neural control mechanism -2 Flashcards
1
Q
neurons
A
The basic unit of the nervous system is the individual
nerve cell, or neuron .
Neurons operate by generating electrical signals that
move from one part of the cell to another part of the same
cell or to neighboring cells.
2
Q
nervous system is divided into
A
(1) the central nervous system (CNS) , composed of the
brain and spinal cord; and
(2) the peripheral nervous system (PNS) ,consisting of the
nerves that connect the brain and spinal cord with the body’s
muscles, glands, sense organs, and other tissues
3
Q
neurtransmitters
A
The electrical signal causes the release of chemical
messengers—neurotransmitters —to communicate with
other cells.
4
Q
cell body
A
- Cell body (Soma): contains the nucleus and ribosomes and
thus has the genetic information and machinery necessary for
protein synthesis.
5
Q
dendrites
A
- Dendrites: series of highly branched outgrowths of the cell
body
Branching dendrites increase a cell’s surface area—some
neurons may have as many as 400,000 dendrites
Knoblike outgrowths called dendritic spines increase the
surface area
The presence of protein synthesis machinery allows dendritic
spines to remodel their shape in response to variation in
synaptic activity (like learning and memory)
6
Q
axon
A
- Axon(nerve fiber): a long process that extends from the cell body and carries outgoing signals
to its target cells
Range in length from a few microns to over a meter
Region of the axon that arises from the cell body (initial segment or axon hillock ) also
termed as “trigger zone”
The axon may have branches, called collaterals . The greater the degree of branching of the
axon and axon collaterals, the greater the cell’s sphere of influence
Each branch ends in an axon terminal , which is responsible for releasing neurotransmitters
from the axon
Alternatively, some neurons release their chemical messengers from a series of bulging areas
along the axon known as varicosities .
The axons of many neurons are covered by sheaths of myelin, usually consists of 20 to 200
layers of highly modified plasma membrane
In the brain and spinal cord, these myelin-forming cells are the oligodendrocytes . Each
oligodendrocyte may branch to form myelin on as many as 40 axons
7
Q
schwann cells
A
In the PNS, cells called Schwann cells form individual myelin sheaths surrounding 1- to
1.5-mm-long segments at regular intervals along some axons
8
Q
node of ranvier
A
The spaces between adjacent sections of myelin where the axon’s plasma membrane is
exposed to extracellular fluid are called the nodes of Ranvier
9
Q
maintence of structure and function of cell axon
A
Various organelles and other materials must move as far as 1 meter between the cell
body and the axon terminals. This movement, termed axonal transport , depends
on a scaffolding of microtubule “rails” running the length of the axon and
specialized types of motor proteins known as kinesins and dyneins ( Figure 6.3 ).
At one end, these double-headed motor proteins bind to their cellular cargo, and the
other end uses energy derived from the hydrolysis of ATP to “walk” along the
microtubules.
10
Q
kinesin
A
Kinesin transport mainly occurs from the cell body toward the axon terminals (
anterograde ) and is important in moving nutrient molecules, enzymes,
mitochondria, neurotransmitter-filled vesicles, and other organelles.
11
Q
dyein
A
Dynein
movement is in the other direction ( retrograde ), carrying recycled membrane
vesicles, growth factors, and other chemical signals that can affect the neuron’s
morphology, biochemistry, and connectivity. Retrograde transport is also the route
by which some harmful agents invade the CNS, including tetanus toxin and the
herpes simplex, rabies, and polio viruses.
12
Q
neurons can be divided into
A
affert neurns
effernt neurons
interneurons
13
Q
afferent neuron
A
Afferent nuerons: convey information from the tissues and organs
of the body toward the CNS
At their peripheral ends have sensory receptors , which respond to
various physical or chemical changes in their environment by
generating electrical signals in the neuron
Structurally different, two branched axon, one is peripheral process,
begins where the dendritic branches converge from the receptor
endings. The other branch, central process, enters the CNS to form
junctions with other neurons
Cell body and the long axon are outside the CNS
14
Q
efferent neurons
A
convey information away from the CNS to
effector cells like muscle, gland, or other cell types
Conventional neuronal structure (refer to figure) Their cell bodies and
dendrites are within the CNS
15
Q
interneuron
A
Interneurons: connect neurons within the CNS
Lie entirely within the CNS
They account for over 99% of all neurons and have a wide range
of physiological properties, shapes, and functions.
The number of interneurons interposed between specific afferent
and efferent neurons varies according to the complexity of the
action they control.
Example: The knee-jerk reflex elicited by tapping below the
kneecap activates thigh muscles without interneurons. In
contrast, to hear a song or smell a certain perfume that evokes
memories of someone you know, millions of interneurons may
be involved
16
Q
synapse
A
Synapse: The anatomically specialized junction between two
neurons where one neuron alters the electrical and chemical
activity of another.
Most synapses occur between an axon terminal of one neuron
and a dendrite or the cell body of a second neuron
A neuron that conducts a signal toward a synapse is called a
presynaptic neuron , whereas a neuron conducting signals
away from a synapse is a postsynaptic neuron
17
Q
glial cells
A
Neurons account for only about half of the cells in the
human CNS. The remainder are glial cells ( glia, “glue”).
Glial cells surround the soma, axon, and dendrites of
neurons and provide them with physical and metabolic
support
Glial cells retain the capacity to divide throughout life.
Consequently, many CNS tumors actually originate from
glial cells
18
Q
types of glial cells
A
oligodendrocyte
astrocyte
microglia
epndymal cells
schwann cells
19
Q
oligodendrocyte
A
which forms the myelin sheath of CNS axons
20
Q
astrocyte
A
helps regulate the composition of the
extracellular fluid in the CNS by removing potassium ions
and neurotransmitters around synapses
formation of tight junctions between the cells that make up the
walls of capillaries in CNS, which forms Blood brain barrier
Astrocytes also sustain the neurons metabolically—for example,
by providing glucose and removing ammonia.
In developing embryos, astrocytes guide neurons as they migrate
to their ultimate destination, and they stimulate neuronal growth
by secreting growth factors.
21
Q
microglia
A
The microglia: a third type of glial cell, are specialized,
macrophage-like cells (Chapter 18) that perform immune functions
in the CNS, and may also contribute to synapse remodeling and
plasticity.
22
Q
eondymal cells
A
ependymal cells line the fluid-filled cavities within the brain and
spinal cord and regulate the production and flow of cerebrospinal
fluid
23
Q
schwann cells
A
Schwann cells, the glial cells of the PNS, have most of the
properties of the CNS glia.
24
Q
neural growth and regenerations
A
Neuronal cells or glia develops from stem cells in embryo
Each neuronal daughter cell differentiates, migrates to its
final location, and sends out processes that will become its
axon and dendrites.
A specialized enlargement, the growth cone , forms the
tip of each extending axon and is involved in finding the
correct route and final target for the process
25
neurotrophic factors
Axon growth is guided by the glial cells through
attracting, supporting, deflecting, or inhibiting influences
exerted by several types of molecules (cell adhesion
molecules) or soluble neurotrophic factors (growth
factors for neural tissue)
26
neuronal current
The predominant solutes in the extracellular fluid are
sodium and chloride ions. The intracellular fluid contains
high concentrations of potassium ions and ionized
non-penetrating molecules, particularly phosphate
compounds and proteins with negatively charged side
chains.
Electrical phenomena resulting from the distribution of
these charged particles occur at the cell’s plasma
membrane and play a significant role in signal integration
and cell-to-cell communication, the two major functions
of the neuron.
27
basic elctrical facts
Same charges repel each other and opposite charges attract
each other if not separated by barriers
Separated electrical charges of opposite sign have the
Potential known as electrical potential
It is determined by the difference in the amount of charge
between two points, a potential difference
The units of electrical potential are volts or milli volts.
The movement of electrical charge is called a current
The hindrance to electrical charge movement is known as
resistance
The effect of voltage V and resistance R on current I is
expressed in Ohm’s law : (I=V/R)
Material with high electrical resistance (insulators) vs low
electrical resistance(Conductors)
Therefore, the lipids of membranes are insulators and ion
dissolved in water (ECF connected through channels) is
conductor
28
resting membrane potential
“All cells under resting conditions (when no current flows
through) have a potential difference across their plasma
membranes, with the inside of the cell negatively charged
with respect to the outside ( Figure 6.8 ), termed as
resting membrane potential”.
ECF is used as voltage reference point
The magnitude of the resting membrane potential varies
from about 5 to 100 mV, depending upon the type of cell.
In neurons its (40-90mV)
29
ion in membrane
Ions that can flow across the membrane and affect its
electrical potential, Na, K, and Cl are present in the
highest concentrations, and the membrane permeability to
each is independently determined.
Na and Cl concentrations are lower inside the cell than
outside, and that the K concentration is greater inside the
cell
This difference is established by (Na/K –ATPase) Na out
of the cell and K into it
30
magnitude of resting membrane potential depends upon
The magnitude of the resting membrane potential depends
mainly on two factors:
(1) differences in specific ion concentrations in the
intracellular and extracellular fluids; and
(2) differences in membrane permeabilities to the different
ions, which reflect the number of open channels for the
different ions in the plasma membrane.
31
equlibrium potential
The membrane potential at which these two fluxes become
equal in magnitude but opposite in direction is called the
equilibrium potential for that ion—in this case, K+.
32
permeabiity of membrane
Plasma membrane Na/K-ATPase pumps maintain low
intracellular Na concentration and high intracellular K
concentration.
In almost all resting cells, the plasma membrane is much
more permeable to K than to Na, so the membrane
potential is close to the K equilibrium potential—that is,
the inside is negative relative to the outside.
The Na /K -ATPase pumps directly contribute a small
component of the potential because they are electrogenic.
33
graded and action potentials
Some cells have another group of ion channels that can be gated
(opened or closed) under certain conditions. Such channels give a
cell the ability to produce electrical signals that can transmit
information between different regions of the membrane.
This property is known as excitability , and such membranes are
called excitable membranes .
Cells of this type include all neurons and muscle cells, as well as
some endocrine, immune, and reproductive cells.
The electrical signals occur in two forms: graded potentials and
action potentials.
Graded potentials are important in signaling over short distances.
Action potentials are long-distance signals that are particularly
important in neuronal and muscle cell membranes.
34
graded potential
“Graded potentials are local potentials whose magnitude can vary
and that die out within 1 or 2 mm of their site of origin”.
Changes in membrane potential that are confined to a relatively
small region of the plasma membrane.
Produced when some specific change in the cell’s environment acts
on a specialized region of the membrane.
They are called graded potentials simply because the magnitude of
the potential change can vary
Graded potentials are given various names related to the location of
the potential or the function they perform—for instance, receptor
potential, synaptic potential, and pacemaker potential are all
different types of graded potentials
35
action potential
“An AP is a rapid change in the membrane potential during
which the membrane rapidly depolarizes and repolarizes. At
the peak, the potential reverses and the membrane becomes
positive inside. APs provide long-distance transmission of
information through the nervous system”.
Generally very rapid (as brief as 1–4 milliseconds)
Propagates to long distances
Large alterations in the membrane potential; might be up to
100 mV. For example, a cell might depolarize from -70 to 30
mV, and then repolarize to its resting potential.
36
more about action potentials
APs occur in excitable membranes because these membranes contain many voltage-gated Na
channels.
These channels open as the membrane depolarizes, causing a positive feedback opening of
more voltage-gated Na channels and moving the membrane potential toward the Na
equilibrium potential.
The AP ends as the Na channels inactivate and K channels open, restoring resting conditions.
Depolarization of excitable membranes triggers an AP only when the membrane potential
exceeds a threshold potential.
Regardless of the size of the stimulus, if the membrane reaches threshold, the AP generated is
the same size.
A membrane is refractory for a brief time following an AP.
APs are propagated without any change in size from one site to another along a membrane.
In myelinated nerve fibers, APs are regenerated at the nodes of Ranvier in saltatory
conduction.
APs can be triggered by depolarizing graded potentials in sensory neurons, at synapses, or in
some cells by pacemaker potentials.
37
what is synapse
“Synapse is an anatomically specialized junction between two
neurons, at which the electrical activity in a presynaptic neuron influences
the electrical activity of a postsynaptic neuron”.
Estimated number in CNS 1014 (100 trillion)
Convergence allows information from many sources to influence a cell’s
activity; divergence allows one cell to affect multiple pathways.
38
types of synapse
Types: Excitatory synapse & inhibitory synapse
Excitatory synapse brings the membrane of the postsynaptic cell closer to
threshold.
Inhibitory synapse prevents the postsynaptic cell from approaching threshold
by hyperpolarizing or stabilizing the membrane potential.
Whether a postsynaptic cell fires action potentials depends on the number
of synapses that are active and whether they are excitatory or inhibitory.
39
electrical synapse
Electrical synapses consist of gap junctions that allow current
to flow between adjacent cells.
The current flows directly across the junction through the connecting
channels from one neuron to the other.
Communication between cells via electrical synapses is extremely rapid
Rare in the adult mammalian nervous system
Possibly involved in functions like synchronization of electrical activity
of neurons clustered in local CNS networks and communication
between glial cells and neurons
Multiple isoforms of gap-junction proteins have been described, and the
conductance of some of these is modulated by factors such as
membrane voltage, intracellular pH, and Ca2+concentration
40
chemical synapse
Chemical synapses, neurotransmitter molecules are stored in synaptic vesicles in the
presynaptic axon terminal, and when released transmit the signal from a presynaptic to a
postsynaptic neuron.
The axon of the presynaptic neuron ends the axon terminal, which holds the synaptic vesicles
that contain neurotransmitter molecules.
The postsynaptic membrane adjacent to the axon terminal has a high density of membrane
proteins that make up a specialized area called the postsynaptic density .
The size and shape of the presynaptic and postsynaptic elements can vary greatly ( Figure
6.26b ).
A 10-20 nm extracellular space, the synaptic cleft , separates the presynaptic and
postsynaptic neurons and prevents direct propagation of the current from the presynaptic
neuron to the postsynaptic cell.
Instead, signals are transmitted across the synaptic cleft by means of a chemical
messenger—a neurotransmitter—released from the presynaptic axon terminal.
Sometimes more than one neurotransmitter may be simultaneously released from an axon, in
which case the additional neurotransmitter is called a co-transmitter .
These neurotransmitters have different receptors on the postsynaptic cell.
41
mechanism of synapse release
Depolarization of the axon terminal increases the Ca+2 concentration within the
terminal, which causes the release of neurotransmitter into the synaptic cleft.
Calcium ions activate processes that lead to the fusion of docked vesicles with the
synaptic terminal membrane
The neurotransmitters are stored in small vesicles, many vesicles are docked on the
presynaptic membrane at release regions known as active zones while others are
dispersed
The vesicles are docked in the active zones by the interaction of a group of proteins,
some of which are anchored in the vesicle membrane and others that are found in the
membrane of the terminal. These are collectively known as SNARE proteins (soluble
N-ethylmaleimide-sensitive factor attachment protein receptors).
The axone terminal have voltage gated channels
The entered Ca interact with separate family of proteins associated with the vesicle,
synaptotagmins , triggering a conformational change in the SNARE complex that
leads to membrane fusion and neurotransmitter release.
The neurotransmitter diffuses across the synaptic cleft and binds to receptors on the
postsynaptic cell; the activated receptors usually open ion channels.
42
activation of post-synaptic cell
Fraction of neurotransmitters are released from the presynaptic axon
terminal bind to receptors on the plasma membrane of the
postsynaptic cell.
The activated receptors themselves may be ion channels (ionotropic
receptors) or may act indirectly on separate ion channels through a
G protein and/or a second messenger (metabotropic receptors)
Opening or closing of specific ion channels in the postsynaptic
plasma membrane change the membrane potential
Due to involved sequence of events, a very brief synaptic delay
—about 0.2 msec—between the arrival of an action potential at a
presynaptic terminal and the membrane potential changes in the
postsynaptic cell occur.
Neurotransmitter binding to the receptor is a transient and
reversible, non-covalent event
43
unbound neurotransmitters are removed from synaptic cleft when they
Unbound neurotransmitters are removed from the synaptic
cleft when they
Neurotransmitter reuptake: actively transported back into
the presynaptic axon terminal
Diffuse away from the receptor site
Neurotransmitter Degradation: enzymatically
transformed into inactive substances, some of which are
transported back into the presynaptic axon terminal for
reuse.
44
types of chemical synapse
According to effects of the neurotransmitter on the
postsynaptic cell, chemical synapses are differentiated in
two types—excitatory and inhibitory
Depends on the type of ion channel influenced, when
neurotransmitter binds to its receptor
45
excitatory chemical synapse
At an excitatory synapse, the electrical response in the
postsynaptic cell is called an excitatory postsynaptic
potential (EPSP).
Usually at an excitatory synapse, channels in the
postsynaptic cell that are permeable to Na+, K+, and other
small positive ions open, but Na+ flux dominates, because
it has the largest electrochemical gradient.
46
inhibitory chemical synapse
At inhibitory synapses, it is either an inhibitory
postsynaptic potential (IPSP) or a stabilization of the
membrane potential near resting levels.
At inhibitory synapses, channels like Cl- or K+ get open
47
synaptic integration
Action potentials are generally initiated by the temporal and spatial
summation of many EPSPs.
A depolarization of the membrane toward threshold occurs when
excitatory synaptic input predominates, and either a
hyperpolarization or stabilization occurs when inhibitory input
predominates.
Assume there are three synaptic inputs to the postsynaptic cell. The
synapses from axons A and B are excitatory, and the synapse from
axon C is inhibitory.
Temporal summation
Spatial summation
The postsynaptic cell’s membrane potential is the result of temporal
and spatial summation of the EPSPs and IPSPs at the many active
excitatory and inhibitory synapses on the cell.
48
synaptic strength
The synapse—whether excitatory or inhibitory—shows enormous variability in the
postsynaptic potentials (strength) that follow a presynaptic input.
The effectiveness or strength of a given synapse is influenced by both presynaptic
and postsynaptic mechanisms.
49
presynaptic mehcanism
Presynaptic mechanisms:
Presynaptic terminal does not release a constant amount of neurotransmitter every
time it is activated
Due to variation in Ca concentration
The neurotransmitter output of some presynaptic terminals is also altered by activation
of membrane receptors on the terminals themselves (as in axo–axonic synapse)
Presynaptic inhibition: Decrease release neurotransmitter
presynaptic facilitation: Increase it
Presynaptic receptors are activated by neurotransmitters or other chemical messengers
released by nearby neurons or glia or even by the axon terminal itself
(autoreceptors: regulate neurotransmer release by feedback mechanism)
50
postsynaptic mechanism
Postsynaptic mechanisms:
Different receptor types for each neurotransmitter operate
by different signal transduction mechanisms and can have
different—sometimes even opposite
Number of receptors for neurotransmitter is not constant,
varying with up- and down-regulation
Ability of a given receptor to respond to its
neurotransmitter can change (receptor desensitization)
Effect of cotransmitter (or several cotransmitters) is
released with the neurotransmitter
51
Modification of Synaptic Transmission
by Drugs and Disease
Therapeutics (recreational) drugs that act on the nervous
system do so by altering synaptic mechanisms and thus
synaptic strength
Interfering with or stimulating normal processes in the
neuron involved in neurotransmitter synthesis, storage,
and release, and in receptor activation.
52
diseases can also affect synaptic mechanism
Diseases can also affect synaptic mechanisms
For example:
Tetanus (caused by the bacillus Clostridium tetani, which
produces a toxin ( tetanus toxin ). Symptoms are increase
in muscle contraction and a rigid, or spastic paralysis
Tetanus toxin is a protease that destroys SNARE proteins,
inhibiting neurotransmitter release
Specifically affects inhibitory neurons in the CNS that
normally are important in suppressing the neurons that
lead to skeletal muscle activation
53
neurotransmistters/neuromodulators
In general, neurotransmitters cause EPSPs and IPSPs, and
neuromodulators cause, via second messengers, more
complex metabolic effects in the postsynaptic cell.
The actions of neurotransmitters are usually faster than
those of neuromodulators.
A substance can act as a neurotransmitter at one type of
receptor and as a neuromodulator at another.a
54
aceytylcholine
Major neurotransmitter in the PNS at the neuromuscular
junction (Chapter 9) and in the brain
Neurons that release ACh are called cholinergic neurons
Cholinergic neurons bodies are confined to few brain
areas but axons are distributed widely
55
aceytylcholine detail
Synthesis: synthesized from choline and acetyl coenzyme A in the
cytoplasm
Storage: stored in synaptic vesicles in presynaptic terminals
Release: Released and activates receptors on the postsynaptic
membrane
Fate:
1) Degradation by enzyme acetylcholinesterase to choline (reuptake
and reutilization) and acetate
2) Simple diffusion away from the synapse to blood which is then
degraded by an enzyme
[Note: nerve gas Sarin block acetylcholinesterase results in
uncontrolled muscle contraction and then receptor desensitization
and paralysis]
56
nicotinic recptor for aceytl choline
Nicotinic receptor:
Responds to alkaloid nicotine(1-2% in tobacco)
Nicotinic acetylcholine receptor is ionotropic receptor (Na/k
channel)
Situated in neuromuscular junctions (blocking lead to paralysis)
and brain (role in cognitive functions and behavior.
For example: One cholinergic system that employs nicotinic
receptors plays a major role in attention, learning, and memory
by reinforcing the ability to detect and respond to meaningful
stimuli
Presence of nicotinic receptors on presynaptic terminals in
reward pathways of the brain explains why tobacco products are
among the most highly addictive substances known.
57
muscaranic
2) Muscaranic receptor
Responds to muscarinic (mushroom poison)
Receptors couple with G proteins, which then alter the
activity of a number of different enzymes and ion channels
Situated in brain and major division of PNS innervates
peripheral glands and organs, like salivary glands and the
heart.
Atropine is an antagonist of muscarinic receptors which is
used dilation of the pupils for an eye exam.
58
alzhiemer disease
Alzheimer disease: Neurons associated with the ACh system
degenerate associated with a decreased amount of ACh in certain
areas of the brain and even the loss of the postsynaptic neurons that
would have responded to it
Prevalence is 10% to 15% of people over age 65, and 50% of people
over age 85
Characterized by declining language and perceptual abilities,
confusion, and memory loss
Genetic cause:
Mutation in genes on chromosome 1, 14, and 21 are associated with
abnormally increased concentrations of beta-amyloid protein
(responsible for cell death)
Mutation in genes on chromosome 19 that codes for a protein involved
in carrying cholesterol in the bloodstream
59
biological amines
The biogenic amines are small, charged molecules that are
synthesized from amino acids and contain an amino group
(R—NH 2 )
It includes
Dopamine
Norepinephrine
Serotonin
Histamine
Epinephrine, another biogenic amine, is not a common
neurotransmitter in the CNS but is the major hormone secreted
by the adrenal medulla.
60
catecholamines
Dopamine , norepinephrine (NE) , and epinephrine all
contain a catechol ring (a six-carbon ring with two
adjacent hydroxyl groups) and an amine group, which is
why they are called catecholamines
61
fate of catecholamine
Actively transports the catecholamine back into the axon
terminal
Broken down in both the extracellular fluid and the axon terminal
by enzymes such as monoamine oxidase (MAO)
[Note: MAO inhibitors increase the amount of norepinephrine
and dopamine in a synapse by slowing their metabolic
degradation. They are used in the treatment of mood disorders
such as some types of depression]
62
location of cadecholine
Location: The cell bodies of neurons lie brainstem and
hypothalamus in brain, few in number and axons extends to
almost all parts of brain
These neurotransmitters play a vital role in states of
consciousness, mood, motivation, directed attention,
movement, blood pressure regulation, and hormone release
Adrenaline: [epinephrine and norepinephrine]
63
receptors of cadecholine
Receptors: There are two major classes of receptors for
norepinephrine and epinephrine: alpha-adrenergic receptors
(α1, α2) and beta-adrenergic receptors.
All catecholamine receptors are metabotropic, and thus use
second messengers to transfer a signal
Beta-adrenoceptors act via stimulatory G proteins to
increase cAMP in the postsynaptic cell. There are three
subclasses of beta-receptors, (β1, β2, β3) , which function
in different ways in different tissues
They act presynaptically to inhibit norepinephrine release
(α2) or postsynaptically to either stimulate or inhibit the
activity of different types of K channels (α1).
64
seretonin
5-hydroxytryptamine, or 5-HT) is an important biogenic amine,
produced from tryptophan
Slow onset of action, therefore works as a neuromodulator.
Serotonergic neurons innervate virtually every structure in the
brain and spinal cord and operate via at least 16 different
receptor types.
Excitatory effect on pathways that are involved in the control
of muscles, and an inhibitory effect on pathways that mediate
sensations.
They contribute to motor activity and sleep, serotonergic
pathways also function in the regulation of food intake, bone
remodeling, reproductive behavior, and emotional states such
as mood and anxiety.
Cont.
Selective serotonin reuptake inhibitors such as paroxetine
(Paxil) are thought to aid in the treatment of depression by
inactivating the 5-HT transporter and increasing the
synaptic concentration of the neurotransmitter.
The drug lysergic acid diethylamide ( LSD ) stimulates the
5-HT 2A subtype of serotonin receptor and alters its
interaction with glutamate receptors in the brain.
Produces the intense visual hallucinations that are
produced by ingestion of LSD
65
amido acid neurotransmitter
Several amino acids themselves function a
neurotransmitters
The most prevalent neurotransmitters in the CNS, and they
affect virtually all neurons
Types:
Excitatory amino acids e.g., aspartate, glutamate.
Inhibitory amino acids e.g., GABA, glycine.
66
glutamate
Primary neurotransmitter at 50% of excitatory synapses in
the CNS
Receptors: majority are ionotropic, although metabotropic
also exist, two important subtypes are
AMPA (α -amino-3 hydroxy-5 methyl-4 isoxazole
propionic acid)
NMDA receptors (bind N -methyl- D -aspartate).
Cooperative activity of AMPA and NMDA receptors has
been implicated in phenomena called long-term
potentiation (LTP).
67
mechanism of LTP
Mechanism of LTP:
Step 1: presynaptic neuron fires action potentials
Step 2: glutamate is released from presynaptic terminals
Step 3: binds to both AMPA and NMDA receptors on postsynaptic
membranes
Step 4: AMPA receptors function just like the excitatory postsynaptic
receptors, the channel becomes permeable to both Na+ and K+, but the
larger entry of Na+ creates a depolarizing EPSP
Step 5: NMDA- receptor channels mediate a substantial Ca2+ flux. A
magnesium ion blocks NMDA channels when the membrane voltage is
near the negative resting potential, and to drive it out of the way the
membrane must be significantly depolarized by the current through AMPA
channels
Step 6: When the depolarization is sufficient, however,
NMDA receptors do open, allowing Ca2+to enter the
postsynaptic cell.
Step 7: Calcium ions then activate a second-messenger
cascade in the postsynaptic cell that includes persistent
activation of multiple different protein kinases, stimulation
of gene expression and protein synthesis, and ultimately a
long-lasting increase in the sensitivity of the postsynaptic
neuron to glutamate
68
GABA
Major inhibitory neurotransmitter in the brain derived from
glutamate.
GABA neurons in the brain are small interneurons that dampen
activity within neural circuits.
Postsynaptically, GABA may bind to ionotropic or
metabotropic receptors
The ionotropic receptor increases Cl- flux into the cell,
resulting in hyperpolarization of the postsynaptic membrane. In
addition to the GABA binding site, this receptor has several
additional binding sites for other compounds, including
steroids, barbiturates, and benzodiazepines to reduce anxiety,
guard against seizures, and induce sleep.
69
mechanism of GABA
Mechanism: Ethanol stimulates GABA synapses and simultaneously
inhibits excitatory glutamate synapses, with the overall effect being global
depression of the electrical activity of the brain.
70
characteristics of alcoholics as dose increases
Characteristic of alcohlics as dose increases:
Reduction in overall cognitive ability, along with sensory perception
inhibition (hearing and balance) loss of motor coordination, impaired
judgment, memory loss, and unconsciousness.
Suppression of brainstem centers responsible for regulating the
cardiovascular and respiratory systems
Dopaminergic and endogenous opioid signaling pathways (discussed in the
next section) are also affected by ethanol, which results in short-term mood
elevation or euphoria.
71
Glycine
Major neurotransmitter released from inhibitory interneurons
in the spinal cord and brainstem
Binds to ionotropic receptors on postsynaptic cells that allow
Cl- to enter leading to hyperpolarization.
Maintain a balance of excitatory and inhibitory activity in
spinal cord integrating centers that regulate skeletal muscle
contraction
Neurotoxin strychnine , an antagonist of glycine receptors
sometimes used to kill rodents. Victims experience
hyperexcitability throughout the nervous system, which leads
to convulsions, spastic contraction of skeletal muscles, and
ultimately death due to impairment of the muscles of
respiration
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neuropeptides
The neuropeptides are composed of two or more amino acids
linked together by peptide bonds.
About 100 neuropeptides have been identified, but their
physiological roles are not all known.
Synthesis: as other proteins
Neurons that release one or more of the peptide
neurotransmitters are collectively called peptidergic
After release, peptides can interact with either ionotropic or
metabotropic receptors.
They are eventually broken down by peptidases located in
neuronal membranes.
A group of neuropeptides (endogenous opioids) that
includes beta-endorphin , the dynorphins , and the
enkephalins —have attracted much interest because their
receptors are the sites of action of opiate drugs such as
morphine and codeine .
Play a role in regulating pain
Substance P , another of the neuropeptides, is a
transmitter released by afferent neurons that relay sensory
information into the CNS. It is known to be involved in
pain sensation
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gases
Certain very short-lived gases also serve as neurotransmitters [ Such as
Nitric oxide, carbon monoxide and hydrogen sulfide]
Produced by enzymes in axon terminals (in response to Ca entry) and
simply diffuse from their sites of origin in one cell into the intracellular
fluid of other neurons or effector cells, where they bind to and activate
proteins.
For example, nitric oxide released from neurons activates guanylyl cyclase
in recipient cells, which increases the concentration of the
second-messenger cyclic GMP.
Nitric oxide plays a role in a bewildering array of neutrally mediated
events—learning, development, drug tolerance, penile and clitoral erection,
and sensory and motor modulation, to name a few.
Paradoxically, it is also implicated in neural damage that results, for
example, from the stoppage of blood flow to the brain or from a head
injury.
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purines
Other nontraditional neurotransmitters include the purines,
ATP and adenosine , which act principally as
neuromodulators.
ATP is present in all presynaptic vesicles and is coreleased
with one or more other neurotransmitters in response to Ca
influx into the terminal.
Adenosine is derived from ATP via enzyme activity occurring
in the extracellular compartment. Both presynaptic and
postsynaptic receptors have been described for adenosine, and
the roles these substances play in the nervous system and other
tissues are active areas of research.
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