Bioimaging and Brain Research

CORE I - WHY THE BRAIN IS THE BODY’S MOST COMPLEX ORGAN

Organization of Human Nervous System



The nervous system coordinates all the activities of the body’s cells, it controls all the activities

by the rapid communication between neurons (specialized nerve cells). The NS can be divided

in: Central Nervous System (CNS)



Includes all the nervous tissue contained within the brain and the spinal cord.

Integration:

- nerve cells receive the sensory input, analyse it, and make decision about

the appropriate response to make.

Peripherical Nervous System (PNS)



Includes all the nerves that enter or exit from the brain and spinal cord.

Sensory input or afferent neurons : nerve cells collect information about the external

o environment as well as the internal conditions of the body

Special sensory – send information about vision, hearing equilibrium, smell and taste

Somatic sensory – sends information about touch, temperature and tissue damage from

receptors in the skin, muscles and joints

Visceral sensory – carry information about conditions of various internal (visceral)

organs

Motor output or efferent neurons : nerve cells carry out the instructions that result

o from impulses sent to various effector organs that include muscles.

Somatic (voluntary) motor – control skeletal muscles

Autonomic (involuntary) motor – regulate cardiac and smooth muscle and glands

What is the nervous system made of?



Brain is composed by two kind of cells: Neuroglia or glial cells that are the 90% of the whole

brain, and Neurons, that are the other 10%. The adult human brain weighs about 1.3 Kg in

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women (it is about 1130 cm ) and 1.4 Kg in males (it is about 1260 cm ) because of they have

more glial cells. The number of neurons, according to array tomography, has been shown to be

on the average about 86billion in adult male human brain; 16 billion of them (19%) are in the

cerebral cortex (including subcortical white matter), 69 billion (80%) are in the cerebellum, and

1% are in the rest of the brain

Neuroglia or glial cells (90% of the brain cells):

 These cells form myelin, a fatty white substance that surrounds the

axon of the neuron, it’s essential for the proper functioning of the

nervous system. They provide nutrient for neurons, including

oxygen, destroy pathogens and provide a general support structure

in which neurons can sit.

There are 6 large type of glial cells:

Astrocytes: “star” ”cell”, a star-shaped cell, with tiny little feet they help to

o encircle the vessels that make up the blood- brain barrier, which is a barrier that helps

to prevent undesirable substances from entering the brain via blood vessels. In addition,

astrocytes are responsible for, provide nutrients for neurons, structural support of nerve

cells, repair of the nervous system, and help oligodendrocytes perform their job as well

Oligodendrocytes creates myelin sheaths around the axon of neurons in order to solve

o . (DIFFERENZA CON

their main function, provide support and insulation to axons

SHWANN)

Microglia are phagocytes that engulf pathogens such as bacteria

o Ependymal line the cavities of the brain and spinal cord. These cells regulate

o exchange between the cerebrospinal fluid (CSF) that is produced at specific locations

within the cavities of the brain and the nervous tissue if the CNS

Schwann surround and support the axons of the neurons of the PNS: these

o cells are also responsible for the formation of the myelin sheath. The myelin sheath

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results from supportive cells (Schwann cells or oligodendrocytes) wrapping around the

axon of a neuron in a jelly-roll fashion so that the axon comes to be surrounded by many

layers of plasma membrane. They also speed up the nerve impulse along the axon.

Ricorda gli oligodendrociti si trovano nel Sistema Nervoso Centrale, mentre le cellule di

Schwann in quello periferico.

Satellite are like Schwann cells except that they are fund around the cell’s

o bodies of

neurons in the

PNS Neurons (10% of brain cells):



In the NS there are more than 86 billion neurons that receive and

transmit information. There is a cell body, or soma, which

contains the nucleus of the cell and keeps the cell alive, a

branching treelike fibre known as the dendrite, which collects

information from others cells and sends the information to the

soma and a long, segmented fiber known as the axon, which

transmits information away from the cell body toward others

neurons or to the muscles and glands. There’s a wide variety in their shape size and

electrochemical proprieties in relation to the function performed in different parts of the

nervous system. There’s a different classification:

Structural classification linked to the number of process (dendrites or axon)

o extending from the soma

Unipolar neuron: has a single process extending from the cell body, this process

divides into two branches a short way from the cell body, one branch extends to the

CNS, the other to the periphery and has dendrite-like sensory receptor. This branch

could be considered a dendrite because it conducts action potentials toward the

neuron cell body.

Bipolar neuron: have two processes, one dendrite and one axon, the first is specialized

to receive a specific stimulus, the second conducts action potentials to the CNS, they are

found in eyes, nose ears.

Multipolar neuron: has many dendrites and one axon, 99% of the neurons in

the CNS are

multipolar, most of them are motor neurons

Functional classification

o

Sensory: carry impulses to the brain, detect changes inside and outside the body, begin in any

organ and end in CNS, most are unipolar, but some might be bipolar and at the end dendrites

are specialized to pick up signals from their environment

Motor: multipolar neurons that, employing peripherical neurons, carry messages from CNS to

effectors like glands and muscles 2

Interneurons: process, store and receive impulses from sensory receptors and made decision in

response. Made by multipolar, found in CNS, forms links between other neurons transmitting

signals from one part of CNS to another

Directional classification

o

Afferent (to the brain): all sensory neurons that carry the nerve impulse from the peripherical

body to the brain or spinal cord

Efferent (from the brain): all motor neuron that carry nerve impulse from the brain to the body

Spindle cells, interneurons that connect widely separated areas of the brain

NEURONAL COMUNICATION

 Resting Membrane Potential (stato con minore energia)

- when solutes such as

ions are placed in a solution without physical barrier, they become evenly distributed

throughout the solution by diffusion in order to reach the equilibrium. Neurons, like all

living cells, are surrounding by a plasma membrane that is impermeable to ions. This

property allows a neuron to maintain different concentrations of ions between the inside

and the outside of the cell by preventing the diffusion phenomena.

The only way that ions can diffuse across the membrane is by

passing through specialized channels that permit the

movement of particular ions while excluding others. These

channels can be in an open or closed state. The diffusion and

electrical forces eventually come into a balance, and an

electrical potential is achieved at which the electrical gradient

is exactly balanced by the diffusion gradient. This potential is

the equilibrium potential for K+ (potassium). At this

electrochemical equilibrium there is no net movement of K+ ion; on average, for each

K+ ion that leaves the cell, another returns, at this state the recorded value of the

membrane potential is about -60mV. This value represents the resting membrane

potential of the neuron. (valore della differenza di potenziale all’equilibrio

-60mV)

Action potential

- Neurons generate electrical signals that travel along their axons.

When a pulse of electricity reaches a junction called a synapse, it causes a chemical

neurotransmitter to be released, which binds to receptors on other cell and thereby

alters their electrical activity. In order to study how action

potentials are generated, we will insert two electrodes into the

neuron: one records the membrane voltage, the second injects

current that can be used to push the membrane voltage toward

more positive (depolarizing) or more negative (hyperpolarizing)

voltages. If the stimulus is insufficient to depolarize the membrane

no action potential is generated, and voltage returns to the resting

level. Instead, if a stimulus is large enough to push the membrane

potential to pass the firing threshold for the neuron (-40mV), it

generates an action potential. The higher pick of the action

potential is on 50 mV. NB a hyperpolarization current drives the

membrane potential in a negative direction, with the voltage

response of the cell is directly proportional to the magnitude of the injected current; the

same relationship is true for small injection of depolarizing current. To be noted that the

action potential is an all or none event (DOMANDA ESAME): once generated its

amplitude does not vary as a function of the size of the preceding stimulus – any

suprathreshold stimulus will produce an action potential pf similar amplitude and

duration. SI GENERA SOLO DOPO AVER TOCCATO I -40mV

The action potential could be divided in six phases:

(DOMANDA ) 1. Resting only the K+ channels are open (-60

mV 1-2 millliseconds)

2. Rising opening progressively more and more

voltage-gated Na+ channels. (-40 mV genera il

potenziale d’azione)

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3. Overshoot membrane potential has overshoot 0 mV. All this positive

potential, two processing are occurring simultaneously. First the voltage-gate

sodium channels that initially activated during the rising phase being to close. As

a result, sodium conductance starts to decline. Next potassium channel begins to

open, driving the membrane potential back toward the equilibrium potential for

K+

4. Falling the membrane potential is rapidly returning to the resting potential

5. Undershoot accurse because most voltage-gated potassium channels are

still open

6. Recovery occurs as the delayed potassium channels that were opened during

the action potential now close

- Impulse conduction in Axons The action potential is initiated at the beginning of the

axon, at what is called the initial segment. There is a high density of voltage-gated

+

Na channels so that rapid depolarization can take place here. Going down the length of

+

the axon, the action potential is propagated because more voltage-gated Na channels

+

are opened as the depolarization spreads. This spreading occurs because Na enters

through the channel and moves along the inside of the cell membrane. As the

+

Na moves, or flows, a short distance along the cell membrane, its positive charge

depolarizes a little more of the cell membrane. As that depolarization spreads, new

+

voltage-gated Na channels open and more ions rush into the cell, spreading the

+

depolarization a little farther. Because voltage-gated Na channels are inactivated at the

peak of the depolarization, they cannot be opened again for a brief time. Because of

this, depolarization spreading back toward previously opened channels has no effect.

The action potential must propagate toward the axon terminals; as a result, the polarity

of the neuron is maintained, as mentioned above. Propagation, as described above,

applies to unmyelinated axons. When myelination is present, the action potential

propagates differently. Sodium ions that enter the cell at the initial segment start to

spread along the length of the axon segment, but there are no voltage-gated

+

Na channels until the first node of Ranvier. Because there is not constant opening of

these channels along the axon segment, the depolarization spreads at an optimal

speed. The distance between nodes is the optimal distance to keep the membrane still

+

depolarized above threshold at the next node. As Na spreads along the inside of the

membrane of the axon segment, the charge starts to dissipate. If the node were any

farther down the axon, that depolarization would have fallen off too much for voltage-

+

gated Na channels to be activated at the next node of Ranvier (domanda

d’esame). If the nodes were any closer together, the speed of propagation would be

slower. Propagation along an unmyelinated axon is referred to

continuous conduction saltatory

as ; along the length of a myelinated axon, it is

conduction . Continuous conduction is slow because there are always voltage-gated

+ +

Na channels opening, and more and more Na is rushing into the cell. Saltatory

conduction is faster because the action potential basically jumps from one node to the

+

next (saltare = “to leap”), and the new influx of Na renews the depolarized membrane.

Along with the myelination of the axon, the diameter of the axon can influence the

speed of conduction. Much as water runs faster in a wide river than in a narrow creek,

+

Na -based depolarization spreads faster down a wide axon than down a narrow one.

- Synapse

Electrical (has direct physical contact) is mediated by clusters of intercellular channels

called gap junctions that connects the interior of two adjacent cells, and thereby directly

enable the bidirectional passage of electrical currents carried by ions. They are bidirectional

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in nature: when a presynaptic action potential propagates to the postsynaptic cell, the

membrane resting potential propagates to the postsynaptic cell, the membrane resting

potential of the postsynaptic cell