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study of the nervous system
what is neuroscience?
molecular bio, cell bio, physiology, chem, physics, psychology, cognitive science, comp sci, and math.
What other sciences are in neuroscience?
neuron
nerve cell
in almost all animals
most important
can’t be made easily
however connections can change
many subtypes
nucleus
DNA is stored
found in cell body/soma
contains cytosol
separated by neuronal membrane
dendrite
brings input to the cell
comes from greek word for tree like
can have many branches
like an antenna
size and shape of spines = ability to receive input there
can have multiple
axon
typically have one only
serves as wire to transmit output from a neuron
uniform thickness and can be several feet long
no organelles inside it
can be covered in myelin to help send signals
begin at soma
at a part of the axon called the axon hillock
end at slightly larger sections called axon terminals
structure is made of microtubules
myelin
fatty substance from the glial cells
insulates axons
like insulation on a wire
looks white even without stains
fatty
Nodes of Ranvier
small gaps in the Myelin coat of an axon that allow the axon to take in fluids
Axon Hillock
part of the axon that’s connected to the soma
Axon terminal
slightly wider end of axon
where the neuron will release the neurotransmitter
also through electric impulse
usually to another neuron’s dendrite spine
Synapse
point of communication between neurons
not connected
synaptic cleft
gap between two neurons at a synapse
presynaptic neuron
the transmitting neuron
the axon terminal is usually filled with spherical packets (vesicles)
neurotransmitters
postsynaptic neuron
the receiving neuron
neurotransmitters
produced in soma
sent down axon to terminal
bind to receptors that receive the the signal on postsynaptic neuron
packaged into vesicles
morphollogy
shape of a neuron
dendritic arbor
size and shape of the branching dendrites
related to the region of the body that the neuron receives from and how it can send signals to other neurons
examples of how structure = important to function
motor neurons
soma at one end with a small set of dendrites and a big axon to connect to muscle
sensory neurons
some have dendrites at both ends connected by a long axon with he cell body somewhere in the middle
interneurons
often quite small without long axons or dendrites
interneuron
work to connect other neurons within the nervous system
grey matter and white matter
what are the two types of tissue in the nervous system?
grey matter
made of cell bodies and dendritic arbors of neurons
mostly on the outside of the brain
inside for spinal cord
white matter
made of myelinated axons of neurons
tucked inside brain
outside on spinal chord
Glia/Glial cells
non neuronal cells found in the nervous system
variety including
strocytes,
oligodendrocytes,
Schwann cells
microglia
produced throughout the life of an organism
once thought to be passive
Schwann Cells
form the myelin sheath around axons in the PERIPHERAL nervous system
Oligodendrocytes
form the myelin sheath around axons in the CENTRAL nervous system
Astrocytes
most common
star-like appearance
regulate chemical makeup of extracellular fluid between cells in the nervous system
remove excess signaling molecules and maintain proper balance of ions
also react to tissue damage
send out long extensions that wrap around blood vessels in brain to create blood brain barrier
once thought to be passive
can alter signals that are sent and received
helps keep neurons nourished
blood brain barrier
keeps stuff in the blood out of the brain
keeps the brain from getting infections from damaged neurons
makes it harder for nutrients to get into the brain
also hard to get drugs in there to help stop disease
Microglia
smaller than other glial cells
immune cells of the brain
clear away pathogens and damaged/dead neurons
it does so by eating them
similar to macrophages in our normal immune system
hyperactive ones can actually end up damaging the brain
can play a role in neurodegenerative diseases eg. Alzheimer’s
Central nervous system
two parts encased in bone
brain
spinal cord
nervous system doesn’t have contact with bones
three layers of meninges surround the system to protect it
dura mater, arachnoid membrane, and pia mater
What are the three layers of meninges protecting the central nervous system called?
dura mater
latin for tough mother
outer most layer
thick and leathery
spall space between it and skull
filled with fats to absorb shock
called epidural space
useful for injections
arachnoid membrane
long stringy components that look like spider webs.
usually very little subdural space (space between arachnoid and dura mater)
brain trauma can put blood there
subarachnoid space
space below arachnoid membrane
filled with cerebrospinal fluid
cushions/protects brain allowing it to float
allows blood vessels room to go to brain
allows it to get oxygen and nutrients
pia mater
latin for gentle mother
very thin
fits Brian very closely
keeps cerebrospinal fluid out of brain but allowed blood to pass through
Peripheral Nervous system
consists of nerves/axons and some ganglia that are apart from the central nervous syste
basically the relay between central nervous system and the outside world
more easily damaged (bc no bones) and reparable
no BBB means easier to get infected
has different sections
Ganglia
clusters of cell bodies
Somatic and Autonomic
What are some parts of the peripheral nervous system?
Somatic Nervous system
composed of all axons leaving/entering spinal cord that brings info to and from the tissues of the body
includes the axons above the spinal chord that brings motor commands or sensory input of the head and neck
voluntary control
Autonomic nervous system
involuntary responses
regulates functions of internal organs, smooth muscle (heart) and glands
name comes from greek word Autonomia
two divisions
Sympathetic and parasympathetic
What are the two divisions of the automatic nervous system?
Sympathetic nervous system
fight or flight
comes from adrenal glands from stress
circuits of this division start with a neuron in CNS (usually in thoracic or lumbar parts of SC)
this neuron synapses to a neuron on the sympathetic chain
axon from this new neuron goes to the desired organ
chain design = good for general message to general audience
MEANT FOR SHORT TERM ONLY
long term use = chronic stress and damage
sympathetic chain
specialized chain of ganglia next to the spine
heart (increase BP), lungs (increase breath rate), digestive system (Bile production) secretory glands (sweat, tear, and saliva production)
What are the targets of the sympathetic nervous system?
Parasympathetic nervous system
rest and digest
connected to Brain stem and Sacral Spinal chord
ganglia involved are scattered everywhere
usually close to the organ that the second neuron in the sequence is targetting
this organization isn’t good for speedy general messages
its good for super specialized instruction
the role of this is balance
things that activate the parasympathetic nervous system
digestion
cell growth/devision
immune responses
energy storage
homeostasis
same as sympathetic but opposite affects.
What are the targets of the parasympathetic nervous system?
membrane potential
way of describing the electrical charge a cell has in comparison to the charge outside (measured in millivolts mV)
resting and action
what are the two main potentials?
cytosol, extracellular fluid and neuronal membrane (separates the two)
What are the three things that dictate the potentials?
Resting membrane potential
electric charge inside the neuron compared to outside when neuron is at rest
similar to the eq potential for K+ because of the leak channels
usually negative
about -60mV or -80mV
neuronal membrane
allows the electric charge of inside of the cell to be different than outside.
wall preventing/inhibiting changes in [ion]
goes through channels
phospholipid bilayer
passive transport
natural force (no req energy)
done by [] and electric potential.
Active transport
requires energy
pumps
How do ions cross the membrane
ion channel
proteins that form specialized openings for ions
usually specific for ions
eg sodium channel
can also be gated
must be triggered open
some are triggered by changes in environment
voltage-gated
If the channel opens when the membrane potential is at a particular voltage it is?
this type also usually opens when voltage changes from rest
Ligand gated
open when a particular molecule binds to a specific location
this changes the conformation and opens the channel
intensity of flow comes from natural forces
NA/K pump
crucial in neurons for resting potential.
breaks down ATP and changes its conformation
takes two K (from outside) in phos state and 3 Na in dephos state
exchanges Na for K.
increases [] gradient
always in background
helps restore to normal concentration gradient after the falling phase
Potassium leak channels
open and ungated
allow positive potassium to just leave
causes negative rest potential
Electrical Driving Force
when the electric potential outside the cell becomes strong enough so that the K+ are repelled and sent back into the cell through the leak channels, what driving force is exhibited?
size of this force is proportional to the electrical difference inside and outside the cell
Chemical driving force
the result of the [] gradient. It causes the initial diffusion. size of the force is proportional to the []
when Chem and Electric Driving force are equal
When is the cell at eq?
eq potential
the membrane potential at which a particular ion reaches eq. (each ion will have a different one)
Nernst Equation
gives the value of eq potential for an ion.
takes in the following factors:
temp of cell
ratio of external internal [] in ion
Goldman Equation
Starts from Nernst Equation but factors in the permeability for multiple ions (like Na, K, and Cl)
Active membrane potential
the electric potential across the membrane when the cell is active and firing
brief drastic change usually only for a few milliseconds
AKA spikes, nerve impulses or APs
rising phase, peak/overshoot, falling phase
What are the phases of Action potential?
rising phase
first phase of the action potential.
membrane experiences depolarization
depolarization
when the membrane potential becomes more and more positive
peak/overshoot
when the charge inside the cell becomes more positive than the outside of the cell
usually goes up to +30mV or +40 mV
Falling phase
final phase before reset
becomes more negative due to loss of + ions
this is known as repolarization (returning to polarized)
or hyper polarization (becoming more polarized)
However it continues and the membrane becomes extra negative stopping at around -80mV
this is called undershoot/afterhyperpolarization
light or darkness in the retina
inner ear neurons respond to sound waves
neurons in skin respond to heat, cold, pressure, pain
Examples of triggers for action potential in neurons
raise the charge of the membrane potential to smt more positive, usually between -65mV and -50mV
What do the stimuli have in common?
All or none principle
the idea of either firing or not
cell either reaches threshold and fires or doesn’t
reaches the requirements to open the sodium gates
this allows for a rush of Na because of the high [] gradient and high electrical driving force
this rapidly depolarizes the cell
(those channels get blocked again once the cell reaches it’s peak phase)
Why is this threshold so important?
Absolute refractory period
the one millisecond that the sodium gates are inactivated after an action potential
another action potential can’t happen at this time
is also the reason that signals only go one way
Voltage gated K gates
open when the potential = approx 0mV
slow to open and close
starts opening at peak
use the large [] gradient of k to push it out of the cell
also electric potential is present
causes hyper polarization
also causes afterhyperpolarization bc it is slow to close
effluxes
flows out of the cell
Relative refractory period
the time period where more the potential is more negative due to the afterhyperpolarization
more stimulus needed to reach threshold at this point
propagates
to be carried down the axon
when sodium enters the cell, it dissuades through the axon which triggers the next set of channels which leads to a cycle of triggering throughout the axon
Why does’t the signal degrade or decrease over the length of the axon?
by insulating the axon. However, the signal also degrades a little because it can only be regenerated at each Node of Ranvier.
How does the Myelin sheath speed up action potential?
Saltatory Conduction
conduction down a myelinated neuron
comes from the word saltare meaning jump
bc message jumps from node to node
synaptic transmission
the process in which two neruons communicate
presynaptic cell axon terminal
contains mitochondria to help produce ATP to power transmission
the microtubule of the axon cease at the terminals
electrical and chemical
What are the two main types of synapses?
electrical synapse
the two communicating cells are so close that a single set of channels (gap junctions) connect the membranes
because of this, the positive ions of the Action Potential go straight into the next cell
super fast but no changes
changing the signal is how the Brain encodes info
therefore this synapse is a bit limiting
Chemical Synapse
much more complex of the two synapses
the two cells have two vastly more complicated jobs
Chemical synapse: presynaptic cell
has to translate electric signal to chem signal
axon terminal
crucial voltage gates = calcium
calcium floods in
vesicle
once vesicle with transmitter reaches axon terminal it docks facing the synaptic cleft (active zone) bc of SNARE proteins
this is done before the action potential arrives for quick transmission
Then exocytosis happens
SNARE proteins
special proteins that are membrane bound ad forma. complex that locks vesicles into place
Exocytosis
in fluxing Ca binds to a SNARE protein called synaptotagmin.
this one changes the SNARE complex and brings the vesicle outward so the two membranes can fuse together
creates a pore
allows neurotransmitter to diffuse across synaptic cleft towards the
ionotropic/ligand receptors
work very quickly to change the postsynaptic membrane potential through neurotransmitters
uses endocytosis and stuff
use ion channels
Metabotropic receptors
AKA GPCR
much slower and complex responses
activated in steps
binding of neurotransmitter
activates G proteins
although it may seem similar to the other one, the main difference is that it can activate many G proteins leading to a wider effect
some do more than just activating channel
they can make use of proteins “downstream” of the G protein and alter the cells metabolism
effector
When the G protein is activated, it splits apart into subunits which each go on to activate its own set of signal/ _________ proteins
effector proteins
many different kinds
for example: in some cells, G proteins bind to a special ligand channel. These are special because the gate is towards the cytosol and it’s keyed to only the G protein. In this case the ion channel IS the _________
also ion channels that are activated by G subunits
one pathway involves activation of PKC (Protein kinase C
responsible for many important molecules by phosphorylating them
The G protein binds to the effector protein phospholipase C (PLC)
then splits into two molecules
inositol-1,4,5-triphosphate (IP3)
diacylglycerol (DAG)
this is the branching point bv each molecule acts as a second messenger
IP binds to some ligand gated calcium channels in the ER,
allows internal Ca into the cytosol which binds to signal proteins which have effects
DAG stays on the membrane and activates PKC which phosphorylates a lot of target proteins
== signal cascades
How do metaprobic receptors change metabolism?
phosphorylating
to add a phosphate too
second messenger
when the molecules is produced by the effector protein and diffuses away in the cytosol to impact other parts of the cell it is a _________.
signal cascades
take longer than regular inotropic paths but has a stronger signal
Prozac and Zoloft
Which drugs inhibit reuptake transporter found in synapses that release serotonin.
AKA Selective reuptake inhibitors (SSRIs)
they allow serotonin to have more time to get across the cleft
agonist, or antagonist
What are the two usual ways that drugs impact receptors?
receptor agonist
drug type that helps enhance the effect of the transmitter
usually mimic the action of the endogenous neurotransmitter the receptor binds
competitive agonists compete against the endogenous NT
must be much more [] than the endogenous NT
noncompetetive agonists make the system more efficient and don’t compete
partial agonists compete for the same spot but don’t have as much of an effect
drugs that increase NT synthesis