Midterm 1 (Rachael's Contribution)

Question 1

Ionic Concentrations Inside and Outside Cells

• What are the important ions?
  
  • How do they get to their relative positions?
• What does X- represent?
• ​Where is the separation of charge?
  
  • How many ions are needed?

Answer 1

• Na+, Cl-, K+, Ca++
  
  • More Na+ on the outside
  • More K+ on the inside
  • Cl- on the outside
• Considerable energy expended to put Na+ and K+ into their relative position
• Cl- moves passively in response to the resulting electrical potential difference
• X- represents negatively charged proteins/ions
  
  • paired with positive charges and DO NOT have anything to do with electric potential
• Seperation of charge at the membrane
  
  • very small # of ions to make membrane -70mV
  • Similarly, very small # of ions move to change the electric charge in signaling

Question 2

Development of an Electric Potential Difference

• Movements of ions across membranes are influenced by what two energetic factors?
• Membrane permeable to both Na+ and K+
• Membrane permeable to only K+
• Why does electric potential difference develop

Answer 2

(1) Concentration gradient (2) electric potential difference

• Membrane permeable to both Na+ and K+
  
  • both ions diffuse down concentration gradient
  • since concentration gradients are opposing, membrane potential=0
• Membrane permeable to only K+
  
  • Like nerve and muscle cell
  • Only K+ down concentration gradient
  • Electric potential develops
• Electric potential difference because:
  
  • ion concentrations differ on sides of membrane
  • membrane permeable to only one ion

Question 3

Reaching Equilibrium

• How is equilibrium reached?
• What is equilibrium potential?

Answer 3

• As ions diffuse, the membrane potential is changed. Acts in opposition to the ion diffusion
  
  • Ex: K+ flows into cell, making cell more positive so that less K+ flows in
• Equilibrium Potential: electrical potential difference that exactly counterbalances diffusion due to the concentration difference

Question 4

Equilibrium Potential for K+, Na+, Cl-

• What is the equilibrium potential for each?
• Explain the equilibrium potential for Cl-.
• When is there no net tendency for that ion to move in or out of the cell?

Answer 4

• K+: -90mV
• Na+: +60mV
• Cl-: -70mV
• Cl- is near resting membrane potential because no ATP to keep out of equilibrium.
  
  • Negative interior of cell favor net flow of Cl- out of cell
  • Concentration gradient favors net flow of Cl- into the cell
• No movement of ion when membrane potential is equal to equilibrium potential

Question 5

Changes in Membrane Potential

• A specific ion moving through an open ion channel causes the membrane potential to move towards…
• What if more than one ion is moving through a membrane?

Answer 5

• …the equilibrium potential for that specific ion
• More than one ion moving through membrane…moves towards the average of equilibrium potentials
  
  • More permeable the membrane for an ion, the more the equilibrium potential of that ion will influence the membrane potential
  • ​Ex: Resting membrane potential -70mV because mostly permeable to K+ (-90mV), but also permeable to Na+ (60+mV)

Question 6

Open Channeling Virtual Experiment

1. Resting potential
2. Open Na+ gated ion channel
3. Open Cl- channel
4. Close all channels
5. Open K+ channels

Answer 6

1. Resting Potential
   
   • ​Cl- not actively transported, so equal -70mV
2. ​​Open Na+ gated ion channel
   
   • ​membrane potential becomes more positive
   • gets closer to Na+ equilibrium
3. Open Cl- cahnnel
   
   • ​membrane potential down because closer to Cl- potential
4. Close all channels
   
   • ​Goes back to resting membrane potential
5. ​Open K+ channels
   
   • ​Hyperpolarizers towards K+ equilibrium

Question 7

Receptor Potentials

• What happends in response to deformation of the skin by touch?
• What is receptor potential?
• How do receptor potentials vary?

Answer 7

• touch casues mechanically gated ion channels in dendrites to open
  
  • Positive ions flow in (notably Na+)
• This **depolarization **is called a receptor potential
  
  • ​term only used with afferent neurons
• Receptor potenial varies in amplitude
  
  • depends on size of the sensory stimulus
  • Ex: light touch=few ion channels=smaller receptor potential
• Receptor potentials do not travel
  
  • plasma membrane in axon is a “leaky” conductor of electricity

Question 8

Action Potentials

• When does action potential begin?
• What is action potential referred to as?
• Burning fuse analogy

Answer 8

• Action potentials are traveling nerve impulses
• Begins when the depolarization of a receptor potential is large enough to supass the threshold
• Action potentials are an **all-or-nothing **depolarization
• Burning fuse analogy
  
  • match must reach a certain temperature to light the fuse (threshold)
  • heat from one fuse region light the next region and so on and so forth (traveling)
  • the burning of one region to the next is an all-or-nothing pulse of fire
• Na+/K+ works steadily to store potential energy in concentration gradient
  
  • action potential is a breif pulse powered by a small fraction of this potential energy

Question 9

Postsynaptic Potential

• What happends when an action potenial reaches the presynaptic terminal?
• Two ways that the postsynaptic potential is similar to a receptor potential.
• Summate concept

Answer 9

• Action potential reaches presynaptic terminal and causes release of neurotransmitter
  
  • diffuses across cleft to the postsynaptic neuron
  • Neurotransmitter binds to postsynaptic receptors which leads to the opening of ion channels in another neuron
  • Ions through the ion channels change the membrane potential (postsynaptic potential)
• Postsynaptic potential similarities to receptor potential
  
  1. ​varies in amplitutde (depends on amount of neurotransmitter released)
  2. does not travel
• Need many postsynaptic potenials to occur in a short period of time to summate and depolarize the membrane above threshold

Question 10

• Summary tables of receptor, action and postsynaptic potentials.
• Ions channels that depolarize membrane potential
• Ion channels that tend to prevent the membrane potential from going above threshold

Answer 10

Question 11

Electrode in the sensory dendrite compared to the node of Ranvier

Answer 11

• Sensory dendrite
  
  • mechanical gated ion channels
  • receptor potentials
• Node of Ranvier
  
  • no receptor potentials
  • only action potentials

Question 12

Long Touch

Answer 12

• Know that the electrode is in the sensory dendrite because can see the “hump” of the receptor potential
• Longer touch means that there is a longer receptor potential which equates to many action potentials
• After a while, there is sensory adaptation where the touch is still happening, but nothing is felt

Question 13

Coding Type

• Different types of sesnors project to different places

Answer 13

• different neurons that are specialized
• different classes of afferent neuron
• Temperature
  
  • warm sensor
  • different channels
  • go to different places in brain
  • hot temp open ion channels
  • capcaisin binds to ion channels and opens them
    
    • makes area feel hot
• ​Birds don’t have temperature ion channel
  
  • bird eat chile pepper and disperse seeds wide, rather than mammal not spreading seeds far.

Question 14

Coding Intensity

• Receptor potential
• Action potential

Answer 14

• More intense stimuli means receptor potentials that are bigger in size
• More intense stimuli means action potentials that are more frequent

Question 15

Coding Location

Answer 15

• Orderly projection of axons into the brain

Question 16

Coding Change in Stimulus

Answer 16

• A beginning of stimulus, high frequency, and then frequency drops off
• AKA: **sensory adaptation **
• makes neurons more sensitive to changing stimuli

Question 17

Action Potentials: Ion Channels

Answer 17

• Na+ channels open with depolarization
• @ -50mV, start to open, determines the threshold
• depolarization up to threshold→ some Na+ open→Na+ flows in→depolarize→open more Na+ open
  
  • explosive fashion
• closes by repolarization
  
  • after a milisecond, close on their own
• Explanation of Figure
  
  • depolarization open K+ channel
    
    • slower than Na+ channel
    • K+ flows out→hyperpolarization
    • opening causes K+ to close
  • P=permeability
    
    • opened voltage gate Na+ channels
      
      • membrane potential increases

Question 18

Action Potentials: Conduction

Answer 18

• Mieisners: 50 m/sec
• Upper end= 120 m/sec
• Lower end= 0.1 m/sec
• axon conduct electricity to cause next segment to depolarize
• larger axon=faster action potential b/c + charge flows down cross section much quicker
  
  • invertebrates: no myelin, need the be much bigger

Question 19

Action Potential: Myelinations

Answer 19

• Speed up conduction
• Not need to increase axon
• Goes between each node of Ranvier
• Prevents electric current from leaking out
• Phospholipid bilayer of schwan cells wraps around, creating many layers
  
  • Proteins are made to organize myelin
  • No proteins=neurological disorder

Question 20

Na+ Channel Blockers

Answer 20

• Stop Action potentials
• Lidocaine
  
  • Local anesthetic
  • work at low concentrations, so if get into ciruclation, won’t stop heart
• Tetrodotoxin
  
  • puffer fish toxin
  • fish in fugu sushi
• Red Tide

Question 21

Peripherary Neuropathy: size of axons affected

Answer 21

• small axons
  
  • C unmyelinated fibers andA-delta fibers
  • pain sensors in the skin and to autonomic neurons
• large sensory fibers
  
  • A-alpha and A-beta fibers
  • proprioception, vibration sensation, and reduced muscle-stretch reflexes.

Question 22

Axonal Neuropathy

• What are some causes?
• What axons are affected in DM?

Answer 22

• Most common
• Diabetes mellitus/impaired glucose tolerance
  
  • early sign
    
    • burning/tingling sensation in feet, paresthesias
    • mild stimuli cause pain,** hyperalgesia**
    • ordinarily non-painful stimuli causes pain, ** allodynia**
  • ​usually small axon (pain afferents) initially
  • affects longest axons first (feet/fingertips)
  • symmetric
  • later, longer axons are involved, causing numbness
• Alcholism, Vitamin B12 deficiency, leprosy bacillus

Question 23

Guillain-Barre Syndrome

Answer 23

• Demyelinating
• Peripheral neuropathy
• Follows after an infection. Flu like symptoms
• Feel weakness a few weeks after
• Paralyisis is a symptom
  
  • motor and sensory deficits are found and result from inflammation and subsequent demyelination of peripheral nerves
  • starts in legs and works its way up to arms
• myelin attacked by immune system
  
  • Accumulations of lymphocytes and monocytes around nerve
• put on respirator to breathe
• most patients fully recover within a few weeks and can return to work in a few months
• Incidence increases with age

Question 24

Charcot-Marie-Tooth disease

Answer 24

• Genetic
• Demyleination
• weakness, paralysis
  
  • motor and sensory deficits occur
• High foot arch as some muscle contract
• Most commonly shows up during adolescence
• diagnosed with nerve conduction studies and a nerve biopsy
  
  • genetic tests as well

Question 25

Bell’s palsy

Answer 25

• ​demylinating
• peripheral neuropathy
• Inflammation and swelling of facial nerve (6th cranial nerve, goes to brain rather than spine)
• Shows up spontaneously
• Usually improves in a month or two
• Nerve goes through small foramen in temporal bone
• Occurs on one side, droopy face on one side

Question 26

Carpal tunnel syndrome

Answer 26

• Demylenating
• Peripheral neuropathy
• swelling that presses on median nerve and tendons
• can do nerve conduction studies
• sometimes axonal/myelination
  
  • starts as demyelination and then turns into axonal
• symptoms on index and middle finger

Question 27

What is Multiple Sclerosis

Answer 27

• Central nervous system neuropathy
• Demyelination (many areas of the brain can be affected)
  
  • scattered foci
  • replaced by plaques of hardened tissue that can be seen through MRI
• Autoimmune
• Relapsing/Remitting

Question 28

Multiple Sclerosis: Symptoms

Answer 28

• In 30’s when symptoms first appear
• First symptoms:
  
  • sensory and motor
  • optic neuritis
    
    • visual disturbances
    • flashing lights with electrodes on occipital lobe to look for disturbances
  • diplopia
    
    • double vision
  • nystagmus
    
    • fast uncontrollable movements of eye
  • paresthesias, ataxia, muscle weakness
• ​​​Relapse/Remitting in beginning and then later on turns into progressive with increasing axonal and neuronal loss
• 3% chance each year of going into progressive state
• Takes ~20 years to go to progressive state
• With time, increasingly severe symptoms, including paralysis, difficulty speaking, emotional problems, memory loss and autonomic problems.
  
  • Symptoms can encompass most functions of the nervous system.

Question 29

Multiple Sclerosis: Diagnosis

Answer 29

• MRI imaging with gadolinium
  
  • ​administered IV
  • traverse the abnormal, leaky endothelium at the plaques
  • creates bright spot on MRI
• Record visual evoked potential
  
  • similar to that of an electroencephalogram
  • taken during repetitive visual stimuli
  • Optic neuritis is suspected with pain in the eye and disrupted vision
• lumbar puncture
  
  • Test cerebrospinal fluid for signs of inflammation and certain antibodies
  • antibodies against myelin basic proteins
  • Ab levels don’t coordinate well with the progression of MS

Question 30

Multiple Sclerosis: Sequence of Events in the Plaques

• Environmental factors
• Relapsing phase
  *

Answer 30

• genetic and environmental factors play important roles
• Highest in Scotland, more common in temperate locations
  
  • Vitamin D involvement?
• correlation with infection by the Epstein-Barr virus
  
  • initiate MS?
  • microbe environment influencing Ab production?
• Relapsing Phase
  
  • bursts of inflammation in foci in the white matter
  • blood-brain barrier is disrupted in these areas
  • T cells and macrophages are prominent in the lesions
  • CD4+ T cells are type I, which produce INF-gamma and induce significant inflammation
• initial, focal inflammation is ultimately responsible for the later cascade of pathology that causes the long-term disability

Question 31

Alemtuzumab

Answer 31

• Monoclonal Antibody
• Binds to a receptor on T Cell
• Used in early MS
• Prevents long term disability
• Significant immunological side effects

Question 32

Multiple Sclerosis: Effects on Axons

Answer 32

• Myelin sheath degenerates
  
  • action potentials slow and ultimately stop
• new Na+ channels may then be placed in membrane previously covered by myelin
  
  • axons function as if they are unmyelinated (slow conduction)
• In early phases, partial remyelination
  
  • axonscan regain function
• As conduction becomes marginal
  
  • upset by increases in body temperature​​
  • speeds the opening and closing of ion channels (shortening the action potential)
  • May be enough to block the action potential

Question 33

Multiple Sclerosis: Treatments

Answer 33

• During an acute relapse
  
  • corticosteroids to control inflammation/immune
  • **disease modifying **treatments (DMARD)
    
    • disease modifying anti-rhuemetic drug
    • slow the progression
    • interferon beta-1
    • Glatiramer
    • Natalizumab
    • mitoxantrone
    • fingolimod

Question 34

MS treatment: interferon beta-1

Answer 34

• Cytokine
• modify the immune response
• anti-inflammatory
• improving the integrity of the blood brain barrier
• Flu-like side effects
• for ongoing treatment

Question 35

MS treatment: Glatiramer

Answer 35

• synthetic polypeptides that alters T cell function
• possibly mimick/modify myelin proteins
• must be injected regularly

Question 36

MS treatment: Natalizumab

Answer 36

• Monoclonal antibody
• blocks adhesion molecules in the endothelium
• prevents entry of inflammatory cells into the lesion
• more effective than interferon beta-1
• small but significant risk of a serious immunological disorder

Question 37

MS treatment: mitoxantrone

Answer 37

• Immunosuppresant
• Blocks DNA synthesis
• Used later in disease progression
  
  • has serious side effects
    
    • cardiotoxicity
• ​Also used in cancer chemotherapy

Question 38

MS treatment: fingolimod

Answer 38

• 2010
• Only oral treatment
• phospholipid from chemical modification of Chinese medicine fungi
• suppress/modify immune response
• Goes to lymph node and makes it harder for lymphocytes to leave

Question 39

Structure of Synapses

Answer 39

• Antibody bind to synapse=bright green
• Bright green=presynaptic terminal
• Each presynaptic terminal is full of vessicles
• 1st neuron is the presynaptic neuron, neuron recieving information is the postsynaptic neuron
• Synapses the site of neuronal decision making
  
  • multiple presynaptic action potentials required for postsynaptic action potential ​
  • sequence of action potentials in postsynaptic is not the same as in the presynaptic

Question 40

Neurotransmitter Release

Answer 40

• Vessicles release neurotransmitter in 1 millisecond after action potential (Ca++ entry)
• SNARE docks vessicle into position to be ready to be released
  
  • v-SNARE on vessicle
  • t-SNARE on terminal membrane
• Ca+ causes exocytosis and membrane to bind
• occasionally a vesicle will release spontaneously
  
  • not make big difference

Question 41

Drugs/Toxins acting on SNARE

Answer 41

• Botulism
  
  • causes neurotramistter to leak out presynaptic neuron and not go into synapse
• Tetanus toxin
  
  • works at spinal level
  • toxin in neuron, travels up axon, into spinal cell body, into general area of spinal cord and taken up by presynaptic cell
  • post synaptic gets very excited, cause of mucle contractions

Question 42

After Neurotransmitter Release (3 things)

Answer 42

1. Recycling of neurotransmitter/vessicles
2. After NT release, vessicle pops back in
3. Axonal Transport
   
   • ​protein/peptide NT
     
     • vessicle in cell body and moved down
     • Ex: oxytocin and vasopressin
       
       • made in cell body in hypothalamus and travel down axon
   • ​Source Ca++
     
     • voltage gated Ca++ channel

Question 43

Surely vesicles are used up quickly. Where do you suppose new vesicles come from?

Answer 43

• bud off from endosome in presynaptic terminal
• transporters in membrane fill the vessicles with NT

Question 44

In some cases a protein is released along with the neurotransmitter. How does that get into the vesicle?

Answer 44

• ​vessicles travel down the axon from the cell body where the rough ER is found
• small molecular NT can then be added in the presynaptic terminal

Question 45

What happens to the neurotransmitter in the synaptic cleft?

Answer 45

• within a few milliseconds, transporters in the membrane of the presynaptic terminal transfer it out of the cleft into the cytosol, where it can be reused
• block the NT transporter, then increase NT duration of action
• Exception: Ach
  
  • broken down by acetylcholinesterase

Question 46

three possible receptors on the postsynaptic membrane

Answer 46

1. ligand gated ion channel
   
   • ​opened directly by NT
   • produces a fast postsynaptic potential
2. ​NT bind seven transmembrane domain receptor, activating a trimeric G protein
   
   • subunits can skate under the membrane to open ion channels
   • slow postsynaptic potentials
     
     • ​type that adrenergic and muscarinic receptors in the autonomic nervous system produce
     • Ex: control of heart rate, alertness, sleep and emotions
   • potentially could also activate enzymes, such as adenylyl cyclase, that produce further intracellular actions
3. NMDA receptor
   
   • ​​slow postsynaptic receptor
   • ligand gated ion channel
   • small amount of glutamate released as the neurotransmitter will not open the channel
     
     • need pop, pop, pop, pop etc.
   • Mg++ ion acts as a cork and blocks the channel
     
     • only leaves with persistent depolarization
     • Allows Ca++ into the cell, causing more prolonged changes
   • ​important for memory

Question 47

Fast Excitatory Postsynaptic Potentials

Answer 47

• milliseconds
• last longer than action potential, but not much longer
• caused by NT opening ligand gated channel
  
  • Na+/capsacian go through ion channel
• 5 subunits
• ​Meisner corpsucle
  
  • NT=glutamate
  • When NT binds, channel opens
• Need many presynaptic action potentials to reach threshold of postsynaptic terminal
  
  • summation
• In the action potential, the “zig zag” before the action potential represent a few voltage gated Na+ channels opening, then they all open, creating the action potential
• A hard touch (symbolized by multiple stars) keeps the membrane above threshold.
• A toxing that blocks Na+-voltage gated channel works postsynaptically.
  
  • postsynaptic potential will go above threshold, but there will be no action potential

Question 48

Slow Excitatory Postsynaptic Potentials (EPSP)

Answer 48

• Takes seconds
• Important for emotions, alterness (reacting to alarm clock)
• 7 transmembrane
• Also NMDA
  
  • NOT 7 transmembrane
• NT binds 7 transmembrane domain
  
  • Ach bind to heart, slows HR
    
    • Makes K+ go through ion channel
  • Beta and gamma: open ion channnel
  • alpha: activates enzymes
    
    • ex: cyclic amp, open ion channel

Question 49

Inhibitory Postsynaptic Potential (IPSP)

Answer 49

• Like EPSP
• ions through a channel
  
  • EPSP: Na+ & Ca++
    
    • equilibrium potential of these are above threshold
  • IPSP: K+ & Cl-
    
    • equilibrium potential of these are below threshold
    • hold membrane potential below threshold
• spinal cord has IPSP
  
  • remove to excite just the neurons wanted

Question 50

Summation of Postsynaptic Potentials

Answer 50

• hundreds or even thousands of presynaptic terminals connect with a postsynaptic neuron
• postsynaptic potentials caused by all these presynaptic terminals add together and this is called summation
• temporal: summing EPSP b/c a lot occur close together (pop pop pop)
• spacial: add EPSP
• If sum above threshold, then action potential

Question 51

Skin Afferents

Answer 51

• ​C afferents
  
  • ​unmyelinated afferents
  • pain, temperature
  • 0.5 to 2.0 meters/sec
• A-delta fibers
  
  • smallest and slowest
  • thinly myelinated
  • sharp, quick pain, crude touch and temperature
  • 5 to 30 meters/sec
• A-beta fibers
  
  • large, fast
  • myelinated
  • 35 and 75 meters/sec
  • Meisnner’s and Pacinian corpuscles
    
    • rapidly adapting touch afferents
  • Merkel’s discs
    
    • slowly adapting touch afferents

Question 52

Muscle and Joint Afferents

Answer 52

• Proprioception
  
  • able to understand position of limbs
• Muscle spindles
  
  • ​scattered throughout skeletal muscle
  • small group of small muscle fibers enclosed in a connective tissue capsule
  • monitor muscle length
  • A-alpha fibers (type Ia)
    
    • 80 to 120 meters/sec
    • fastest axons in the body.
• ​Golgi tendon organs
  
  • lie at the junction between a muscle and its tendons
  • sensory dendrites embedded in a connective tissue structure
  • A-alpha fibers (type Ib)
    
    • ​ monitor muscle tension
    • conduct slower than muscle spindle afferents

Question 53

Neurotransmitters of Afferent Neurons

Answer 53

• C fibers release glutamate
  
  • can have both fast actions by binding to a five subunit ligand gated ion channel and slow actions actions by binding to an NMDA receptor
  • release peptides, such as subtance P
• All myelinated afferent neurons release glutamate as NT,
  
  • fast neurotransmitter binding to the five subunit ligand-gated ion channel.

Question 54

Sensors in Viscera

Answer 54

• Pain
  
  • From decreased blood flow
  • Local ECF
    
    • Increase H+
    • INcrease K+ (from damaged cell)
  • stretch

Question 55

Sensory Information Traveling Into the CNS

Answer 55

• Spinal cord
  
  • dorsal columns (developed in humans)
    
    • 3 neuron minimum
    • fine touch, proproception
    • up medulla (on same side)
      
      • in medulla, crosses to other side→thalamus→cerebral cortex
  • antereolateral tract (on L, carry info from R side)​
    
    • More ancient
    • pain, temp, crude touch
    • synpase in dorsal horn
    • axon cross at spinal level
    • up to thalamus→cerbral cortex
• ​Brain has somatosensory organization

Question 56

Tabes dorsalis

Answer 56

• tertiary syphilis
• damage to dorsal spinal column
• have pain, temp, crude touch
• NOT have proprioception

Question 57

Characteristics of Pain Sensors

Answer 57

• A-delta fibers
  
  • myelinated
    
    • smallest and slowest of myelinated
  • 5-30 M/sec
  • sharp, bright pain
  • fades quickly
  • acute pain
  • NT=glutamate
  • mechanical/temperature stimuli
  • fast, five subunit ligand gated ion channnels
• C fibers
  
  • unmyelinated
  • 0.1-1 M/sec
  • “burning” pain, delayed sensation
  • persistant, chronic
  • NT=glutamate, peptide, substance P
  • fast, five subunit ligand gated ion channels and NMDA receptors
  • inflammation
  • receptor for capcaisin found in C fibers
  • nerve ending degeneration
    
    • diabetic neuropathy (peripheral)

Question 58

C fibers, Substance P and Inflammation

Answer 58

• C fibers interact with the process of inflammation
• action potentials in certain branches of an afferent neuron are moving peripherally
  
  • axon reflex
  • sensation of pain in CNS and release of substance P locally
    
    • histamine release and dilation of blood vessels.

Question 59

Reduction in the Perception of Pain: gate controlled hypothesis

Answer 59

• gate control theory
  
  • ​rub muscle (A-beta fibers) to dull pain
  • large, mechanically sensitive afferents excite interneurons that in turn inhibit the neurons that carry pain information from the dorsal horns to the brain
• transcutaneous electrical stimulation (TENS)
  
  • weak electrical current is applied to the skin near the site of pain

Question 60

Reduction in the Perception of Pain: opiates

Answer 60

• analgesia produced by morphine and other related opiates
• bind to opioid receptors found in many areas of the brain
  
  • ​opiod receptors are 7TMD to G protein
  • concentrated in the periaqueductal gray, medulla, and dorsal horns
• opioid peptides
  
  • molecules that naturally activate the opiod receptors
  • enkephalins, dynorphin and beta-endorphin
  • enkephalins from PAG to the dorsal horn, release enkephalins from interneuron to inhibit pain

Question 61

Neuropathic Pain

Answer 61

• due to altered neuronal properties

Question 62

“wind-up” pain

Answer 62

• continued painful stimulus
  
  • pain gets greater and greater
• early morphine use, less likely to get neuropathic pain
  
  • double edged sword: increased addicition/abuse
• Factor “class story”
  
  • steady release of substance P
  • diffuse
  • lead to cellular changes such as increased neuronal sprouting
  • Other cellular changes might follow from activation of NMDA receptors
    
    • prolonged depolarization
    • resulting influx of Ca++ could activate enzymes (such as nitric oxide synthase) or trigger other long lasting cellular changes
• **​​​neuronal remodeling **

Question 63

phantom limb pain

Answer 63

• from damaging or cutting nerves
• ulnar nerve, pain in pinky
  
  • no pinky, still pain
• cutting nerves causes lots of depolarization
• phantom hand goes into prosthetic
  
  • phantom sensation for better use of prosthesis
• put lidocaine on nerves as cut them during amputation to prevent action potential

Question 64

deafferentation pain

Answer 64

• neurons not getting any input
• neurons are remodeled

Question 65

Sympathetically maintained pain

Answer 65

• blocking the sympathetic nervous system helps relieve the pain
• interconnections between efferent sympathetic outflow and incoming afferent pain information
• In addition to other types of pain medications, sympathetic ganglia may be blocked as well as circulating norepinephrine and epinephrine
• Need to be treated because they can become irreversible
  
  • altered skin blood flow,edema, or abnormal sweating
  • nail/hair growth and degeneration in muscle/bone
  • can spread

Question 66

Visceral Pain

Answer 66

• Somatic (skin)→useful to know exactly where pain is to remove stimuli
• Viscera
  
  • no direct somatotopic organization
  • coverges on somatic pain
  • feels like it’s on the skin
    
    • ex: heart attack pain on skin above heart as well as on the arm
  • air on diaphragm, pain on shoulder

Question 67

Pain Drugs

Answer 67

• For nocioceptive pain
  
  • NSAID
  • acetaminophen
  • opiates
• For neuropathic pain
  
  • tricyclic antidepressants
    
    • block reuptake (norepinephrine, seratonin)
    • neurotransmitter=more effective
  • anticonvulsants
    
    • gabapentin
  • NMDA antagonists
    
    • memantine

Question 68

Sensory information is carried up the spinal cord to the brain via two pathways

Answer 68

• dorsal columns
  
  • ​fine touch and proprioception
• anterolateral tracts
  
  • ​pain, temperature and crude touch

Question 69

Dorsal Columns

Answer 69

• afferent axon entering the dorsal horn and then continuing up the dorsal column on the same side to the medulla
• In the medulla, the afferent neuron forms a synapse with a second neuron, whose axon crosses over in the medulla to the other side and continues up to the thalamus.
• Finally, a third neuron carries the information to the cerebral cortex. The specific region is the somatosensory cortex.

Question 70

Anterolateral Tracts

Answer 70

• branch of an afferent axon entering the dorsal horn. In the dorsal horn, the afferent neuron forms a synapse with a second neuron.
• The axon of this second neuron then crosses over at the spinal level and enters the anterolateral tract, where it continues all the way to the thalamus.
• Finally, a third neuron carries the information from the thalmus to the cerebral cortex. The specific region is the somatosensory cortex.

Question 71

Definition of Motor Unit`

Answer 71

• one somatic efferent (motor) neuron and all of the muscle fibers (cells) that it innervates
• below, two motor units are illustrated diagrammatically
• efferent axon enters the muscle, it branches and forms synapses with a number of muscle fibers.
  
  • no overlap in the innervation of the muscle fibers by different efferent neurons
• gastrocnemius=by hundreds of efferent neurons
  
  • each efferent neuron innervates hundreds, or even thousands, of individual muscle fibers.

Question 72

Motor Units and the Contractions of Whole Muscles

Answer 72

• synapse between the efferent neuron and one muscle fiber
  
  • huge
  • always releases enough acetylcholine to depolarize the muscle fiber above threshold.
• one action potential in the efferent neuron leads to one action potential in all of the muscle fibers in the motor unit.
  
  • one brief, all-or-nothing contraction of all of the muscle fibers in the motor unit
    
    • twitch.
• each motor unit is either relaxed or each presynaptic action potential causes an action potential in all of the muscle fibers of the motor unit, causing them all to contract at once.
• In the whole muscle, contractions of different strengths necessarily are created by activating different numbers of motor units.

Question 73

Fast vs. Slow Motor Units

Answer 73

• Fast
  
  • 2nd recruited
  • Large muscle fibers
  • Larger efferent neurons
  • Much glycongen and glycogen splitting enzymes
  • Fewer mitochondria
  • Few capillaries
• Slow
  
  • 1st recruited
  • Smaller muscle fibers
  • less glycogen and glycogen splitting enzymes
  • lots of mitochondria
  • many capillaries
  • myoglobin
• Most muscles are a mixture
  
  • postural muscles are mostly slow
  • extraocular muscles of eye are all fast

Question 74

Fast vs. Slow Motor Units: Size of Efferent Neurons and Muscle Fibers

Answer 74

• type of the efferent neuron determines the characteristics of the muscle fibers that it innervates
  
  • muscle fibers innervated by small efferent neurons are also small
• small motor neurons are the easiest to excite above threshold
• smallest type of contraction of the muscle, the smallest motor neurons and the smallest muscle fibers begin contracting
  
  • progressively stronger contractions, the intermediate and then the large efferent neurons successively add their contributions to the contraction.
• recruitment of larger and larger motor units

Question 75

Fast vs. Slow Motor Units: The type of myosin expressed

Answer 75

• rate at which the myosin uses ATP
• slow muscle fibers contract relatively slowly, use ATP slowly

Question 76

Fast vs. Slow Motor Units: Support of Oxidative Phosphorylation

Answer 76

• use ATP relatively slowly, the circulatory system usually can deliver enough oxygen to allow oxidative phosphorylation to generate the required ATP
• many capiallaries, many mitochondria, high myoglobin
  
  • myoglobin binds oxygen and speeds it diffusion into the muscle fibers
• muscle fibers are small, which also allows for rapid diffusion of oxygen to the interior of the muscle fibers.

Question 77

Fast vs. Slow Motor Units: Support of Glycolysis

Answer 77

• fast rely on glycolysis to generate most of the ATP
• release lactic acid into the blood
• lactic acid is either converted to glucose in the liver or used by the slow muscle fibers

Question 78

Fast vs. Slow Motor Units: Comparison Table

Answer 78

Question 79

Reflex Arc

Answer 79

• consists of an afferent pathway, a portion of the central nervous system, and an efferent pathway
• stimulus to a sensor leads, via a reflex arc, to a response in an effector
• direct and reproducible relationship between afferent and efferent

Question 80

Stretch Reflex

Answer 80

• control lengthin skeletal muscles
• fastest reflex in body
• afferent neuron make direct synaptic contact with the efferent neuron
• sensor is the muscle spindle
• efferent neuron here goes back to the very same muscle that contains the muscle spindle
  *

Question 81

Reciprocal Innervation

Answer 81

• efferent neurons that innervate an antagonist muscle
  
  • inhibitory interneuron lies in the pathway
  • ​prevents the antagonist from preventing the action of the stretch reflex
• principle of reciprocal innervation is part of motor reflexes in general
  
  • Exitation of the muscle in question tends to inhibit the contraction of antagonists

Question 82

Golgi Tendon Organ Reflex

Answer 82

• control tension in a muscle
• An inhibitory interneuron connects the afferent neuron to the efferent neuron going back to the same muscle
• increasing tension in muscles sends more efferent action potentials to reduce tension

Question 83

Pain Withdrawal Reflex

Answer 83

• pain sensors in a limb tends to exite efferent neurons going to the various flexor muscles in the limb
• principle of reciprocal innervation implies that the extensor muscles in the same limb are inhibited
  
  • extensor muscles in the opposite limb are excited
  • crossed extension reflex

Question 84

Parkinson’s Disease

Answer 84

• begins at age 60
• idiopathic
• due to degeneration of a set of neurons in the midbrain called the substantia nigra
  
  • project to the **basal ganglia **and release dopamine
• Lewy Bodies
  
  • ** protein aggregations** of the protein alpha-synuclein in neurons of substantia nigra

Question 85

Parkinson’s Disease: Symptoms

Answer 85

• Bradykinesia:
  
  • ​slowness of movement
  • initially as a weakness or stiffness in one limb
  • becomes more and more difficult to initiate movement, the patient will start to show akinesia, or a lack of movement
    
    • gives the patient the appearance of having a mask-like, frozen look.
• Hypertonia
  
  • excessive muscle tone
  • rigidity or stiffness.
• Resting tremor
  
  • usually disappears when the patient undertakes a voluntary movement with the limb
• stooped posture and slow, shuffling gait.
• symptoms may start off as asymmetric

Question 86

Neurodegeneration in Parkinson’s Disease

Answer 86

• degeneration of dopaminergic neurons in the substantia nigra of the midbrain
  
  • These neurons send axons to the basal ganglia
• interconnections of the basal ganglia
  
  • inputs from multiple cortical areas, and then send output to the motor cortex via the thalamus
  • integrates multiple inputs to modulate the output of the motor cortex
• substantia nigra is interconnected with areas in the basal ganglia
  
  • some excitatory and some inhibitory
  • loss of dopaminergic input from the substantia nigra alters the output from the basal ganglia to the motor cortex

Question 87

Parkinson’s Disease: Drug Treatments

Answer 87

• aimed at restoring or increasing lost dopamine in the basal ganglia
• L-dopa (also known as** levodopa**)
  
  • precursor to dopamine
  • can be given orally, crosses blood-brain barrier
• dopamine agonists
  
  • prolong the action of dopamine by blocking its uptake or inhibiting enzymes involved in its breakdown
  • side effect, dyskinesia, uncontrolled involuntary movements

Question 88

Parkinson’s Disease: Surgical Treatments

Answer 88

• create a lesion in particular parts of the thalamus or basal ganglia that become overactive in Parkinson’s disease
• deep brain stimulation
  
  • Electrodes are implanted into particular locations
  • mode of action of DBS is still not clear​
  • modulates basal ganglia output that has been disrupted due to the loss of dopaminergic input from the substantia nigra.

Question 89

Genetics and Parkinson’s Disease

Answer 89

• roughly 5% of cases of Parkinson’s disease are familial
• locus PARK1, which leads to a mutation in the protein coding for alpha-synuclein
• function of alpha-synuclein is not entirely clear
  
  • may be important in maintaining the integrity of synaptic terminals

Question 90

Amyotrophic Lateral Sclerosis

Answer 90

• degeneration of “lower motor neurons” and “upper motor neurons”
  
  • lower: somatic efferent neurons that directly innervate skeletal muscles
  • upper: neurons in the cerebral cortex that control the lower motor neurons
• 3-5 year survival
• lower motor neuron: muscle atrophy, weakness and fasciculations
  
  • individual motor units spontaneously contracting as their degenerating efferent neurons spontaneously depolarize
• upper motor neuron: overactive stretch reflexes and other types of hyperreflexia such as **clonus **and the Babinski sign
• most idiopathic
• some of genetic though to be caused by mutation in gene for superoxide dismutase
  
  • gains toxic functions
• Caspases become activated, leading to apoptosis of the neurons
• Aggregations of abnormal protein are present.​

Question 91

Huntington’s Disease

Answer 91

• genetic disorder
• show various spontaneous muscle movements
• intellectual and emotion problems
• involuntary somatic muscle movements can become nearly continual
  
  • chorea: “dance” like movements of limbs and face
• single dominant gene that has extra bases at one end
  
  • protien called huntington
  • disrupts transcription of other genes,
  • serious deficits in mitochondrial function and in control of oxygen radicals
• No cure or treatment

Question 92

Cerebrovascular Accidents

Answer 92

• Most often caused by ischemia
• causes damage to localized regions of the brain

Question 93

transient ischemic attack (TIA).

Answer 93

If the event is brief (less than a half hour) and the symptoms reversible

Question 94

stroke

Answer 94

• CVA with permanent damage
• cells directly affected by the blocked blood vessels die via **necrosis **
  
  • outward diffusion of the neurotransmitter glutamate causes these neurons to die via **apoptosis **
  • caspases are activated by a **steady increase in intracellular Ca++. **
• paralysis on the opposite side of the body
• If stroke is on the left side, aphasia (difficulty with language)
• can also be caused by a hemorrage
  
  • long standing high blood pressure and atherosclerosis

Question 95

Epilepsy

Answer 95

• recurrent, disorderly discharge of nervous tissue
• altered consciousness, improper motor activity, distorted sensory perceptions or inappropriate behavior

Question 96

partial seizures

Answer 96

• begin at a specific area in the brain called a **focus **
• neurons tend to produce spontaneous bursts of actions potentials, which spread out into surrounding neurons
• the hippocampus and other parts of the “limbic system” are unusally prone to epilepsy
• partial seizure beginning in the “limbic system” often begins with a hallucination of an unpleasant odor and sensations of familiarity (deja-vu) or of strangeness
• Changes in mood are also characteristic and include anger, anxiety or loneliness. Auditory and visual hallucinations may occur, along with other sensations commonly reported to be “indescribable”.

Question 97

generalized seizures,

Answer 97

synchronous discharges in both cerebral hemispheres

Question 98

absence seizures

Answer 98

• consciousness is lost for 10 to 30 seconds
• accompanied often by eyelid flutterings
• suddenly stop any activity and then resume when the seizure is over.

Question 99

tonic-clonic seizure

Answer 99

• begins in some cases with an aura, which is a sensory hallucination such as a smell or light.
• patient then cries out, loses consciousness and intense, convulsive jerking of the muscles begins
• bladder and bowel may empty and biting of the tongue is common
• After two to five minutes the seizure ends, usually followed by a prolonged period of confusion.
• The patient is typically fully conscious within 15 to 60 minutes

Question 100

Axonal Transport of Viruses

Answer 100

• herpes simplex virus, for example, tends to reside in a cluster of cell bodies of sensory neurons (the trigeminal ganglion) just outside the brain
• virus to move out along the afferent axons to the lips, where the virus produces the “cold sores” characteristic of the infection
• herpes zoster virus behaves similarly but by contrast is usually confined to cell bodies of sensory neurons at the spinal level
• rabies virus is an example of a virus that moves in the opposite direction, towards the central nervous system

Question 101

Botulism Toxin

Answer 101

• prevents the release of the transmitter acetylcholine from presynaptic terminals by cleaving one of several SNARE proteins
• injected into muscles to reduce unwanted contractions (dystonia)

Question 102

Neuromuscular Blocking Agents.

Answer 102

• interfer with neuromuscular transmission
• Succinylcholine is a commonly used depolarizing neuromuscular blocking agent
  
  • relax skeletal muscles during surgery
  • succinylcholine is actually an agonist, but the channel remains open only very briefly before moving to a closed conformation
• **curare **
  
  • nondepolarizing blocking agent
  • binds very specifically to the acetylcholine receptor, but does not open the channel. ** **

Question 103

Prolonged Transmitter Action

Answer 103

• interfer with the removal of a neurotransmitter from the synaptic cleft
• cholinesterase inhibitors
  
  • treat myasthenia gravis and Alzheimer’s disease
  • Nerve gases and certain insecticides
• prolonged by blocking the reuptake transporters
  
  • Cocaine prevents presynaptic terminals from taking up the transmitter norepinephrine
  • fluoxetine (Prozac) block the reuptake of the serotonin

Question 104

Enhanced Transmitter Action

Answer 104

• bind to separate sites on the GABA receptor and thereby increase the effectiveness of GABA
• benzodiazepines such as diazepam (Valium), barbituates, and ethanol
• increasing inhibition in the central nervous system

Question 105

Blocking Inhibition

Answer 105

• Strychnine binds to and blocks the postsynaptic receptor for glycine
  
  • major inhibitory transmitter in the spinal cord and brain
  • increases excitation of the central nervous system.
• first the face and neck become stiff and even minor sensory stimuli tend to produce violent movements
• Convulsions in the strongest muscles
• Eventually stop breathing

Question 106

Nocioceptive Pain vs. Neurological Pain

Answer 106

• Nocicoceptive Pain:
  
  • Symptoms: Aching, stabbing
  • Signs: tenderness, swelling, warmth, erythema, edema, aggrevated by movement
• Neuropathic pain:
  
  • Symptoms: Burning, lancinating, electric, allodynia
  • Signs: Numbness or weakness in local distribution, Abnormal surface temperature

Question 107

Duchenne Muscular Dystophy

Answer 107

• one out of every 3,500 males born
• At first, muscle fibers are repaired as satellite cells fuse with the damaged cells
  
  • capacity exhausted and muscles waste away
  • fatty tissue infiltrates
• defects in the gene for dystrophin
  
  • intracellular structural protein normally found near the plasma membrane of skeletal muscle fibers
• defective dystrophin allows continual influx of Ca++, which activates an intracellular protease that damages the myofibrils.

Question 108

Myasthenia Gravis

Answer 108

• number of acetylcholine receptors is usually only about 30% to 50%
• neuromuscular transmission often fails
• Muscles around the eyes are those most commonly affected.
• acetylcholine receptors are lost following the binding of an antibody
  
  • receptors become cross-linked, endocytosis, and destruction within vessicles

Question 109

Training

Answer 109

• training for strength
  
  • myofibrils are added
  • fast muscle fibers
  • additional sarcomeres
• endurance training
  
  • increasing the ATP-generating machinery, mainly in the slow muscle fibers
• If a muscle is used less, the number of muscle fibers remains the same, but the individual muscle fibers decrease in size through the loss of myofibrils and sarcoplasmic reticulum. Such atrophy is usually most pronounced in the slow muscle fibers.

Question 110

Denervation.

Answer 110

• When a muscle fiber is denervated, the myofibrils and then muscle fiber itself degenerate over a period of months
• If another axon sprouts branches and begins to re-innervate the muscle fiber, however, the degeneration of the muscle fiber is reversed.
• type of muscle fiber that results depends on the specific efferent neuron that does the re-innervating, regardless of the original type of muscle fiber present.

Question 111

Jacksonian March

Answer 111

• Contractions begin first in muscles at the distal (farthest) ends of an extremity, such as in a finger. As the seizure continues, a progression of contractions moves proximally (from the end of the limb to the trunk)
• Shows the organization of the primary motor cortex

Question 112

Babinski Sign.

Answer 112

• ​the toes flare out to pain stimuli on sole
• Damage to the corticospinal tract

Question 113

Athetosis

Answer 113

• involuntary movements that are slow, writhing and wormlike
• degeneration of the basal ganglia here is usually the result of **cerebral palsy **
  
  • ​variety of motor abnormalities arising around the time birth
• An even more common symptom of cerebral palsy is spasticity.

Question 114

Encephalitis Lethargica

Answer 114

• flu infected brain
• lethargy and solmnolence
• developed symptoms similar to Parkinson’s disease, a consequence it seems of damage to the substantia nigra
• about a decade passed and then Parkinson’s-like symptoms began to show up again in some survivors
• ome of the surviving patients were “awakened” with varying success from their decades long immobility, using L-DOPA