neurophysiology,dr sravanti
TRANSCRIPT
Neurophysiology
-Dr Sravanthi
OBJECTIVES
INTRODUCTION
NEURON AND TYPES
RESTING POTENTIAL
ACTION POTENTIAL
SYNAPSE AND TYPES
REFLEX ARC
NEUROTRANSMITTERS AND TYPES
NERVOUS SYSTEM
The Neuron
The nervous system is made of nerve
cells or neurons and glial cells. Glial
cells are not excitable and provide
metabolic and physical support for the
neurons. 90% of the cells are glial cells.
Neurons are excitable and control
behavior
STRUCTURE
TYPES
Ion channels
Resting potential
There is a potential
difference between the
inside and outside of
as membrane. The
inside is about -70 mv
relative to the outside.
Resting Potential
The resting potential is
caused by an uneven
distribution of ions
(electrically charged
molecules) of potassium
(K+) and sodium (Na+)
and chloride (Cl-).
This is caused by Na+/K+
ion pumps that move 3
Na+ ions out of the cell for
every 2 K+ ions it moves
in.
Therefore there are more
+ions outside the cell than
inside and the inside is
negatively charged with
respect to the outside
Ion pump
Resting potential
Forces maintaining the resting potential
Diffusion pressure – molecules want to move
from areas of high concentration to areas of
low concentration.
Electrostatic charge – ions with like charge
are repelled and ions with a different charge
are attracted.
Operation of ion pumps and ion channels.
Action potential
Anything that alters the functioning of the ion
channels can change the resting potential.
If changes cause the resting potential to be
reduced, this is called depolarization.
If the change causes an increase in the resting
potential, this is caused hyperpolarization.
Action potential
ACTION POTENTIAL 1.AP, activation of the voltage-dependent
Na+ channels (soma, area of the initial
segment)
2. ADP, after-depolarization, acctivation of
a high threshold Ca2+ channels, localized
in the dendrites
3.AHP, after-hyperpolarization, Ca2+
sensitive K+ channels
4.Rebound depolarization, low threshold
Ca2+ channels, de-inactivated during the
AHP, activated when the depolarization
decreases (probably localized at the level
of the soma
Action potential
Voltage gated ion channels open and let Na+ into the cell. They are driven into the cell because of diffusion gradient and electrostatic charge.
This causes the resting potential to reverse, i.e., the inside the cell becomes positive.
Now the Na+ ion channels close and the K+ channels open and the K+ ions are driven out of the cell because of their concentration gradient and electrostatic charge.
Finally the K+ channels close and the ion pumps kick in and the resting potential returns to normal.
All or None Law
Action potentials when they occur are
always the same.
Once the process is initiated, it must run
its course and nothing can stop it or
change it
Transmission of action potentials
along a membrane
When an action potential occurs at one
place on the membrane of an axon, the
surrounding membrane is depolarized past
threshold causing an action potential. This
depolarizes the neighboring membrane,
etc.
Action potentials sweep across a
membrane as fast as 100m/sec
Transmission of action potentials
along a membrane
SYNAPSE
A junction that mediates information
transfer from one neuron:
To another neuron
To an effector cell
Presynaptic neuron – conducts impulses
toward the synapse
Postsynaptic neuron – transmits impulses
away from the synapse
Junction between two cells
Site where action potentials in one cell
cause action potentials in another cell
Types of cells in synapse
Presynaptic
Postsynaptic
TYPES a)axosomatic
b)axodendritic
c)axoaxonic
TYPES: A)CHEMICAL
SYNAPSE Components
Presynaptic terminal
Synaptic cleft
Postsynaptic membrane
When an action potential arrives at the terminal
bouton, it causes Ca++ channels to open.
This causes the vesicles to move to the membrane and release a chemical called a neurotransmitter to be released into the synaptic cleft.
The neurotransmitter diffuses across the cleft and activates receptors on the postsynaptic membrane which cause changes on the resting potential by altering the functioning of ion channels.
B)ELECTRICAL SYNAPSE
Synapse
Any neuron can have thousands of synapses on it
Postsynaptic potentials
The membranes of dendrites and cell
bodies do not have action potentials.
Instead, any depolarizing stimulus causes
a post synaptic potential (PSP) which
spreads out across the membrane. The
depolarization is weaker the further it gets
from the stimulus. When the stimulus is
turned off, the PSP disappears.
Postsynaptic potentials
Postsynaptic potentials can either be excitatory (depolarization) or inhibitory.
Excitatory and inhibitory potentials can summate both in time (temporal summation) and across the membrane (spatial summation) .
The net effect of summation is reflected at the axon hillock where action potentials are generated.
Post synaptic potential
The change in the resting potential caused by the activation of a receptor site is called the post synaptic potential (PSP).
IPSP – when the change causes hyperpolarization or makes the cell harder to fire, this is called an inhibitory post synaptic potential.
EPSP – when the change causes depolarization, this is called an excitatory post synaptic potential.
RESTING,EXCITED,INHIBITED
NEURON
Post synaptic potential
The excitation and inhibition caused by all
the active synapses on the dendrites and
cell body are summed and the net effect
is reflected in the rate at which the axon
hillock generates action potentials
Summation
SUMMATION
Dale’s Law
A single neuron always produces the same
transmitter at every one of its synapses.
It is now known that the law is not always right.
Terminating synaptic action
Once the neurotransmitter is released into
the cleft, there must be a means by which
its activity is terminated. This can be
accomplished two ways
The neurotransmitter can be destroyed by an
enzyme in the cleft
The neurotransmitter can be reabsorbed back
into the bouton (reuptake).
NEUROTRANSMITTER
REMOVAL
Proteins
Ion pumps, ion channels, etc., are large
molecules of protein.
Proteins are long strings of amino acids that can
fold into many three dimensional shapes. The
same protein can have different configurations,
i.e., they can change shape.
Receptors are protein molecules that change
shape (are activated) by neurotransmitter
molecules with a particular shape.
Receptors
Receptor sites can be
part of an ion channel
and when the
receptor site is
occupied by a
neurotransmitter, the
ion channel opens
Reflex arc
Knee-jerk reflex
COMPONENTS
Research on reflexes
Sir Charles Scott Sherrington
Great Britain
nobelist 1932
Ivan Petrovich Pavlov
Russia
nobelist 1904
Behavior as a chain of reflexes?
LOCUST
Two pairs of wings
Each pair beat in
synchrony but the rear
wings lead the front wings
in the beat cycle by about
10%
Proper delay between
contractions of the front
and rear wing muscles
Second messenger cascade
Second messenger molecules can activate a kinase which lasts for minutes and hours.
Kinases can activate transcription factors (CREB and c-fos) which alter the expression of genes.
Genes carry the codes for the creation of proteins including ion channels and receptor sites and this can cause permanent changes in synaptic function.
autoreceptors
The membrane of the presynaptic cell has
many receptor sites which detect the
neurotransmitter. This is a feedback
system which regulated the amount of
neurotransmitter released into the cleft
Other signaling between neurons
Neuromodulators are chemicals that can alter the effect of a neurotransmitter.
Sometimes the postsynaptic membrane releases molecules that affect the presynaptic membrane.
DSE- depolarization-induced suppression of excitation
DSI – depolarization-induced suppression of inhibition.
Axo-axonal synapses: axons may also have synapses
NEUROTRANSMITTERS
Chemicals used for neuronal communication
with the body and the brain
50 different neurotransmitters have been
identified
Classified chemically and functionally
Chemically:
• ACh, Biogenic amines, Peptides
Functionally:
• Excitatory or inhibitory
• Direct/Ionotropic (open ion channels) or
Indirect/metabotropic (activate G-proteins) that
create a metabolic change in cell
types
EXCITATORY
Acetylcholine
Aspartate
Dopamine
Histamine
Norepinephrine
Epinephrine
Glutamate
Serotonin
INHIBITORY
GABA
Glycine
CHEMICAL-NT’S
Acetylcholine (ACh)
Biogenic amines
Amino acids
Peptides
Novel messengers: ATP and dissolved
gases NO and CO
BIOGENIC-NT’S
Include:
Catecholamines – dopamine, norepinephrine
(NE), and epinephrine (EP)
Indolamines – serotonin and histamine
Broadly distributed in the brain
Play roles in emotional behaviors and our
biological clock
AMINO ACID-NT’S
Include:
GABA – Gamma ()-aminobutyric acid
Glycine
Aspartate
Glutamate
Found only in the CNS
PEPTIDES-NT’S
Include: Substance P – mediator of pain signals
Beta endorphin, dynorphin, and enkephalins
Act as natural opiates, reducing our perception of pain Found in higher concentrations in marathoners and
women who have just delivered
Bind to the same receptors as opiates and morphine
Neurohormones
Substances that act at neuron receptor
sites, but are not specific to an individual
synapse.
May be released far from the synapse.
Act as a neuromodulator (modify the
activity of a neurotransmitter)
NOVEL MESSENGERS-NT’S
Nitric oxide (NO)
A short-lived toxic gas; diffuses through post-synaptic
membrane to bind with intracellular receptor
(guanynyl cyclase)
Is involved in learning and memory
Some types of male impotence treated by stimulating
NO release (Viagra)
• Viagra NO release cGMP smooth muscle relaxation
increased blood flow erection
• Can’t be taken when other pills to dilate coronary b.v. taken
Carbon monoxide (CO) is a main regulator of
cGMP in the brain
Drugs mostly act on the nervous system by
interacting with neurotransmission,
They may:
act on receptor sites and cause the same effect as a
transmitter: agonism
block a receptor site: antagonism
decreasing activity of enzymes that destroy a
transmitter
block reuptake mechanisms
blocking ion channels
altering release of transmitter
altering the action of neurohormones
Synapses that use NE are nor adrenergic (remember,
adrenaline is another word for epinephrine)
DA are dopaminergic
5-HT are serotonergic
ACh are cholinergic
etc
Acetylcholine:
Broken down by AchE (acetylcholinesterase)
Receptors: nicotinic and muscarinic
Stimulated Blocked Function
nicotinic nicotine curare Voluntary muscle control
(neuromuscular junctions)
muscarinic muscarine atropine Involuntary muscle control
botox and nerve gasses
Biogenic amines
Serotonin, Dopamine Norepinephrine and
Epinephrine
Broken down by MAO and COMT
Reabsorbed by transporter mechanisms
Influenced by amphetamines and cocaine and SSRIs and
SNRIs
E and NE receptor sites alpha (α)and Beta (β) with
subtypes 1 and 2
DA has 6 receptor subtypes D1 and D2....D6 with sub sub
types a b c, etc
Serotonin has 4 main receptor subtypes with sub sub
types a b c etc.
GABA
Universally inhibitory transmitter
Opens a Chloride ion channel which stabilizes the
membrane and makes it harder to depolarize
Drugs like benzodiazepines enhance the ability of GABA
to open the ion channel.
There are two types of GABA receptors; GABAA and
GABAB.
There are many different subtypes of GABAA receptors
which control different functions.
GABAB receptors are less common and use a second
messenger
GABA
Glutamate
excitatory transmitter
NMDA receptor open ion channel and lets +ions
into the cell
the channels can be blocked by alcohol, solvents
and some hallucinogens
Peptides
opioid type peptides
enkephalins (5 amino acids)
endorphines (16 to 30 amino acids)
Receptor subtypes mu, kappa and delta
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