Physiology Lecture (PNS) Flashcards

Question

Secondary nuerons

Answer 1

Spinal cord nuerons Secondary neurons Decussate (cross the midline) --L axon crosses the midline to the other side of teh spinal cord to go to the thalumus (reason why the left brain controls the right side of body and vica cersa)

Answer 2

Top - Somatic - 1 axon --> goes to the peripheral target and to CNS (to SC) Bottom - Autonomic - 2 nueron system (preganglionic --> ganglion --> postgangliic --> periphery

Answer 3

The area of skin inervated by a single forsal root Each pair of DRG sends an axon to different parts of the body -- creates dermatomes Tractile + pain + termapture dermatomes bounderies can be different

Answer 4

Repsonse of each dorsal root ganglion to different stimuli can be systematically tested and the bounderies of each dermatome can be mapped map dermatimes by recording nerves and see where they innervatate --> see reponse of each DRG to stimuli --> map bounderies of dermatimes

Answer 5

Adjacent dermatomes can overlap because of overlapping adjacent dorsal roots Each DRG sends an axon ---> Axons can branch to cover more area of the skin - at bounderies there can be overlap between where DRG send axons

Answer 6

Mechanocorecpetors (slow adpating) --> Mekel cells + ruffiniing endings Pain/temp (rapidly adapting) --> Meinssner + passinean corpsucles Free nerve endings - not associated with end organs just axon sent to skin - Senses pain + temp

Answer 7

Slow - innervates the area --> nerve first AP during duration of indentation (nerve keeps firing while applying pressure) Rapid - Nerve first during onset and offset (when pressure is applied and taken off) Rapid vs. slow adpating - allow syou to feel uintity of pressure/touch

Answer 8

There are 4 organs in skin innervated by nerves: 1. Meissners corsulcles 2. pasinean corpsucles 3. Ruffini endings 4. Merckles disks Different end organs allow nerve to sense different types of sensation

Answer 9

Afferents enter the spinal cord - DRG axons (blue) + decesning afferent from the brain (green) Nuerons in spinal cord - Projecton uerons (brown) + interneuons (purple_ + effernet neruons (Maroon)

Answer 10

Image - Blue on upper left = dorsal horn ; Green on lower left = ventral horn --> BOTH have axons going to spinal cord (going to different regions of the spinal cord) Image - Right = nuerons within the spinal cord (peripheral axons synapse with spinal cord nuerons_ - Brown line = seocndary axons crossing the midline Axons = have different termmination based on sensation --> you can guess snesory function based on termination - Dorsal horn = termpature + pain - Ventral hron = muscle sensation

Answer 11

Grey matter in spinal cord is subdivided into 10 laminae based on nueronal cytoarchitectire Example - dorsal horn = pain + temperture + itch + touch Example #2 - venral hron = controls muscle

Answer 12

Order - Primary nuerons (Dorsal root ganalion detecting information from peripshery) --> Secondary nuerons (SC _ medual) send nueron to thalmus in the brain --> terta=irary nuerons in the thatmus nucleaus which send axon to cortext in brain --> 4 nuerons in cortext Nerons in somatic = connected ina seriors by their nerve fibers for sensory infomration trasnfering from body to cortext Have seperate pathways to touch/position vs. pain/tempeture

Answer 13

Have two major ascedning pathways sending somatic sensory information to the cortxt: 1. pain and Tempeture 2. tact (touch and vibration) + limb perioperceotion

Answer 14

Sensation of body - controled by nerves inervating muscles Example - close etes and can still touch nose IF have no perioperception = can't stand (Ex. geentic issues where you loose nerves = become paralyzed)

Answer 15

Anterolateral system - Axon goe sto spinal cord --> synapse with DRG --> Axon cross midline --> Axon goes to thalumus --> Axon goes to cortext Acending = goes towards the brain

Answer 16

Dorsal column medial lemniscal system - DRG synapsed with seocndary nueron in Spinal cord --> Axon ascedns but different from atherlolateral

Answer 17

Sensory information is mapped somatotopically in the primary sensory cortex Somatotopically - Adjacent area in the body are represnte dby adjacent areas in the cortex (area of the body is next to area of cortext that controls taht area of the body) ALSO shows strength - bigger area = bigger strength of control - Ex - representation of perioral region (face) and hand is large in human (because relay on hand and face more than other parts)

Answer 18

There are multiple primary maps Maps = anatomically distict - maps are asictaed with different snesory modailitues Make map by probing different areas and seeing where there is movement in body

Answer 19

Part of the somatosensory cortext of rodents Function - sensory inputs from wiskers - Rodents = rely on wiskers for sense Within barrel cortex --> Conatins discerte areas of layer 4 form - layer forms barrels - Can visualize barrels in histologial staining

Answer 20

Woolset and Van der Loos discoevred barraels --> Did Methylene blue staining --> found that 1 barrel structure containes 2500 neuerons arranged in a ring like straucture + 1 barrel processes tactile input form one wisker - # barrels = # of wiskers Barrel = formed 4 days after birth

Answer 21

Barrels are arranged in pattern correspondong to topography of wiskers

Answer 22

Number of barrels = the number of vibrassae (wiskers) on the controlateral side of the face - one barell : 1 wisker relationship

Answer 23

WT mice - 1 barrel = 1 whisker in patter --> row arrangments correlates well Mice with extra whisker = have extra barrel --> IF pluck wisker out the barrel disappears - Shows there are cues from the peripheral (sensory input) --> if lose that peripheral input then lose barrel

Answer 24

The dicrete pattern of wiskers is replicated throughout the central pathways of the trigeminal system BUT the orientation at each station is dufferent - Arrangments (having different orientations) allow organisms to know where on the face the information is being sensed + what kind of sensory information is being received (Ex. wiskers moving in certain directins activate specific nerurons in the corresponding barrel) - Still is always 1:1 ratio - EXCEPTION - the arrangment is not maintained in the trigeminal ganglion Example - Face wiskers have point facing left vs Brinastain have point facigng rigt etc.

Answer 25

Activation of nociceptive nuerons innervating visceral organs is felt as pain elsewhere in the body Example - when have a herat attack (myocordian infarction) or angima --> left arm and chest hurt NOT The heart Hypothesis for why - convergence of visceral and somatic afferents on the same projection nuerons in teh dorsal horn - Convergence of 2 dorsal root ganglion to same neuron in spinal cord

Answer 26

If internal organ has pain = feel it comes from the skin because they synapes to the same secondary nueron in the spinal cord 1 neuron in organ --> SAME secondary nueron in SC 1 nueorn in skin -> SAME secondary nueron in SC

Answer 27

Dorsal root ganalion = stained with 3 markers Eaxch dot in image = 1 nueron Each DRG = has 10-15 nueroms (have many cells in one ganglion) ; Cells are heterogenous - Red nueroms are larger (have biggger cell body - bigger cell body becase sending axon far awat = need to maintain metabolsim on long axon) vs. yellow have smaller cell bodies

Answer 28

1906 - Charles Sherrington postuled the existnce of pain sensing nueron nociceptive nuerons) - Specilated that certain neurons sense pain 1967 - Ed perl and colegues experimentaly demonstarted the esxistence of these nuerons

Answer 29

Cells detecting noxious stimuli capable of casuing tissue injury Nocicpetive nuerons = normally only respind to noxious stimulu NOT innoculous stimuli (wont be active if have gentle touch only sense pain) - Subsets of nociceptive nuerons also mediate itch

Answer 30

Pain sensation is multidemensional with sensory discminiation + cgnitive + evaluative + emotional compoennets - Inlcudes sensory compeoent but also emotional (example - how bad the pain is)

Answer 31

Overall - shows nocireceptors exist Looked at nerves in skin --> record nerve activity --> Add stimulation to the skin When add a blunt probe = no pain even if increase force = no nuerons firring When use needle = painful --> when increase pressure --> nerve fires AP - Add more force = more painful = fires more

Answer 32

NOW = can image nerves instead of recording action potentials Cause nerve to express GcAMP -- Activate the nerve = have flourence - Image - faint lines = nerves --> when apply painful stimulation the nerves light up

Answer 33

1. Large 2. Medium 3. Small

Answer 34

Large diameter cell body Myleinated axons + Axon is thick diamter = fast conductons Fast conduction velocity - when sending Action Potential --> conduscts well = fast conductions = feel sensation instantaneously Invloved in body position + light not painful) touch

Answer 35

Medium diamter cell body Thinly mylinated axons + smaller axon (smaller than large) Medium conduction velocity (slower conduction than large) Invloved in intial sharp pain

Answer 36

Smaller diameter cell body Un-mylinated + axon is thin Slowest conductino velocity Invloved in delay burnig pain - Example - if cut the tail of a dinaosor it would take time for it to feel because slow conduction velocity

Answer 37

Nociceptor is different for different modalities BUT some nociceptors are polymodal menaing they can feel multiple modalities - Different nocicpetors detect different type of pain Example - mechanimcal vs. temperure vs. chemical (chili pepper)

Answer 38

>45 degrees - Feel hot pain <15 degrees - feel cold pain 15-45 = pleansnt

Answer 39

When have injury ATP + ACID + capsaicain (pepper) When screted from cell = painful

Answer 40

1.Volatge gated Na, K, Ca chanels --> essential for generation and propegaion of AP and NT release 2. Ligand gated catino chanles - activated by pain stimuli and depolarize nueron - Ex. - Acid Acivated + ATP activated + Tempetire activated 3. GPCR - activated by molecules and mediate ion chanel acitivities

Answer 41

1. Nociceptor detects stimulus - have volatge gated Na, Ca, K chanels --> allow nerves to do AP and release nuerotransmitters 2. Have ligand gated chanels --> chanels are activated by pain stimulus = depolarized nueron = activates voltage haoted chanel to get AO 3. Have G-protein coupled recetor - Have inhibitory (ex. opiary recetors) --> inhibit pain _ inhibit nueronal activity - Have Activatory (Ex. Prostaglandin) --> make pain worse Ipotentiate channels = worse pain)

Answer 42

Transient receptore poential vanilloid I - a molecule sensor for noxious heat (>42 degrees + Noxious heat)

Answer 43

Previous reserach - showed that capsacain activaes subset of Dorsal Root Ganglions nueorns and induces Ca influx in cells - Culture DRG --> give culture Capcasian --> Activates a subset of DRG (see Ca influx = see activation using Ca sensitive dye) - Add capsacian = get Ca release Experiment = used expression cloning approach into heterologous cells - Generation dorsal root ganglion cDNA library (reverse trasncriped from mRNA from DRGs) --> express different pool of cDNA in heterologous cells --> Monitor capcasian activatiion by Ca imaging - Looking at DRG cDNA that makes cells repond

Answer 44

Blue = heterologous cells IF No DRG genes cDNA = no difference in cells with or without cacaccian Add 1 cDNA library - have certain nuerons that light up when adding CAP Second cDNA library (narrowing down to 1 gene) = epressed one ene --> When add CAP most cels respond

Answer 45

sequenced the cDNA of protein --> found that the protein has every feature of an ion chanel Protein has: 1. 6 trabsmembrane domains 2. 1 pore domian (opens so ions can go into cells) BOTH - show TRPV1 is a chanel

Answer 46

TRPV1 - ion chanel actuvated by capsacian and heat - Expressed in pain sensing neurons (expressed in small diameter niciceptor) In Gain of function exepeiriment - If look a recoding in chanels: 1. Adding CAP = inward current (+ ions go into the cellls) 2. Add heat (>42 degress) = current goes into cells SHOW - chanels repsond to heat and CAP

Answer 47

Did a Loss of Function (LOF) experiment --> delete TRPV1 and look at Ca test TRPV1 defeincent = fails to respond to a speciifc range if nixious heat: 1. WT - respond at 45 degrees 2. Knockout - Don't respond at 45 dgerees BUT at a higher threshold (>45 degrees) a smaller percent of nuerons repsond in WT and a small percent rescpond in knockout --> possible that there is another ion chanel contributing >50 degrees

Answer 48

Behvaioral response to heat is reduced in TRPV1 KO mice When poke hind legs - no difference in WT or KO --> no differences for mechanimcal sensory --> shows TRPV1 is not involoved in mechanical When put tail in hot water (temperture) - See KO take longer to withdraw at 50 degress ; at >5 degrees there is a string delay to withdraw in KO When use hot plate (Temperature) - see difference in KO vs. WT --> KO respond in the end

Answer 49

THink that KO reponde >45 dgerees is because other chanels might also respond to heat = other chanels are compensating = animals can still feel some heat and respond

Answer 50

TRP chanels = molecular sensors of various tempeture and chemicals (cover a spectrum of temperture and chemicals) - Dfferent TRP chanels for difefrent tempertures - Example - TRPV2 = used for >50 degrees - epxlains why KO still repond to temperature>50 degrees - TRPA1 - avtivated ny wasabu + te,p <15 - TRPM8 - <20 degrees + mint = cooling sn

Answer 51

Nociceptive nueroms become sensitized under chronic pain states (ex. tissue injury or inflamaton) --> means that thinsg that would nrammly be les spainful cause strong pain - Example - when gently touc injury = pain (because nocieptor becomes sensitized)

Answer 52

Hyperalgesia = more pain Alldoynia = when a normallly not painful stimulus beccomes painful

Answer 53

1. Increased expression of ions channels --> leads to more channels on the memebrane = detect more pain 2. Increase sensitivity of ion chenals - Example - temperture threshold is lower 3. Reduction in inhibitory ion chanel acitivity

Answer 54

Most sensitization = due to G-protein coupled receptor -- have some release of ATP if H+ or Acid OR released liptes --> Acivates the GPCR on nerves = sensitzes nerve Most receotors of the agents are GPCRs

Answer 55

GPCR signlaing pathway = modulates ion chanel activities Ligand binds to GPCR and get sentization of ion chanels

Answer 56

Bradykinin lowered the temperture threshold of TRPV1 Experiment - Look at receptor on nociceptor --> record nocicpetor - add heat with no bradykinin --> get activation inwards at 42 (Nociceptor was activated by 42) - Add Bradukinin = threshodl shofts to 35 degrees (at a temper where TRPV1 would always be open because normal body temp) Bradykinin = phosphorlates TRPV1 = sentizes chanels.= shifts the temperture threshold

Answer 57

Strengthens synpatic transmission between primary afferent neurons and second order nuerons in the dorsal horn in spinal cord - Enhances pain High requencey noniceptive input increase synaptic strength in a NMDA-dependent manner whicg resemble long term potentiation

Answer 58

1. Pain --> refleces = withdrw + avoidance 2. Itch --> reflex = scratzhing (remove iratant to supress itch) - Induce mechanimcal pain = supress itch + mobilize immune cells

Answer 59

Unpleasant sensation that elicits the desire or relex to scratch - Intiated by small-medium DRG nuerons - Different toes of itch = Histamine (allergy) vs. non-histamine

Answer 60

Pain and itch antagonize each other Scratch = mechanical pain = supressed it Morphine = supress pain = induces itch

Answer 61

Observe mouse sratching behvior in response to a pruiogen - Can give different chemicals or induce different skin conditions to induce itch (Ex. Give histamine + chloroquine + compiund 48/80 + seratonin + cowhage + chronic itch models) - Give compund at the level of rostral back of animal --> if animal tcihes = uses hind paw to sratch --> can record animal for 30 minutes and count how many times scratch

Answer 62

Pain = wiping - uses fore paw to gently wipe Itch = Scratching - use hind paw to scratch Sratch vs. wipe = distigusible (different sensations) Example - giving histamine = get straching and no wiping vs. give Capsaicin have wiping and no scratching

Answer 63

1. Intensity - uses the same popultion --> have one nueron to meidate pain and itch AND will feel different senation depending on the intesity of the stimulatiion - Strong stimulation = pain ; wekaer = itch 2, Labeled line - Two different nueronal popultions (one popultion for pain and one popultion for itch)

Answer 64

Hypoethsis for theory = scientists idetofied ithcinga dn pain spots in skin --> had one spot on skin that gives pain and itch - thought that because this was a small spot it could only be one nueron

Answer 65

Experiment - Activate nerves with electical stimulus 0 see how person feels THEN Increase the frequencey of stimuli --> person will feel a stronger itch but no pain THEN increase frefrequncey more --> intensity of itch increase BUT there is no chnage from itch to pain ***Did the same expeirmnet with pain where they start at a higher frequencey and decrease = people feel less pain but never feel itch

Answer 66

Experiment - record human skin --> apply histamine --> see sensation --> When add Histamine --> Get AP --> person reprots an it --> THEN find subtype of nocicptpr (C-fiber subtype) - C-fiber repsonds to Histamine (thought that C-fiber is an itch specific fiber) THEN did the same experriment where you add Histamine and the C-fibers repsonsed BUT when Add CAP C-fiber still repsonds = NOT itch specific - C Fiber with histadine are slective but not specific for pruritogenic substances

Answer 67

Have MRG expressing nuerons --> expressive MRG on nocicpetors --> nocicpetors repsond to itcj when hadd chloquinon (CQ binds to MRG --> Get itch) - MRG = type of GPCR

Answer 68

Used GMP cre loc --> to get MRG on DRG cells + only to 5% of DRG cells MRG nuerons = respond to pruritogens + Capscacin (Itch + pain) - See nueron in live mouse --> Apply stimulus to paw because neuron sends axon to hind paw --> get reponse to CQ + histamine + CAP = not itch specific

Answer 69

MRG3+ axons only innervate the skin Experiment - lavels nureons using cre loc -- found that nueron axon only goes to the apical surface of the skin not visceral organs

Answer 70

Add toxin to 5% nuerons = ablate (kill 5% nuerons) --> other nuerons are not affected --> then see how animla feels WHEN add CQ = less scratch (itch sensation is reduced = know MRG can mediate irch) Pain (chamical + mechanical + temp) = normal ALL together = no more itch BUT normal pain

Answer 71

Experiment: Activates 5% with MRP and TRVP1 All other uerons knock out TRPV1 ADD CAP - WT = lots of wiping (Lots of pain) + No scratching - TRPV1 knockout = no pain + no scratch - 5% with TRPV1 = only scratch + no pain (witch the quality of the sensation because get scratch with CAP) When have TRPV1 = feel pain not itch???

Answer 72

5% cells and the total have TRPV1 Activate bother popultions = they should feel pain + itch BUT they feel pain ecause you have an interneuon that blocks the itch sensation = only feel pain When you delete the internuon = have lots of itch and no pain Overall - there is an itch nueron and pain specific nueron BUT there is als an inhibitor internuron to modify itch sensation

Answer 73

Can you acheive itch with cap - When add CAP to skin = reach itch nerve fiber first because itch nerve is closer to the skin --> topically apply CAP = get itch BUT when CAP penetrates more you get only pain because pain will inhibit the itch

Answer 74

MargA3 = defines a popultion of itch deetced nuerons in DRG Model - Have pain nuerons and itch nuerons and for snesation where you should feel both pain and itch you only feel pain because there is an internueron that inhibits itch but allows for pain