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01/01/2001
Introduction to Neuroscience
Early Days
Gross Anatomy of the Brain
Origins of Neuroscience
Neurons and Glia
Classifying Neurons
Case Study (Mental Retardation, Alzheimers)
The study of the Central Nervous System (CNS) and the Peripheral Nervous
system (PNS).
1. Early Days
People believed that head aches or other forms of pain in the head
was due to bad spirits that were trapped inside the brain. To remove
them, a surgical skull procedure called Trepanation was conducted.
This appeared prominent in human remains from the past
s
Gryi are the folds in the brain or the risen parts of the brain whilst the
Sulci are the grooves or depressions on the brain
(The image to the right is fissures of the skin which are a form of
deep sulci)
[3. Origins of Neuroscience]
Nerves as wires
Different parts of the brain for different functions
Evolution of the Nervous System
The Basic Functional Unit: The Neuron
Dendrites
Soma
Axon
Astrocyte Cell
Neuronal Cell
Oligodendrocyte
Cell
Microglial Cell
Glial Cells
Ependymal Cells: Surround and make the membrane of the brain.
They are commonly known to be involved in making the spinal fuid
inside the ventricles of the brain.
Oligodendrocytes (CNS) : Insulate the neurons axon with myelin to
allow faster transmission signals.
Astrocytes : Surround blood vessels and neurons to supply rich
nutrients to the neuron and surrounding cells.
Microglia: Are the white cells of the brain which protect the neurons
from infection/virus.
Schwann Cells (PNS): Not to be confused with Oligodendrocytes, as they
perform a similar role to insulating neurons with myelin but ONLY in the
peripheral nervous system.
Neuronal Cells
1. Nucleus (DNA)
RNA Transcription
DNA Replication
Gene Expression
2. Soma (Body of the Cell)
Rough ER (Ribosomes)
o mRNA translation
o Protein Synthesis
Golgi Apparatus
o Final assembly of protein and packaging
Smooth ER
o Several Metabolic Processes (production of steroids, lipids..)
Mitochondria (Cellular Respiration)
o ATP manufacturing site
o Glucose Pyruvate ADP ATP
3. Neuronal Membrane
Phospholipid Bi-layer, usually varying in protein richness.
4. Cytoskeleton (Non-Static)
The Bones of the neuron cell, providing a sturdy structure to
maintain shape and function within the cell.
6. The Axon
What
7. Synapse
Where the Synaptic Gap is located
Action potential (electrical) signal is converted in chemical signal
Release site of Neurotransmitters
Link between Axons and Dendrites
8. Dendrites
Antennas of the Neurons
Incoming signals from other surrounding cells.
[5. Classifying Neurons]
Uni
Classification by Morphology
-polar
Bipolar
Multi-polar
Classification on CNS
Primary Sensory Neurons
Primary Motor Neurons
Interneurons (between neurons)
Further Classification
Based on Axon Length
o Golgi Type 1
o Golgi Type 2
Based on Neurotransmitter Type
o Cholinergic = Acetylcholine
Extra Terminology
-cyte : Denoting a mature cell lymphocyte, astrocyte
-blast : Denoting a embryonic cell osteoblast
[5.Case Study]
Alzheimers Disease
Alzheimers Disease is the slow degeneration of the human brain.
Alzheimer discovered after dissecting a womans brain who showed signs of
memory loss, loss of cognition, deliriousness and confusion that 1/3 of the
neuron cells within her brain had died. Leaving practically nothing of the cell
but the remains of the cytoskeleton.
Mental Retardation
Mental retardation is considered when the IQ of a person is below the
standardized intelligence of <70 are considered mentally retardation. The Bell
shape curved that distributes the population has a mean of 100.
So what is Mental Retardation exactly?
There are many causes to the mental retardation that branch off into
different conditions. The basis of mental retardation is the when the brain is
affected during development and is unable to develop to its full potential.
Neurons in mentally retarded patients have been seen to contain less dendrites
surrounding the neuron and also the structure of the dendrites. It has been
shown in research that the dendrites of mentally retarded patients contain
abnormal structures and tend to usually long and skinny. This structure has
shown to be very similar to the structure of neurons of a fetus.
What are the causes?
There are a wide range of causes in mental retardation but most of them can
be linked to the early stages of development. One condition is known as
Down Syndrome, where one extra chromosome is found on chromosome 21
and directly affects the development of the brain. Another cause is due to the
malnutrition of the fetus during development. This can be causes due to
common correlations such as drug use, alcoholism in mothers. Another
severe form of mental retardation is formed from a genetic disorder known
as PKU (Phenylketonuria) where the amino acid known as phenylalanine is
over produced in the liver. High concentration of phenylalanine stunts the
growth of the brain. Thankfully, if detected early during development some
of these conditions can be reversed and allow full development of a healthy
brain .
Down Syndrome (Extra chromosome on C 21)
Malnutrition during pregnancy
PKU (Over production of Phenylanaline)
Na+
and
K+
Na+ and K+ are the main players that form a concentration gradient
across the cell membrane. Due to the simple law of Diffusion we
know that an area of high concentration wants to diffuse to an area of
low concentration.
In cells, there is a high concentration of potassium K+ and a low
concentration of sodium Na+. Visa versa, there is a high concentration
of Na+ outside the cell and also a low concentration of K+. Intern this
forms a concentration gradient.
Sodium really, really wants to go inside the cell!
Potassium really, really wants to leave the cell!
The role of the semi-permeable membrane stops this. Although there
are leaky ion channels that tend to allow a small flow of ions these
ions in and out of the cell. The cell membrane is more permeable to
K+ rather than Na+.
What forms the actually difference in charges across the cell
membrane?
Intracellular side of the cell has many more proteins that are negatively
charge. Leaving the intracellular cell overall negative (Vm: -65mV)
These proteins tend to form around the cell membrane causing like
charges to attract. Na+ and K+ tend to huddle around the perimeter of
the cell membrane due to the membrane potential.
Further factors contributing to the huddling of charges across the
membrane are led back to leaky ion channels. K+ tend to leak out of
the cell much more than Na+. Intern leaving the cell gradually more
negative and the outside more positive. Creating more of a potential
difference across the cell membrane.
OVERALL when these factors are all placed together we reach a equilibrium
state. This causes the resting cell membrane potential!!! And is attributed to
by a Electro-Chemical Gradient as both a combination of concentration
gradient and electrical gradient (like charges attract) are involved.
2.
MEMBRANE
is now polarized and
has the POTENTIAL to
create a sudden movement of ions across this membrane, but it is
currently in a state of REST or equilibrium.
RESTING CELL MEMBRANE POTENTIAL
Modeling Resting Cell Membrane Potential
Em =
particular
that is permeable.
Ek
or ENa as an example.
3 Na+ out 2 K+ in
The signal does not grow weaker and propagates effectively from
neuron to neuron.
The Action Potential Steps
1. A form of stimulus comes along and causes a channel to open. Examples
include neurotransmitters that connect to chemically gated proteins, a
stretch in the cell membrane (Mechanoreceptors).
2. If the stimulus is effective and triggers above threshold (-55mV) it will
cause a dramatic change within the membrane potential, voltage gated
Na+ channels will now open in response.
3. Na+ voltage gated channels open and depolarize the cell, making it
more positive. The cell is stimulated and the signal is propagated
throughout the cell.
4. Na+ channels close and K+ voltage gated proteins open. K+ flows
down its electrochemical gradient. This is known as repolarization as the
cell loses it positivity and approaches back to a negative cell membrane
potential.
5. K+ voltage gated channels tend to be slow and sluggish and remain open
a tiny bit longer than Na+ channels. This causes the cell to hyperpolarize
or become more negatively charged in comparison to the resting
membrane potential.
6. Na+/K+ pump and Leaky channels work together to restore the resting
membrane potential. Ions flow down back their concentration gradients
and the Na+/K+ pump maintains the resting cell membrane potential.
Rate = 100m/sec
Continuous Conduction (Minority)
Continuous conduction involves no myelin sheath (un-myelinated)
around the axonal membrane. They propagate down the axon via a
continuous amount of Na+ and K+ channels down the length of the
axon. It is considered much slower than Saltatory Conduction.
Rate = 10m/sec
What influences the rate of conduction?
The Diameter of the Axon Larger axons conduct faster
Myelinated or Un-myelinated eg: Saltatory or Continuous
Temperature Rate is significantly decreased in colder temperatures
Answer
A) No net movement as the cell is in a equilibrium state with the K+.
K+Inside = K+Outside
B) K+ will move to the extracellular matrix due to the concentration and
electrical gradient.
C) K+ will move to the intracellular matrix.
Electrical Synapses are also known as gap junctions. They are cells
in which they are connected via protein channels called connexins
which make up a connexon. Two connexons join from each cell
membrane connect the cells and allow ions to pass through
bidirectional.
Gap Junctions allow cells to communicate in a cascade fashion and
synchronized harmony. A PSP (Post Synaptic Potential) allows these
cells to integrate and simultaneously depolarize. Eg: Cardiac cells
within the heart.
Chemical Synapses
The most abundant type of synapse are chemical synapses which are
found in CNS and PNS.
Pre-synaptic Element:
The presynaptic element is where neurotransmitters are stored in vesicle
structures. The presynaptic contains the active zone where vesicles fuse with the
membrane and release the messengers into the synaptic cleft.
Membrane differentiations
Active Zone: Where the neurotransmitter vesicles + Ca2+ channels are
found.
Synaptic Density: Where a concentration of receptors reside.
Synaptic Vesicles
The vesicle structures that concentration neurotransmitters into a little ball
which fuses with the pre-synaptic membrane to then be released
Receptors
Neurotransmitters bind to the receptors found on the postsynaptic density.
Post- Synaptic Element
Action potential causes the release of a neurotransmitter from the presynaptic
element to the post synaptic element where the information is interpreted.
Geometry of Synapses
Axodendritic:
Axon connected to dendrite
Axosomatic:
Axon connected to the soma of the cell
Axoaxonic:
Axon connected to another axon
Dendrodendrictic : Dendrite to dendrite
CNS Geometry
Grays I (asymmetrical)
Excitatory synapse
Grays II (symmetrical)
Inhibitory synapse
The NMJ is the biggest synapse in the body and is the most studied
and understood synapse. Ach is the neurotransmitter released by the
pre-synaptic element which is funneled from the active zone to these
folds at the junction.
Neuropharmacology is profoundly focused on these synapses as many
toxins are able to block the receptors for Ach and intern cause
muscular paralysis.
2. Principles of Chemical Synaptic Transmission
1. Neurotransmitters (amines, amino acids and peptides) are synthesized
either at ER or onsite at the pre-synaptic element.
2. Neurotransmitters are packaged into vesicle structures and await
deportation at the active zone.
3. Action Potential causes the depolarization of the cell in which
reaches the pre-synapse and causes Ca2+ to open.
4. Vesicles fuse with the active zone and are released into the synaptic
cleft.
5. Neurotransmitters attach to receptors on the post-synaptic density
area and cause electro/chemical response to post-synaptic cell.
Neurotransmitter Receptors
POST-SYNAPTIC
MEMBRANE
Ionotropic
VERY FAST TRANSMISSION
Spans the width of the post-synaptic membrane
Opens by stimulation of neurotransmitter
Unlike Na+ and K+ voltage gated channels as it
allows both Na and K to flow in, it is not as specific.
Stimulates both IPSP and EPSP
Metabotropic (G proteins)
Metabotropic Receptor
(Metabo = Metabolic)
SLOWER/LASTING
TRANSMISSION in the
POST SYNAPTIC
NEURON
Metabotropic have more
diverse functions in
comparison to Ionotropic
receptors.
They are activated by a
specific neurotransmitter
(1st Messenger) and are
linked to a
GProtein which can open a ion
channel or
produce a 2nd Messenger (cAMP)
that can run off into the cytosol and cause a cascade of effects.
EPSP and IPSP
We can evaluate that much like a leaky hose, the water that runs from the source
to the end will be much less or non at all due to the leaks. This is how some
dendrites function.
Dendritic length constant ()
The dendritic length constant, mathematically shows how the depolarization at a
dendrite exponentially decreases over distance. As when a the post-synaptic
membrane potential will propagate towards the axon hillock but if the signal
is too weak when it reaches, it will not cause a action potential.
Excitable Dendrites
Some dendrites have characteristics in a way they are more
excitable. Passive dendrites will receive a signal from a presynaptic neurotransmitter and transfer the signal along the inside the
cell, but as we know it exponentially will decay if a weak signal.
Active Dendrites contain voltage gated ion channels such as K, Na
and Ca2+ to allow them to amplify the signal and intern increase the
chances of a AP.
This also allows a signal to travel along in the other direction, from
the soma, along a dendrite and to a axon. This is to inform the
neighboring cell that a spike has occurred in the soma and is a key
property in learning.
MORE OPTIONS
The NT norepinephrine attached to the norepinephrine receptor
(G-protein).
1. The G-protein located intracellular is activated to stimulate Adenylyl
cyclase (Enzyme) that dephosphorylates ATP to cAMP a secondary
messenger that can diffuse off into cytosol to create a cascade of effects.
2. In the context of the norepinephrine receptor, the cAMP runs off to
find a protein kinase (on/off) that phosphorylates the K+ channel to
change its conformation and CLOSE.
3. The closing of the potassium channel increases the excitability of the
cell (as no K+ is leaking out) and therefore increases to chance of the cell
to depolarize.
1st Messenger: Norepinephrine (Neurotransmitter)
2nd Messenger: cAMP
G proteins are not channels as you can see when theyre activated they
do not open. They can indirectly open a channel or produce a 2nd
Messenger to cause a cascade of effects within the cell.
Neurotransmitters Lecture 4
Neurons must synthesize and store the neurotransmitter within the cell
Neurotransmitter must be released at the axon terminal when
stimulated.
Neurotransmitter must bind to a receptor protein in the post synaptic
element.
Degradation of Neurotransmitter (recycled).
DALES PRINCIPLE
One neurotransmitter, one neuron. Usually neurons synthesis one
type of neurotransmitter and secrete one type of transmitter. Cofactors are a
exception. (Peptide + amino acid)
Estimated 107 (Billions) Neurons and 1014 (Trillion) Synapses in the
human body Explains their diverse functions and range
How do we identify a Chemical as a neurotransmitter?
If there is a hunch a chemical might be a neurotransmitter a scientist can
perform the following to find the proof.
Immunocytochemistry
Reacting a anti-body to bind to the chemical to find where in the cells the
chemical is.
In Vitro Brain slices
Bathing particular segments of the brain in solution and stimulating it to
see what chemical is released into the solution.
In situ Hybridization
Complementory mRNA to attach itself to ssRNA used to synthesize the
chemical or receptor.
Microionophoresis
Selecting a compound that mimics the theorized neurotransmitter and
seeing if it attaches to the same receptors.
(nicotine/muscarine mimic Ach neurotransmitter)
Neuropharmacological Analysis
Using drugs on specific synapses to see their effects on the receptors. Eg:
Curare is a agonist of nicotinic receptors, causing paralysis .
Ligand Binding
The use of a radioactive isotope to bind to a ligand molecule
(neurotransmitter) to see where it attaches onto what receptors.
synaptic
(AchE).
motor
and has
muscle
effect and
in the
Catecholaminergic Neurons
The Catecholamines are derived from the precursor and amino acid
Tyrosine and all contain chemical group called a Catechol. Catecholamines
include
Dopamine
Norepinephrine
Epinephrine
Catecholamines are important in the regulation of movement, mood
(reward), attention and visceral function (ANS)
Catechol + amine = Catecholamine
Tyrosine (TH) is the derivative of all the Catecholamines that is, it is the
precursor to form Tyrosine Dopamine Norepinephrine Epinephrine
Tyrosine Dopamine
Dopamine is a major neurotransmitter is the CNS for the control of mood
in terms of rewarding mood behaviors and in motor control. A common
degenerative disease called Parkinsons Disease is due to the degeneration of
Dopaminergic neurons. Treatment includes using Dopa enzyme to increase the
levels of Dopamine within the remaining dopaminergic neurons.
Symptoms of Parkinsons is shown in shaking motor control or tremors.
release
diet.
Serotonin made in two steps
Tryptophan(TP) (Tryptophan
1.
Hydroxylase) 5 -HTP
2.
Serotonin
5-HTP
(5 HTP Carboxylase)
AMPA Glutamate binds to AMPA that allows both K+ and Na+ to pass
through, therefore creating a rapid depolarization.
NMDA Requires Glutamate + Glycine to bind to but also the removal of
Mg++ that clogs the pore of the ion channel. Mg++ (the bouncer at the night
club) doesnt allows any of the permeable ions to flow through which are Ca++
and Na+.
Only depolarization of the membrane will unbind Mg++ by losing its affinity
from the pore and allow Na and Ca++ to flow through.
(NMDA channels are linked to long term memory)
AMPA Binds Glutamate Na+ into post synapse Fast
Depolarization
NMDA Blinds Glutamate Mg++ blocks and becomes voltage
dependent
G
The beauty of neurotransmitters is that they can change from one major
excitatory NT such as Glutamate (EPSP) to a major inhibitory NT GABA
(IPSP) in one step. GAD enzyme transforms Glutamate GABA
G Proteins are named by the energy molecule that they utilize, GDP which is
a derivative of ATP and when activated by its particular NT, goes from GDP
GTP and causes the G-Protein to split and activate subsequent proteins
downstream or effectors. The shortcut pathway of G-protein is that it doesnt
have many intermediates for it to start working, enabling it to work faster. The
major difference between G-Proteins and ionotropic ligand gated channels is
that they produce a secondary messenger, usually in the form of GDP that runs
off into the cell and can activate a cascade of events. A common event is that it
can activate Protein Kinases (switch things on/off) that phosphorylate (switch
on) proteins to change their conformational shape eg: ion channel. Protein
Phosphatases are enzymes that switch off the or inhibit the effect of protein
kinases which de-phosphorylate the protein.
Kinases Phosphorylate (switch things on)
Phosphatases
dephosphorylate
(switch things off)
Example
1. NT arrives and attaches to its receptor
2. GDP is exchanged for GTP
3. GTP splits/activates the segments that runs along the Post synaptic
membrane to effectors
4. Section of the G-protein gates a K+ than allow heart rate to reduce.
Are found deep in the dermis layer and look like onions. They have
large receptive field and adapt (stop depolarizing) to sense quickly
Meissners Corpuscle (Dermis) Small Receptive field Rapid
adaption
Are found in the dermis, have a small receptive field and adapt fast
.
Diagram showing the minimum distance needed to discriminate between
two points on the body.
A, A, A and C axons Primary Afferent Neurons
.
Diagam relevant to evoultionary traits, dermatones are linearized
when we get on all fours (like our ancestors)
A single spinal segment consists of the dorsal root (afferent) and
ventral root (efferent) covers an area on the body.
The
communication between the area and spinal
segment is known as a Dermatome.
to
their own
Neglect Syndrome
Where a person neglects a part of
their body or a part of the world. Due
lesions in the areas of the Postier
Parietal Cortex are related to
neglect syndrome. For example a
person might disregard their arm as
arm, or dress only half the body
because they dont believe the other half is
theirs, or neglect everything to the left of
their central vision.
VERY BIZZARE BUT INTERESTING
NEUROLOGICAL DISORDER!!
Hyperalgesia
The increased sensitivity to pain. A regulated mechanism to let us know that that
area (muscle, bone) is damaged or potentially being damaged. The increased
sensitivity of pain is hyperalgesia. In other words, if you poke a person who
has surffered a 3rd degree burn, it fucking hurts.
Substances are released when tissue damage occurs
Nociceptors respond to these
o K+, Bradykinin (directly depolarizes nociceptors)
prostaglandins (by products of enzymatic lipid breakdown),
Histamine (hormone that inflames area) and Substance P
which is produced from the actual nociceptors themselves.
Substance P
A peptide synthesized by C fibres themselves to communicate with other
nociceptors and cause vasodilation of the blood vessels.
Nerve Axons
straight
opposite of
but
1
2nd
3rd
Order : Sensory
Spinal Crd
Order: Spinal Cord Brain
Order: Within the Brain
st
Afferent Regulation
Gate Theory suggests that maybe neurons at the dorsal horns that
project axons up the spinothalamic and neurons that project up the
dorsal column are intercepted by a interneuron.
If large A sensory neurons are a excited they can possibly inhibit the
nociceptive neurons.
Descending Regulation
PAG (Periaqueductal Grey Matter)
Opioids
The compound opium is found in many opioid substances that are
well known for their analgesi, sedative and euphoria effects.
Opium is the active ingredient in a lot of narcotics that are abused
Analogues include morphine, heroin and codeine.
Opioid substances bind tightly to opioid receptors that are originally the
receptors for the bodys own naturally opioid substances to down regulate pain.
Endorphines were found through the use of opioids.
Endorphines (Endogenous Morphine)
Endorphines are found throughout the CNS and relatively small
peptide proteins.
Endorphines are widespreadly used in the body but are well known to
be the bodies natural morphine making compounds that can regulate
nociception
Endorphines systems can block the pre-synaptic terminals of
glutamate and hyperpolarize nociceptors. Intern preventing the
passages of signals ascending to the brain and prevent the perception
of pain.
An itch sensation travels along C fibres towards the brain. C fibres are mainly
concered with itch sensations, temperature and some pain unlike delta fibres
that are more associated with pain. The itch sensation depending on where it
is located will travel through the spinothalamic pathway to the thalamus and
relayed to the somatosensory cortex, assuming that the itch is peripheral and
not on the face. Otherwise, the itch sensation will travel along the trigeminal
pathway through the trigeminal nerves.
2nd Order.
2nd order Neurons synapse the signal from the spine to the brain. 3rd order
neurons are located inside the brain and 1st order are sensory neurons located all
over the skin.
Gustatory (Taste)
Humans have inborn chemical sensations to alert us about something
that could be harmful eg: posions are usually bitter and things that are good for
us eg: sugars (simple carbohydrates) that are sweet
Bitter Poison Reject
Sweet Sugar Accept
Taste Buds
Taste buds are
composed of around 50150 taste cells. These taste cells
are NOT neurons, but they do
synapse onto afferent neuronal
axons that lead off to the
brain.
Tastant Taste Cell
Depolarization onto Gustatory
Afferent AxonsNT released onto
Gustatory Afferent
Axons
Microvilli
form around the taste pore where
the tastants are received and bind to receptors on microvilli.
Basal Cells contribute to regenerating taste cells and secreting
mucous/saliva for the tastants to dissolve into.
The Apical end of the taste cell is a taste pore that is exposed to the
surface of the tongue. Microvilli are surrounding this area so that the
tastants can be detected and attach to the cell receptors.
Taste Transduction
Saltiness Na+ amiloride channel
Sourness H+ blocks K+ channel and uses Na+ amiloride channel
Bitterness (G protein T2Rs)
Sweetness (G protein T1R1 1 and T1R1 2)
Umami (G protein T1R1 and TIRI3)
Saltiness comes from the compound NaCl or things that contain the
ion Na+. It is mostly picked up around the sides of the tongue.
Na+ can directly enter the apical end of the papilla and diffuse
directly across the microvilli through a open Na+ channel. This
channel allows Na+ to flow freely down its concentration gradient into
the taste cells. It is known as the Na+ Amiloride channel.
Taste Cells reach threshold and open Ca2+ and Na+ voltage gated
channels to than release a neurotransmitter to gustatory afferent
axons..
Sourness (H+ influx)
Sourness occurs from H+ ions from acidic
compounds. It is mostly picked up along the sides of the
tongue
H+ ions flow into the apical end and cross the
microvilli of the taste cell from the surface of the
tongue.
H+ use the same Na+ amiloride channel as Na+, but
blocks the K+ channel of the cell, causing it to
depolarize faster and cause Ca2+ and Na+ voltage
gated channels to open.
Neurotransmitter is released to gustatory afferent
axons.
IP3 is sent off into the cytosol and opens Na+ channels to depolarize
and also voltage gated Calcium channels depolarize.
IP3 can also activate intracellular stored Ca2+ that also can depolarize
the cell. Neurotransmitter is released to afferent gustatory afferent
axons.
Taste Pathways
Nerves VII (7), IX(9) and X(10) bundle the gustatory afferent nerves
and terminate in the Solitary Nucleus of the Medulla.
VII Facial Nerve
IX GlossoPharagneal Nerve
X Vagus Nerve
Afferent Gustatory Axons Cranial Nerves VII,IX and X Solitary
Nucleus (Gustatory Nucleus) VMP (thalamus) Gustatory Cortex
Each taste cell is broadly tuned, their responses are combined into
afferent axons and a whole combinations of stimulus can be interpreted. This is
known as population coding, in that a broad range of neuron stimulus is
combined and the brain has a variety of stimulus to interpret.
Olfactory input also contributes as odors can stimulate and combine
with the taste along with the texture and feel of the food.
Olfactory Smell
Smell or our olfactory system is to help us distinguish and warn us
about good substances and bad substances .
Olfaction is associated with gustatory and provides us is with a more
thorough sensory detection mechanism.
3 Types of Cells
Olfactory Receptor Cells
These cells axons penetrate the cribriform plate and their axons link up
nd
with 2 order neurons called Glomeuri or a Glomerulus. These cells are actual
neurons unlike the taste cells in the gustatory system.
Glial Cells
Glial cells that support and nourish olfactory sensory neurons. They also
produce mucous that odorants dissolve in along the epithelial layer. Mucous
contains antibodies and enzymes to break down pathogens.
Basal Cells
The unique thing about the olfactory system is that contain one of the few
types of neurons that continually renew themselves. Basal Cells, differentiate
into olfactory neuron cells constantly, as the receptor cells are very delicate.
Olfactory Neuronal Cells
One of the few types of neurons that can continually replace
themselves.
Very susceptible to damage, such as a blow to the cribriform plate can
break olfactory neuron cells and cause Anosmia.
Anosmia The inability to smell
Olfactory neurons have dendrites that end at a
knob in the mucous layer. Cilia
project into the mucous layer and are ready to be
depolarized by odorants.
Cilia within the membrane mainly
use a special type of G-Protein.
This G-Protein is known as Ggolf.
Olfactory neurons combine
to the olfactory nerve which bundles
to Cranial Nerve 1
Olfactory Transduction
pathway
1. Ggolf stimulated protein by ordorant
2. Adenyl Cyclase activates 2nd Messenger cAMP
3. cAMP activates cAMP activated channels (unusual)
4. Na+ and Ca++ channels open and depolarize the cell.
5. Cl- channels also open by Ca++ but expel Cl- from the cell causing a
BIG DEPOLARIZATION
6. Cranial 1 Nerve Olfactory Bulb
Population Coding
Similar to Gustation, in that specific populations of neurons that are
broadly tuned to one stimulus to be interpreted by the brain a specific odor. The
combination of this specific stimulus encodes a specific odor and is interpreted
by higher orders of the cerebral cortex. Population coding offers hundreds of
thousands of receptors to be able to discriminate odors, thus giving us a great
range for smell.
Olfactory Maps
The idea that specific neurons are linked to specific glomeruli in a
specific area of the olfactory bulb to interpret a specific odor. Thus, forming a
spatial pattern and contain specific maps or roads that odorants follow
depending on the stimuli nature.
Temporal Coding
The idea that a specific number of spikes or AP sent to olfactory system
and are a form of code for specific odorants. This idea is behind the quality and
concentration of the smell. Does a high conc and pure smell stimulate a specific
number of spikes than a lower quality? Does it code for a specific odor? Does
the timing of the spikes influence factors of the odor and how it is interpreted?
Research is continuing..
Vomeronasal Organ
The idea that pheromones are linked to specific behaviors, emotional
regulation, identifying individuals and sex drive.
The Vomeronasal organ located in the nasal cavity which projects to
the olfactory bulb and to the hypothalamus (hormonal regulation).
It is believed that the vomeronasal organ could be linked to many
social behaviors from pheromones :
o A baby identifying a mother as her mother
o Sexual drive between girl and guy, from sweating and smelling
sex driven pheromones
o Marking individuals territory and expressing dominance
Do pheromones increase sexual behavior in humans? No convicting
evidence as of yet, BUT THERE IS BIG DOLLARS TO WHOEVER
FIGURES IT OUT! $$$$$$$$
Brain Rhythms
EEG Electro-encephalogram is a piece of equipment used to
analyse the rhythms of the brain
Electrodes are evenly distributed over the head, most evident over the
ceberal cortex. These electrodes detect populations of neurons firing
and giving off certain frequencies and amplitudal waves.
EEG is used to analyse the rhythms of patients who suffer from:
o Sleep disorders
o Epilepsy
o Brain Disorders
The EEG Waves (BAT-D)
Beta (>14 Hz) Beta waves are the small high hertz waves that are
associated with high cortical activity such as physical work or mental
work. Alert and awake state.
Alpha(8-13 Hz) Alpha waves are a bit less frequenct than Beta
waves and have a greater amplitude. Associated with relexation and
prominent during eye closure.
Theta (4-7 Hz) Theta waves are associated with sleep states, REM
sleep, drowsiness or hypnotic states. Theta waves also unsually
become prominent when problem solving.
Delta (>4 Hz) Delta waves are the slowest waves and have high
amplitudal waves. They are associated with deep sleep and
drowsiness.
Treatments
Surgeons are known to remove certain parts of the brain where
seizures are most prominent. Parts of the corpus collosum are a typical
area to remove so that the seizures dont spread.
Drugs that increase GABAergic activity known as anticonvulsants
Current Research is in electrode stimulators that can be inserted into
parts of the brain and can restore and monitor normal wave rhythmic
function of the brain. Known as The Pacemaker of the brain.
Identifying lesions within the brain using MEG, fMRI and PET scans
and removing lesion.
The Hypothalamus
Anterior/inferior to the Thalamus is located the Hypothalamus. It is
known as the highest form of endocrine control in the body.
The hypothalamus is responsible for the tight regulation of homeostasis
within the body.
Examples include: pH regulation, oxygen regulation, temperature
regulation, blood pressure and volume regulation, digestion and so on.
The hypothalamus regulates these changes due to change from
environmental stimuli. Such as jumping in a cold pool. The
Hypothalamus would react to the stimulus and secrete a
neurohormone that acts as a chemical messenger and is sent around
the body to draw blood away from the surface and keep the internal
organs at 37 degrees.
The hypothalamus
Connected inferior to the hypothalamus is the pituitary gland.
Pituitary gland is divided into two sections. The anterior lobe and the
posterior lobe.
We are mainly concerned with the periventricular layer of the
hypothalamus that is responsible for the synthesis and excrection of
neurohormones.
baby
Regulates blood
volume (water) and blood salt
levels.
Kidney Liver HT
On top of the kidneys are located the
Renal Medulla and Renal Cortex. The
Kidneys regulate blood composition and water
retention. When the body is lacking water Renin
hormone is released by the Renal Medulla
which activates Angiotensinogen from the
liver. Angiotensinogen forms Angiotensin II
which is a vasoconstrictor to intern increase
and maintain BP. Angiotensin II also
stimulates the Hypothalamus to excrete the
neurohormone Vasopressin (ADH) which
increases the water renention of the kidneys by
taking up more H2O and stimulates the subfornical
organ which intitiates the sensations of thirst
behavior.
Anterior Pituitary Gland
and drinking
.
Parvocelllular neurosecretory cells are located the periventricular
area of the hypothalamus. This time, the anterior pituitary lobe is
actually a gland in that it synthesizes and secretes a multitude of
hormones.
The hypothalamus secretes hypophysiotropic hormones that either
STOP or START the excretion of anterior pituitary cells.
Sympathetic Neurotransmitters
Preganglionic axons in the CNS exit the spinal cord at the thoracic and
lumber regions. They then synapse onto the sympathetic chain which is where
all the ganglion are present.
Pre Ganglionic Acetylcholine
Post Ganglionic Norepinephrine
Parasympathetic Neurotransmitters
Preganglionic axons leave the CNS at the brain stem and at the sacral area of
the spine. Notice that their ganglion are much further away from the spinal
cord and more near the organs they effect. This is why their pre ganglionic
axons are much longer compared to the sympathetic pre ganglionic axons
Pre and Post The pre and post ganglionic neurons are all
acetylcholine baby!
The Enteric System
The enteric system is known the little brain within the ANS as it is
highly independent and can function without too much input from the ANS. It is
a complex and condensed network of neurons throughout the whole
gastrointestinal tract. It is composed of the two layer:
Myenteric layer
Submucous layer
Mental Illness
Anxiety Disorders
Agoraphobia/Panic disorders
OCD
Biological evidence/treatment
Thoughts of suicide
Prolonged exposure to all of these symptoms can therefore be evidence to
diagnose depression. Periods of genuine depression last for months onto years
and patients readily relapse into the condition. It is calculated 50% of patients
left untreated will relapse into major depression and 70% after 2-3 episodes will
relapse also.
Bipolar Disorder
Type I
Type II
Type one bi-polar is usually associated with symptoms of mania
(repetitive fluctuations of euphoria and overexcitement) whilst type two is
associated with as the name implies, the repetitive fluctuations between periods
of mania and periods of depression.
Major depression and Bipolar disorders have been linked to the in balance of
two of the main diffuse modulatory systems within the brain. The in balance of
serotonin levels and norepinephrine levels has been attributed to the diseases.
Two theories of Mood Disorders
Mono-Amine Hypothesis
Depletion or reduction of serotonin an norepinephrine within the
diffuse modulatory systems.
(MAO) degrading enzyme is too active.
Cortex
Rentiofugal Pathway
The retinofugal pathway starts at the retina, synapses onto the LGN
and ends within the striate cortex (visual cortex) of the brain.
Each eye has a visual field in which cross over between the eyes at
the optic chiasm. From the optic chiasm they are segregated all the
way to the LGN and followed by the striate cortex.
Hemi-fields
hemisphere)
(The Where)
Lashleys Theory
Hebbs Theory
Macaque Monkeys
Electrical Stimulation of MTL (Medial Temporal Lobes)
1. Lashley Disproven
Lashley proposed that memories and learning were done all over the
brain and that all cortical areas contribute to memories and learning. His
experiments showed that the size of lesions contributed and therefore must
imply that memory and learning are widespread .
This theory was disproved as engrams show that memory and learning are
more localized to the changes specific structures of the brain. However Lashley
was right that memories are distributed into specific neuronal sections for
processing and storage.
2 . Hebbs Theory Current Theory
Hebbs proposed that the sensory systems, processed and held the engram.
Such as the visual cortex would interpret, process and store visual memories.
Eg: the recognition of faces (shape and color) would be found within the
ventral stream of vision (Area IT)
Cortical areas can be used for processing information and storage of
memories Hebbs Theory
A study was conducted onto two groups of people where one group of people
were experts in motor cars and one groups were experts in birds.
Due to these types of memories being sensory it was hypothesized that visual
processes and memories were done within the same place.
Bird enthusiasts only responded
very well to bird pictures and
being able to tell everything about
the bird, whilst car enthusiasts
only responded very well to car
pictures and could tell everything
about the car.
Summed up
Damaged Hippocampus Degraded perform on maze task and impairment of
declarative memories
Damaged Striatum Degraded on a modified maze task and impairment
of non-declarative memories (habits and procedures).
Modified maze task can include associating a light with food, or without food.
The rats usually use their working + declarative memory to know where the
food is located within the maze. If they have learned procedural/habits to find
the food, then they can find it faster. Damaged to the striatum and modifying
the maze will lead to rats degradation of non-declarative memory and hence
procedural memory (habits/skills/tasks) are impaired.
Case Study
Parkinsons Disease Patients
Amnesiac Patients
`
Diagram showing flow from MTL structures to the pre frontal cortex.
(MCQ)
Instrumental Conditioning
Instrumental conditioning is involved with a behavior which is
associated with a response. For example, a rat that is placed within a box will
eventually bump a lever which releases food. The rat learns through
instrumental conditioning that the behavior of pushing the lever will evoke the
response of the food.
Behavior Associated Response
Learning in Aplysia
Studying Advantages of Aplysia
Non-Associative Mechanism (habituation/sensitization)
Associative Mechanism (Classical Conditioning/Instrumental C)
Studying Advantages of Aplysia
Studies can be taken out on Aplysia which are invertebrates.
Invertebrates such Aplysia are easy to study on due to many advantages their
nervous system which include:
to increase
Synaptic
Cerebellum
The
motor learning.
Parallel fibers and climbing fibers are the pre-synaptic terminals whilst the
Purkinje cell ins the post synaptic terminal.
2.
Climbing fibers
create increased [Na+] and
[Ca++] internally in
the purkinje cell. This
is the core of learning.
3. Parallel fibers release
glutamate which binds to AMPA
receptors and creates the usual 2nd
Messenger cascade.
4. Phosphorylation of
proteins is thought to be the
major step in how synaptic
modification occurs.
5. AMPA receptors are internalized and decrease the EPSP of
glutamate. This where memory is formed.
Learning [Na+]i and [Ca++]i levels intracellular and the
activation of Protein Kinase C (PKC)
Memory
LTD and LTP are the basis of learning and forming declarative memories
in the Hippocampus
Just like we saw in the cerebellum with the parallel fibers and
climbing fibers, it was input specific by the simultaneous cooperation of the two.
We need input specificity by high frequency EPSP to the CA1 cell
within the hippocampus. This will give a strong response or a Long
Term Potentiation (LTP).
LTP can last for days, months, years or even a life time! No wonder
we can remember specific events from our early childhood. As they
created enough high frequency input to form a LTP.
the
to AMPA
Therefore strengthened
pathway! Stronger pathway, more
AMPA
receptors. The linking of neurons. Its creating
fucking declarative facts! And its fucking
awesome! This is your fucking brain at the
molecular fucking level making sure you
fucking remember that fucking
quadratic equation formula in your maths exam. Like umm? Omg wow tehe
Both LTP and LDP can occur through NMDA Receptors (BCM theory)
Both LTP and LDP can be made, dependent on the influx of Ca++.
Symptoms
Positive Symptoms (extravert) : Abnormal thoughts and Behaviors
Delusions
Hallucinations
Disorganized speech (you have no idea what they are talking about)
Very disorganized and very catatonic (abnormal movements)
Negative Symptoms (introvert): Emotionless and non-responsive
Reduced
Non to little speech
Difficulty in initiating a behavioral goal (shaking someones hand)
Memory Impairment.
Schizophrenic patients have enlarged ventricles. A
MRI and CT scan usually shows the reoccurring patterns
of these enlarged ventricles within schizophrenic
patients.
This scan shows identical twins. One with
schizophrenia and the other without. If twins share 100%
identical genes and there is only a 50% chance of one
having schizophrenia where is the other 50%?
Environmental factors must been taken into account
then to set off schizophrenia. These are usually around
pregnancy and development.
Malnutrition
Drug abuse of mother (amphetamine)
Viral infections
Biological Reasoning
Genes and Environment : Inherited through family/malnutrition
Dopamine Hypothesis : Amphetamine and increased Dopamine
Glutamate Hypothesis : PCP and blocking Glutamate NMDA
1. Genes and Environment
Genes: Schizophrenia can be a inherited mental disease in that the
more genes you share with a family line of schizophrenics will
increase your probability of acquiring the debilitating disease.
Environment: schizophrenia can be brought on by environmental
influences such as
o Poor nutrition during maternal care (drug abuse, nutrional
deficits)
o Stress within the environment
o Viral infections during fetal and infant development.
Biochemical Hypothesis : Dopamine and Glutamate
Dopamine Hypothesis : Excessive Dopamine
Amphetamine when used increases the Dopamine levels within the
brain causing euphoria and activating the reward system of
dopamine. As addiction persists, high doses are implemented to fulfill
craving. Overdose on Amphetamine closely relates to
Schizophrenia patients.
Excessive Dopamine levels within the brain are attributed to
Schizophrenia. Psychotic states occur when levels of Dopamine
suddenly rise.
o Too many D2 (Dopamine) receptors are found, thus too much
dopamine excreted.
o Treatment involves blocking D2 receptors using neuroleptics to
lower the levels of Dopamine activity.
Glutamate Hypothesis: Reduced NMDA Glutamate receptor
PCP was previously used as a anesthetic drug but was stopped as
patients post-operative were having hallucinations and hearing voices.
Today PCP is unfortunately a illicit drug used for recreational use
Angel dust or Hog.
PCP blocks NDMA channels and causes very similar symptoms of
Schizophrenia in drug users.
Treatments
Conventional Neuroleptics - Chlorpromazine and Haloperidol act on
D2 within the brain to reduce the amount of Dopamine.
Heavy side effects as the Substantia Nigra affiliated for Dopamine is
down regulated a lot and exhibits Parkinsons Disease
Muscle Rigidity, impaired non-declarative memories, tremors and
difficulty in coordinating movements.
Research: Studies are in increasing the NDMA expression within the brain
together with reducing D2 receptors within the brain.
at
Now we are
looking
the
ventral
horn
where motor neurons
are
to travel along the ventral root to
innervate peripheral muscles.
Lower motor neurons are found
within the spinal cord. These are the neurons
receive the message from the higher neurons
brain. Contraction is exclusively taken out by
lower motor neurons.
held
which
in the
MCQ
MCQ
Alpha
neurons
innervate
muscles
are the
neurons
allow contraction
occur.
and
motor
fibers
who
to
neurons
Golgi Tendon Organs send information about muscle tension. In other words,
make sure you dont rip your muscle off the bone. These Golgi tendon organs
are located in the two poles of the muscle tendon and have 1b Sensory Neurons
innervating them.
1b Sensory Neurons innervate Golgi tendon organs. Another form of
proprioception and part of the reflex arc if the muscle is under too much
tension. Although can be overridden by higher cortical areas.
Overview of Neurons
Alpha Motor Neurons Extrafusal Muscle Fibers
Gamma Motor Neurons Intrafusal Muscle Fibers (Muscle Spindles)
1a Sensory Neurons
Innervate extra and intra muscle fibers
1b Sensory Neurons
Golgi Tendon Organ
Proprioception at Joints
The combination and workings of muscle spindles, Golgi tendon organs and
skin receptors.
Interneurons Excitatory and Inhibitory
Inhibitory Effect
Start
questions
Brain Control of Movement
excitatory actions of
the interneurons excite
alpha motor neurons for
flexors to contract and
remove from painful
stimulus. At the same time,
interneurons cross over to
other side of the body to
inhibit the flexor action on
the other leg. Instead the
extensors are stimulated to
take load while the other
leg is being removed.
More notes..
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