Physiology Lab #2 Flashcards
CNS vs PNS
CNS - Brain + Spinal Cord
PNS - After nerves/cranial nerves exit (exit out of brain/spinal cord)
Split of PNS
Splits inot the somatic and autonomic
Somatic - Sensory and msucles
Autonomic - Includes sympathetic + parasypathetic (Heart and sweat gland muscles)
Spinal Cord (Sagital view)
Can see the vertabral bodies + can see the split into the cranial/Thoracs/Lmbar nerves
Spinal cord ends at L1/L2
L5 ends at T12 thoracic vertabre
C7 or T12 = spinal level (not exiting vertabral body)
Whats surrounds the spinal cord
Spinal cord is surrounded by mengies (Dura + Archnoid + Piamoter)
- Drua = tough + where the spinal cord exits
Ventral roots in Spinal Cord
Ventral roots = come out of Ventral element
- Vental element (very thin) - often torn in lab or in autopsy (very hard to sampoke venral roots)
Dorsal Root Ganglia
Dorsal root ganglia = sits in intervertibral space
- Sits in the foraman between vertabretes - a little away from the spinal cord NOT right on top
Dorsal root = projects through the dorsal horn and synapse (projects through synapse with snsory or motor nuerons)
Grey matter, White matter, Sulci, Gyri
Superficial layer = see grey matter
gyri - high points - outpuchings
Suci - valleys - invaginatiions
Sulci/gyri = differentiates us with mice (mice have smooth brain)
Lisy ensepholphosy
Disease where the brain is smooth (lethal)
Dorsal root nerves
Dorsal root = sensory nerves –> merges with motor nuerons in the ventral roots
Motor nuerons = in ventral roots
Why have different views of the brain
Different views = show you different things
Example - cornal = see deep matter structures (Ex. see basal ganglia)
***Applies to reading scans - need to pay attention to the view of the scan
Reading MRI scans based on angle
Coronal section - Looking at person facing foward
- see pons
Sagital section - NOW pons looks dfferent compared to in coronal section
Axial - Looking at feet foward if you were to be by their feet (right side of image is the left side of the persons body)
Answering dfferent question depening on view
A - Ventral view - can see brainstem
B - BIG line in middle = central sulcus (seperates the two hemispheres)
- Can also see sinus
C - se the cerebelum
Brainstem + cranial nerves
The cranial nerves exit from the brainstem
Sinuses in brain
Carry venous blood
Sinuses = within the memgies
Subarchnoid veins = where the venous pools sit
Why remove 50 mL of CSF
If you have build up of fluid in the brain –> removing 50 mL provides tension relief
- 50 mL = high volume tap
Vs. 20 mL is used fro diagnostics (sample bacetria + cell count)
- If take 20 mL the fluid is replaced in one hour
Cerebrospinal Fluid (CSF)
Functions:
1. Cushions the brain and spinal cord
2. Supplies nurtiesnts to the brain
3. removes wate products that result from brain metabolsim
**Adults have 150 mL of CSF
**Up to 50 L can be draine dBUT typically drain 20 mL
**Normal raite of CSF production = 20mL/hou r
**Entir CSF is replaced every 7.5 hours
CSF replacement
CSF = associated with arterial and venous
Arterial. = push CSF to CSF space
Venous = Absorb CSF
***Get constant turnover of blood and CSF
What is found in CSF
CSF = contains biomarkers for nuerological disease
Glymfatic system
Gets waste away form the brain
- Lymphatic system of the brain
Sampleing CSF
Use lumbar puncture for sampling CSF
sampling CSF = important in diagnostics
Have an emerging role in development of biomarkers in CSF for disease and therputics
- Ex. Infection or mengitus or multiple sclerosis –> have biomarers of what is happening in the brain BUT can’t take out the brain for biopsy = use CSF
Does Lumbar tap affect spinal cord?
When put in needle for lumbar tap - the needle goes to C4 or L5 vertabret (below the spinal cord = won’t injure the spinal cord)
- There are nerve roots = could cause pain
CSF = windo into what is going on in brain or spinal cord
Grey Vs. White matter
Grey = where neurons sit
- Grey = split into motor nuerons and intervenous nuerons
White = Myelin (primarily form oligiodendricytes)
- has tracks of nuerons
Grey matter = surounded by white matter
B12 deficneicey
Involoves dorsal tracals and cortecus spinal tracks –> clincally develops pathology related to these abnormaloties
Imaging of White and grey matter
Can see diference in imaging - grey and white matter are different radiologicaly
Image -
1. White layer around top = fat layer within the skull
2. can see ventrical (has CSF - black part is CSF)
3. Thin grey around the gryi = Dura layer suroudning the brain
Spinal cord englargments
Spinal cord = has enlargments
Englargments = in cervical and lumbar areas
- Have englargments because these areas have nerves for arms = have many tracks/nuerons going to arms because hvae lots of motor nuerons and sensory axons in arms (cervical area) = have englargments (Same idea for lumbar areas)
Compared to thoracis - thin because just affecting intercaustal muscles = fewer muscles = less nerves
Sagital Section of spinal cord
Image 1
White = CSF
Small bone like on right = spinous process of vertabrete
Big bone on left = Vertabrete
Image 2 - CSF = dark
Axial Section of spinal cord
White = spinal cord
Left side = right side of pateint
Top = Ventral
Bottom = Dorsal
Lumbar part of spine
Can see the spinal cord end and nerves exit through intervertebral foraman
At end = have a series of nerves come out of spinal cord = caudual quina
Cadua Quina
Series of nerves coming out of spinal cord
Ventral root
Thing going towards the left
Spinal Reflex
Have the dorsal root ganglia –> then goes to dorsal neuron –> synapsse to internueron –> activates quadriceps muscles and inhibits hamstrng muscles = get relex
- hamstring = angtagonist muscle
***Considered afferent response
Major Pathway from CNS to PNS
- Motor pathways
- Sensory pathways
homoculous
Shows contromutions (amount of cortext) that inerculing relation region
See leg = medial aspect of hemisphere
Hand = large represnetation + face/tongue is large –> have a lot of cortext for these areas = allows fine motor movement
Legs = less fine movement = less neurons = smaller on humunculous
Motor pathways from CNS to PNS
From cortex to spinal motor neurons –> move muscles
- Have lateral corticospinal tract –> goes to synaspse on moto nueros –> goes to skelatal muscles
LOOK AT IMAGE
Sensory Pathways
- Dorsal Column system
- Spinothalamic tract
Dorsal Column system
Function
1. Sense fine touch
2. Periopersepction (know where you are in space)
Ex. B12 defeincey - can’t talk because you don’t know where the leg is n soace because B12 affects dorsal sensory oathway (IF pateints look at legs then they can wlak)
Spinothalamic tract
Function - pain and temperature
Cells types in CNS and PNS
CNS:
1. Nuerons - have many types –> different based on region
2. Astrcytes - have many subtypes (push to understand the subtypes)
3. Oligiodendrycytes - have many subtypes (push to understand the subtypes)
4. Microglia - have many subtypes (push to understand the subtypes)
5. Endothelial cells
PNS:
1. Schwann cells - Mylenate cells of PNS
2. Muscle
Anatomy of a neuron
Parts
1. Dnedrites (branches)
2. Cell Body (aka Soma)
3. Nuceus - contains genetic infomration
4. Axon
5. Mylin sheat (image = yellow part)
6. Axon terminal
Dendrite
Branched part of the nerve
Function - receives input from synapses (receives signal from other nuerons)
Cell body
Aka Soma
- Can be bigger depending on the subtype (Image = can see nuclei next to bigger soma - tehse smaller nuclei are the astrocytes and microglia - shows how big soma can be)
Function - contains the nucues + other organelles (Mitocondria + ER etc)
- Buissness end of cell (doing transcription/tranlsation) –> proteins made would then go to dendrites and axons
Axon
Conducts electrical impuses along nueronal cell
Can be very long (up to one meter in humans) (ex. cell body can be in spinal cord and axon goes to feet)
Myeilin sheeth
Insulates the axon to protect the nueron and speed up the transmission of electrical impulses
- Leafing wrapped around the axon
CNS = oligiodendrites surround axon
PNS = Schwann cells surround azon
Axon terminal
Transimitts electrical and chemical signals to other nuerons and effector cells
Nueronal Diversity
There is a lot of nuronal diveristy
Types of nuerons:
1. Unipolar
2. Bipolar
3. Pseudounipolar
4. Multipolar
Purkinie cell
Very distict cell type
Good exmaple of a dedritic tree
Axons = single projections into cerebelum
Shape of dendrites
NOT single branch - is many branches with buds
Image - can see dendritic spines –> area whete dendrute synapse is formed
- Long term potential of dendrites - how we form our memebories –> because dendrite spine changes
On dendrites = have receiptors that sit on dendrites (receive signals)
Denderite vs. cell body
Past vs. present thoughts about axons
Past - thought that nuerons synthesize proteins in soma and the proteins travel meters along axon t diffreent places
Now - know proteins are made in the axon themselves
Axon regeneration
If cut an axon it will heal 1 mm per day –> means that if you have an injury you can calcute how long it will taje to reinervate muscle
Issue - after 18 months miscle loses regernation capacity if the axon cannot heal in that time = then doctors might do surgery
Axon Hillock
Transistion between the soma and axons
Function - where the electrcal signals are summed –> get Action potential
- Intiator of action potential
Structural components of Axons
- Microtubules
- Neuroflilaments
Microtubules
Long polymers of tubulin dimers
- Larger
Function - Traffics things up/down axon (Things move on microtubules up/down axon)
- Ex. Move mitocondria
Nuerofilament
Have 3 types:
1. Light
2. Medium
3. Heavy
Woodwork of axon (Building blocks of axon)
Used to measure in CSF and blood – if you cut a nerve then the nuerofilaments are broekn = can see nuerofilaments in CSF = use this as a biomarker for disease
- Ex. ALS – see changes in Nuerfilaments over time (lower neurofilaments = slowing of disease progression)
Axoplasm
Cytoplasm of Axon
Axon Transport
- Retrograde transport - movement of things from distal to soma
- Slow (200 mm/day) and backward
- Uses Dynein (moves endosomes + mittocondira + neutrophic signals + toxins + Viruses)
- Anterograde transport - movement of things from soma to distal
- Foward moving
- Has slow transort or fast trasnprt (Fast = 400 mm/day ; slow = 0.5-3 mm/day)
- Fast Uses Kineisin (carries proteins or organelles or vesicles)
- Slow = uses kinesis to move tubulin + Actin + NF and SOD1 “Go pause Go”
BOTH = occur on microtubules
Proteins used
Nodes of Ravier
Gaps in mylin sheath
Exposed regions of axons –> allows for rapid transmission down axon
Have Na chanels in node – allows the action potnetial to be transmitted down the axon
Important characterstic of neurons
Neurons are excitable –> are able to transmit electical signals down axon –> then get the data in the dendrite –> then do things in the soma
Action Potential Pumps
- Na/K pump - let Na out of cell and K into cell –> allows cell to be at resting potential (~ -70 mv)
- K pump - K goes out of cell
- Na chanel - Na into Cell
At rest - K and Na pumps are cloced ; Na/K are pen and Na is going out of cell and K goes into cell
Generating action potential
Have something that stimulates the neuron – Na chanels open in resonse –> Na goes into the celll –> Action potnetial travels down –> As AP travels down more Na chanels open = get propogation of AP
NOW - the upstream Na chanels close (only open for a short time) –> K chanels open –> membrane potential is restored to -70 mv
Chart of membrane potential volatge:
1. Na chanels open - Na enters the cell = Na goes in = increase volatge in cell (memebrane potential becomes less negative)
2. As Na open K also opens = K leaves cell
3. Na chanels close - no more Na in cell but K is still open
4. Na still closed
5. K chanels close, Na chanels reset
6. Extra K diffuses away
Action potential on mylinated vs. Unmylinated
No mylin = need action potential on entire membrane (all the way down)
Mylein = only need Action potential at exposed regions
- Creates Saltator conductions –> Action Potential (depolorization) only needs to occur in gaes = jump from gap to gap = faster conduction down nerve
Nerve conduction Study
Median speed 49 meters/second
IF take away myline (ex. in gycanber syndrome) – Now speed is 21 meters/s –> becase the mylin is gone = no saltador conduction = slow response
Nuerotrasmitters types
- Classical (Ex. Acytlchorline used at nueromuscular junction)
- Amino Acid (Ex. Glutamate - makes up most of the nuerotransmitters in the brain; GABA)
- Peptide (Ex. Opiate)
- Gaseous (Ex. Nitric Oxide)
Stiff person syndrome
Person us unable to produce GABA = cells are hyperexcitable = get stiff
- Have Antibodies against things that make GABA
Why can we differentiate between different forms of tactile touch
Cells receive signal (General EPSB) –> Na chanels open in dendrite –> Cell becomes depolarized (less negative) –> Get Excitatory EPSB –> Activates nueron
AND
Cells receive signal –> activate in motor nueron –> Cl goes into the cell –> cell becomes hypopolarized –> Get INhibitory IBSP –> Silences nueron
CELL - summs the EPSB and the IPSB - Cells gets excitatory and inhibitory inputs at the same times and sums them up anotomically and temperaly
Excitatory and inhibitory buerotransmitters
Glu - excitatory nuerotransmitter – gets released from presynatptirc membranes –> binds at the post synaptic memebrane —> Na chanels open –> Get Action potential
Gly and GABA –> inhibitory neurotranmitters –> Realased to post synatic memebrane –> Opens Cl chanels –> get hypopolarization
Integration
The algebraic summation of inhibitory and excitatory synaptic potentials
Occurs in the neuropil (Usually at the initial segments of cell)
How can you get an action potential when have multiple things firing using Integration
Scenerior 1 - Stimulus is fired from an excitatory input BUT you don’t reach the Action potnetial (Very little excitation input that is not enough for an Action potential) –> No AP
Scenrior 2 - IF a Synpase fires twice = have a temperal summation = get Action Potential
Scenerio 3 - IF 2 excitatory synapses fire together –> Get Action potential (Spatial integration)
- Have input from multiple synapses
Scenrio 4 - IF you have an inhibtory synapse –> get deflation BUT you also have excitatory fireing –> Summation of inhibitory and excitatory is not enough for Action potential –> No AP
- It is possible that this could sum to get AP if excitatory is higher
Charactristic of Action potnetial
Action potentials are all or nothing
Oligio dendrites vs. Schwann cells
1 Oligiodendrite envelopes senveral axons AND oligiodentrites only have one layer of mylin around axon
- Oligo = in CNS
Schwann = Can have multiple layers
- Schwann = in PNS
Astrocytes
Function - supporting cells in brain
1. Envelope the synapse
2. Interact with vasculator
3. Instruct epithelial cells of brain capilaries to defenestrate
4. Astrocytes = active in the synape + modulation + Maitnance of metabolsim in CNS
More Atrocytes in cell compared to nuerons
Issues with astrocytes = affects how the synapse behave
What makes the Blood Brain barrier
The tight junctions between endothelial cells make up the BBB
Tripartide
Presynapse + Post synapse + Astrocyte
Astrocyes = absorbs extra neurotransmitters + release nuerotransmitters
Microglia
Function:
1. Important for development - Involved in synaptic pruning (prune synaotic spines away)
2. Regulates nueronal circuts (Ex. release ATP)
3. CNS maintance
4. Phagocytoces
5. Releases Growth Factors
Affects disease - over activation can lead to cell detah (target in neurodegernative diseases)
Schwann cells
1 Axon = has 1 schwann cell
Schwann cells = forms lameals –> More Lamals = faster conductions
Disease example - ECM benget Syndrome –> Have stripping of mylin –> conduction velacity slows –> have weak
Staining peripheral nerves
Staining = done in practice –> cut erves and can see mylination (can see thickness of mylin)
Images:
Left - Axons are stained black
Right - Axoplasm is white ; Can see mylinated axons (Mylin is black)
Synaptic Transmission
Packaging Neurotransmitters = Takes a lot of energy
Nuerotransmitters = encased in vesicles –> Vesicles are snet to the synapse –> When the cell is depolaorzied Ca goes to the synaspse –> Get fusion of vesicles with memebrane –> Release nuerotransmitters to the cleft –> Neurotrasmitters go to the receptors on post synaptic surface
Overall - Load vesicles with NT - Vsciles fuse with memenbrane - Release contents of the vesicles
Synaptic proteins
Synaptic transmission = complex (Uses many proteins)
Uses more than 1000 proteins in presynaptic nerve terminal and over 100 proteins function in exocytosis
Choligernic synapse
Image (Left) - shows steps
Image (right) - vesicles with Achetylcholine fise with presynatptic –> contents go to synaptic cleft
Acytlcholine = important in CNS (implicated in alzheimers)
Nueromuscular Junction
Acytlcholine is rekeased from motor nuerons –> Acytlcholine binds to the Acytlcholine receptors –> Na chanels open –> Get muscular depolarization –> AP opens the T-Tubulues –> S (Has Ca) opens –> Ca is released –> As Ca binds to troponin complex there is a conformation shift = other binding sites are exposed = Actin is able to bind to myosin = get muscle contraction
Types of axons
There are different Axon types for different modalities
Example - Different types for priopoception + touch + Mechanical/thermal + Pain
Types of receptors
Have many different forms
Example - can have a free nerve ending or tarctile areas around hair or ruffini ending or corpsicle –> different endings transmit different sensory responses
Refractory neurons
Sensory neurons can become refractory (become desensitived)
Example - don’t feel clothes because nuerons bcome desensituzed
Models for nervous system
- Mice (Ex. have ALS model - ind limbs are lagging)
- C. Elegans - quick and easy (can model different diseases)
- Drosphila - Morpholgy can be derived + easy mutated + fast cycle
- Zebrafish - Can see things developmentally
- Cell culture - Ex. hiPSC
- Yeast - East to grow and screen
Things to use for biomarkers
There is a BIG effort to find biomarkers
Things to use:
1. Blood
2. Spinal cord and brain tissue biopsy (hard to do + can only do few times)
3. Urine
4. Skin (Punch Biopsy) - Can evaluate nerve fibers or DP43 protein (What is seen i brain can be reflected in skin)
5. Muscle
6. Electrophysiology - use for diagnosis
7. PET imaging - Can see CNS (Use for cancer + Alzheimers)
8. CSF
Issue with using blood for biomarkers
Can’t always see things - espcially because of Blood Brain Barrier
Issue with Biomarkers
Lack reproducibilty - people get different results
Recent Rise in gene discovery
Example ALS
1994 - found 1 ALS gene –> Gene discovery was flat until 2010 –> After have rapid discovery of genes related to ALS
Recent discovery of genes - can use this inofrmation to make models (Can introduce muttaions to fly or mouse and get model of disease)
Discovery of iPSCs
Discivered by Takahasha
How - Took skin from mice first then humans
- Took skin –> take the fibroblasts out –> add in 4 diferent factors (KLF4, SOX2, c-MYc, Oct3/4) –> get stem cells –> can diferentae cells ro se in the lab OR can reintroduce them to people for treatment
Issue with iPSCs = expsnsive + human iPSCs are slower to grow than mice
Versitity of iPSCs
Versitle human iPSC platforms allow for study of cell types involoved in nuerological diseases
IPSCs can be used:
1. Record electrophysiology
2. Can mix will cells (Co- culture ALS nueronal cells with normal astrocytes)
3. Induce cell stress
4. Drug screen
5. Study disease
Oppertunity to idetify mechanism of disease
use iPSCs from ASL pateins
Can Asses for ALS pathology + functional assays (Electrophysioogy) + Vulnerability to cell stress + Modeling non cell autonomous contrbutions to motor cell + drug screening
Diseases of nervous system
Parkinsons + Alzhemiers + Huntingtons + ALS + epilespy + Ataxia + Multiple sclerosis + Peripheral nueropathy + Neoplasia + Stroke + Infection disease + Prior disease
