSES

Answer 43

AXO-AXONIC SYNAPSES are synapses between an axon terminal and another axon fiber which have a modulating effect on the release of neurochemical by the target axon. PRESYNAPTIC FACILITATION increases such release, whereas PRESYNAPTIC INHIBITION reduces it.