Physiology Lab #2

Question 1

CNS vs PNS

Answer 1

CNS - Brain + Spinal Cord

PNS - After nerves/cranial nerves exit (exit out of brain/spinal cord)

Question 2

Split of PNS

Answer 2

Splits inot the somatic and autonomic

Somatic - Sensory and msucles

Autonomic - Includes sympathetic + parasypathetic (Heart and sweat gland muscles)

Question 3

Spinal Cord (Sagital view)

Answer 3

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)

Question 4

Whats surrounds the spinal cord

Answer 4

Spinal cord is surrounded by mengies (Dura + Archnoid + Piamoter)
- Drua = tough + where the spinal cord exits

Question 5

Ventral roots in Spinal Cord

Answer 5

Ventral roots = come out of Ventral element
- Vental element (very thin) - often torn in lab or in autopsy (very hard to sampoke venral roots)

Question 6

Dorsal Root Ganglia

Answer 6

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)

Question 7

Grey matter, White matter, Sulci, Gyri

Answer 7

Superficial layer = see grey matter

gyri - high points - outpuchings

Suci - valleys - invaginatiions

Sulci/gyri = differentiates us with mice (mice have smooth brain)

Question 8

Lisy ensepholphosy

Answer 8

Disease where the brain is smooth (lethal)

Question 9

Dorsal root nerves

Answer 9

Dorsal root = sensory nerves –> merges with motor nuerons in the ventral roots

Motor nuerons = in ventral roots

Question 10

Why have different views of the brain

Answer 10

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

Question 11

Reading MRI scans based on angle

Answer 11

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

Question 12

Answer 12

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

Question 13

Brainstem + cranial nerves

Answer 13

The cranial nerves exit from the brainstem

Question 14

Sinuses in brain

Answer 14

Carry venous blood

Sinuses = within the memgies

Subarchnoid veins = where the venous pools sit

Question 15

Why remove 50 mL of CSF

Answer 15

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

Question 16

Cerebrospinal Fluid (CSF)

Answer 16

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

Question 17

CSF replacement

Answer 17

CSF = associated with arterial and venous

Arterial. = push CSF to CSF space
Venous = Absorb CSF

***Get constant turnover of blood and CSF

Question 18

What is found in CSF

Answer 18

CSF = contains biomarkers for nuerological disease

Question 19

Glymfatic system

Answer 19

Gets waste away form the brain
- Lymphatic system of the brain

Question 20

Sampleing CSF

Answer 20

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

Question 21

Does Lumbar tap affect spinal cord?

Answer 21

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

Question 22

Grey Vs. White matter

Answer 22

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

Question 23

B12 deficneicey

Answer 23

Involoves dorsal tracals and cortecus spinal tracks –> clincally develops pathology related to these abnormaloties

Question 24

Imaging of White and grey matter

Answer 24

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

Question 25

Spinal cord englargments

Answer 25

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

Question 26

Sagital Section of spinal cord

Answer 26

Image 1 White = CSF Small bone like on right = spinous process of vertabrete Big bone on left = Vertabrete Image 2 - CSF = dark

Question 27

Axial Section of spinal cord

Answer 27

White = spinal cord Left side = right side of pateint Top = Ventral Bottom = Dorsal

Question 28

Lumbar part of spine

Answer 28

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

Question 29

Cadua Quina

Answer 29

Series of nerves coming out of spinal cord

Question 30

Ventral root

Answer 30

Thing going towards the left

Question 31

Spinal Reflex

Answer 31

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

Question 32

Major Pathway from CNS to PNS

Answer 32

1. Motor pathways 2. Sensory pathways

Question 33

homoculous

Answer 33

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

Question 34

Motor pathways from CNS to PNS

Answer 34

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

Question 35

Sensory Pathways

Answer 35

1. Dorsal Column system 2. Spinothalamic tract

Question 36

Dorsal Column system

Answer 36

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)

Question 37

Spinothalamic tract

Answer 37

Function - pain and temperature

Question 38

Cells types in CNS and PNS

Answer 38

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

Question 39

Anatomy of a neuron

Answer 39

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

Question 40

Dendrite

Answer 40

Branched part of the nerve Function - receives input from synapses (receives signal from other nuerons)

Question 41

Cell body

Answer 41

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

Question 42

Axon

Answer 42

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)

Question 43

Myeilin sheeth

Answer 43

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

Question 44

Axon terminal

Answer 44

Transimitts electrical and chemical signals to other nuerons and effector cells

Question 45

Nueronal Diversity

Answer 45

There is a lot of nuronal diveristy Types of nuerons: 1. Unipolar 2. Bipolar 3. Pseudounipolar 4. Multipolar

Question 46

Purkinie cell

Answer 46

Very distict cell type Good exmaple of a dedritic tree Axons = single projections into cerebelum

Question 47

Shape of dendrites

Answer 47

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)

Question 48

Denderite vs. cell body

Answer 48

Question 49

Past vs. present thoughts about axons

Answer 49

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

Question 50

Axon regeneration

Answer 50

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

Question 51

Axon Hillock

Answer 51

Transistion between the soma and axons Function - where the electrcal signals are summed --> get Action potential - Intiator of action potential

Question 52

Structural components of Axons

Answer 52

1. Microtubules 2. Neuroflilaments

Question 53

Microtubules

Answer 53

Long polymers of tubulin dimers - Larger Function - Traffics things up/down axon (Things move on microtubules up/down axon) - Ex. Move mitocondria

Question 54

Nuerofilament

Answer 54

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)

Question 55

Axoplasm

Answer 55

Cytoplasm of Axon

Question 56

Axon Transport

Answer 56

1. Retrograde transport - movement of things from distal to soma - Slow (200 mm/day) and backward - Uses Dynein (moves endosomes + mittocondira + neutrophic signals + toxins + Viruses) 2. 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

Question 57

Nodes of Ravier

Answer 57

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

Question 58

Important characterstic of neurons

Answer 58

Neurons are excitable --> are able to transmit electical signals down axon --> then get the data in the dendrite --> then do things in the soma

Question 59

Action Potential Pumps

Answer 59

1. Na/K pump - let Na out of cell and K into cell --> allows cell to be at resting potential (~ -70 mv) 2. K pump - K goes out of cell 3. 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

Question 60

Generating action potential

Answer 60

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

Question 61

Action potential on mylinated vs. Unmylinated

Answer 61

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

Question 62

Nerve conduction Study

Answer 62

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

Question 63

Nuerotrasmitters types

Answer 63

1. Classical (Ex. Acytlchorline used at nueromuscular junction) 2. Amino Acid (Ex. Glutamate - makes up most of the nuerotransmitters in the brain; GABA) 3. Peptide (Ex. Opiate) 4. Gaseous (Ex. Nitric Oxide)

Question 64

Stiff person syndrome

Answer 64

Person us unable to produce GABA = cells are hyperexcitable = get stiff - Have Antibodies against things that make GABA

Question 65

Why can we differentiate between different forms of tactile touch

Answer 65

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

Question 66

Excitatory and inhibitory buerotransmitters

Answer 66

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

Question 67

Integration

Answer 67

The algebraic summation of inhibitory and excitatory synaptic potentials Occurs in the neuropil (Usually at the initial segments of cell)

Question 68

How can you get an action potential when have multiple things firing using Integration

Answer 68

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

Question 69

Charactristic of Action potnetial

Answer 69

Action potentials are all or nothing

Question 70

Oligio dendrites vs. Schwann cells

Answer 70

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

Question 71

Astrocytes

Answer 71

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

Question 72

What makes the Blood Brain barrier

Answer 72

The tight junctions between endothelial cells make up the BBB

Question 73

Tripartide

Answer 73

Presynapse + Post synapse + Astrocyte Astrocyes = absorbs extra neurotransmitters + release nuerotransmitters

Question 74

Microglia

Answer 74

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)

Question 75

Schwann cells

Answer 75

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

Question 75

Staining peripheral nerves

Answer 75

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)

Question 76

Synaptic Transmission

Answer 76

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

Question 77

Synaptic proteins

Answer 77

Synaptic transmission = complex (Uses many proteins) Uses more than 1000 proteins in presynaptic nerve terminal and over 100 proteins function in exocytosis

Question 78

Choligernic synapse

Answer 78

Image (Left) - shows steps Image (right) - vesicles with Achetylcholine fise with presynatptic --> contents go to synaptic cleft Acytlcholine = important in CNS (implicated in alzheimers)

Question 79

Nueromuscular Junction

Answer 79

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

Question 80

Types of axons

Answer 80

There are different Axon types for different modalities Example - Different types for priopoception + touch + Mechanical/thermal + Pain

Question 81

Types of receptors

Answer 81

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

Question 82

Refractory neurons

Answer 82

Sensory neurons can become refractory (become desensitived) Example - don't feel clothes because nuerons bcome desensituzed

Question 83

Models for nervous system

Answer 83

1. Mice (Ex. have ALS model - ind limbs are lagging) 2. C. Elegans - quick and easy (can model different diseases) 3. Drosphila - Morpholgy can be derived + easy mutated + fast cycle 4. Zebrafish - Can see things developmentally 5. Cell culture - Ex. hiPSC 6. Yeast - East to grow and screen

Question 84

Things to use for biomarkers

Answer 84

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

Question 85

Issue with using blood for biomarkers

Answer 85

Can't always see things - espcially because of Blood Brain Barrier

Question 86

Issue with Biomarkers

Answer 86

Lack reproducibilty - people get different results

Question 87

Recent Rise in gene discovery

Answer 87

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)

Question 88

Discovery of iPSCs

Answer 88

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

Question 89

Versitity of iPSCs

Answer 89

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

Question 90

Oppertunity to idetify mechanism of disease

Answer 90

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

Question 91

Diseases of nervous system

Answer 91

Parkinsons + Alzhemiers + Huntingtons + ALS + epilespy + Ataxia + Multiple sclerosis + Peripheral nueropathy + Neoplasia + Stroke + Infection disease + Prior disease