Topic Test 2 Flashcards
how does research get disseminated?
- published as journal articles
- published in peer-reviewed scientific journals
how is research disseminated when published as journal articles
describe background, methods, results, and conclusions
how is research disseminated when published in peer-reviewed scientific journals
- reviewed for technical and scientific quality by peers who are experts in the field
- goal is to reject articles that are based on flawed premises, poor study design, biased analysis or interpretations
- but the best journals reject a lot
top-tier journals reject a lot - how much do they reject?
- > 90%
- research not bad, just not ground-breaking
lower-end research journals are more accepting - what do they accept?
more incremental research
which process is the most important in research dissemination?
peer-review process
how do we get access to articles?
many require a subscription
- generally paid for by universities for students and researchers
Ongoing push for “open access” publications
- authors pay a fee so the articles are free to the public
why is open-access publication sometimes an issue?
some journals might forego quality control over money
how do we find articles?
databases and search engines
list the common structure of a journal article
abstract, introduction, methods, results, discussion, conclusion
describe the abstract
brief summary of the journal article
describe the introduction
what is the question?
describe the methods
how did you try to answer the question?
describe the results
what did you find?
describe the discussion
what does it mean?
describe the conclusion
take home message
what are the 6 questions you should ask when reading a scientific paper (ruel 3 of 10 smpl rules for reading a scientific paper)
1) what do they want to know?
2) What did they do?
3) Why did they do it that way?
4) What did the results show?
5) How did they interpret them?
6) What next?
list the reading tips (for papers) given in class
Will likely have to read it more than once
- give it a skim first (purpose, topic sentences, figures, conclusion)
Read critically
Be kind
list the components of reading critically (reading tips)
- remain open minded to the fact that your preciously held ideas may be wrong
- do not make the mistake of thinking that authors are always right
- keep in mind that writers of academic articles are trying to persuade you to agree with their ideas
treat critical reasing as a skill to develop through practice, think of:
- marking and looking up all vocab and oncepts that you’re unfamiliar with
- taking notes of the text’s main ideas and adding your own responsive comments
- talking to others about what you have read
- relating ideas from class
- thinking of summarizing/explaining what it means to a non-specialist - explain to friends/parents etc,
being able to succinctly summarize is key to showing you understand
the brain is the _ in the body
most complex organ
*it builds our entire worldly experience
what are the 2 types of cells in the nervous system
glia and neurons
describe glia
- greek for “glue
- insulate, support, and nourish neurons
- may even influence processing
*aka the cookie dough part of cookie
describe neurons
- process information
- sense environmental changes
- communicate changes to other neurons
- command body response
aka. chocolate in cookie
what are the 2 basic parts of a neuron?
soma and neurites
what is the soma? What does the soma consist of?
- greek for “body”
- aka cell body/perikaryon
- contains nucleus and many organelles
what do the neurites consist of?
dendrites: receive info
axons : send info
*anything thaat comes off the soma
name the difference between a neuron and nerve
neuron: cells that sends and receives electrical signals
nerve: a group of fibers that carry information (bundle of axons)
list the components of the soma
cytosol, organelles cytoplasm
describe the cytosol
watery fluid inside the cell, separated from outside by neuronal membrane
describe the organelles
- membrane enclosed structures within the soma
- nucleus, endoplasmic reticulum, mitochonria, etc.
describe the cytoplasm
- everything contained within the cell membrane
cytoplasm = cytosol+organelles-nucleus
name the other components in the neuron
neuronal membrane, cytoskeleton
describe the neuronal membrane
barrier that encloses cytoplasm and regulates membrane potential
- embedded with proteins that grant access and regulate concentrations
- structure of membrane varies based on neuron regions
describe the cytoskeleton
- bones of the neuron
- not static - continually remodeling and in motion
- 3 structures (microfilaments, neurofilaments, microtubules)
name the 3 stages of Alzheimer’s disease
- preclinical alzheimer’s
- mild cognitive impairment
- dementia
what has been the dominant theory on the cause of alzheimer’s disease?
amyloid plaques, proteins not cleared as they should be and they build up
- disrupt signalling/flow of info
- issues with how brain can manage protein breakdown
what solution did researchers come up with for alzheimers based on the amyloid hypothesis? What did they find?
- FDA approved drug that helps break down the plaque
- no noticeable symptomatic/clinical meaningful results even though plaque decreases
- others have since received more complete FDA approval
*none have received approval in Canada yet, but under review
what is the second major theory about the cause of Alzheimer’s?
- tau hypothesis
- structure of axon (itself that is breaking down)
- tangling of microtubules may precede plaque formation
- variety of clinical trials with limited success
Given the 2 theories on Alzheimer’s, which is a possible cause? What also plays a role?
- synergistic, amyloid and neurons/tau (not competing, working together to progress the disease)
- both occur together in patients
- inflammation (in CNS) and vascular dysfunction (bf less efficient) may initiate or accelerate the process
axons transfer information over distances - what is the range?
1mm to over 1m (sciatic nerve)
the axon has 3 areas - name them
axon hillock (beginning)
axon proper (middle)
axon terminal (end/transitioning between cell body and axon proper)
What is the point of contact between axon and another neuron?
synapse
axons don’t always have a direct path - what can we have instead?
axon collaterals
- 1 neuron won’t connect to another in 1-1 path
- millions of neurons connected in super complex ways
why does size matter in axons?
- the thicker the axons, the faster the signal travels
*humans have 1-25 hm in diameter (aka. length of your fingernail in a second)
How does the axon terminal differ from the rest of the axon?
- no microtubules in terminal
- has synaptic vesicles
- abundance of membrane proteins
- large number of mitochondria
what is the axon synapse?
- provides the contact site for transmission of signal (eg. electric-chemical-electric)
- presynaptic (sends signal) vs postsynaptic (receives signal)
*junction between the 2
what does “dendrites” mean in greek?
tree
describe dendrites
- dendritic tree (all) with dendritic branches (individual)
- the “antennae” of neurons and covered in thousands of receptors
- receptors to receive neurotransmitters
*all connections set up complex transmission of signals
how are neurons classified?
1) number of neurites
2) dendritic and somatic morphology
3) connections within the CNS
4) axonal length
how do we classify neurons based on the number of neurites?
- number of axons/dendrites branching off
- unipolar
- pseudounipolar
- bipolar
- multipolar
*based on number of neurites coming out from soma
what classifies a neuron as unipolar?
only 1 structure that extends from the soma
what classifies a neuron as bipolar?
one axon and one dendrite extending from soma
what classifies a neuron as multipolar?
one axon and multiple dendrites
*most common
what classifies a neuron as pseudounipolar?
- single structure that extends from the soma (like a unipolar cell), which later branches into two distinct structures (like a bipolar cell)
how do we classify neurons based on their dendritic and somatic morphology?
*how they are organized
- stellate cells (star-shaped, branching out in different directions)
- pyramidal cells (pyramid-shaped, less neurons, more organized)
how do we classify neurons based on their connections within the CNS?
- primary sensory neurons (afferent coming in), motor neurons (efferent coming out), interneurons
how do we classify neurons based on axonal length?
- golgi type 1 (long, go to other areas) *usually send from CNS down
- golgi type 2 (short, remain local)
What is the function of glia? What are the 2 primary types?
- support neuronal functions
astrocytes and myelinating glia
describe astrocytes
- most numerous glia in the brain
- fill spaces between neurons
- influence whether neurites grow/retract
- regulate chemical content of extracellular space (flow into/out)
Describe the different types of myelinating glia
oligodendroglia (in CNS)
- can provide myelin for multiple axons
Schwann cells (in PNS)
- only provide myelin for one axons
- also have node of ranvier
- region where axonal membrane is exposed (allows AP to move faster/jump between nodes)
what is the purpose of myelinating glia?
- insulate axons to facilitate transmission (inc. efficiency)
How do electrical signals pass through the neuron? (general overview)
- dendrites (initiate signal and pass towards axon)
- axon hillock (AP begins)
- axon proper (AP travels quickly towards terminal)
- axon terminal (receives AP and sends to other cells)
what “zones” correspond with dendrites/axon hillock/axon proper/axon terminal
input zone/dendrites
trigger zone/axon hillock
conducting zone/axon proper
output zone/axon terminals
what is the electrical signal in neuronal communication?
change in the electrical potential of the neuron (change in resting membrane potential)
describe the resting membrane potential
- difference between the inside (cytosol) and outside (extracellular fluid)
- typically -70 mV
- based on concentrations of Na+, K+, Cl-
list the membrane states
polarization, depolarization, repolarization, hyperpolarization
describe polarization
- state when membrane potential is other than 0mv
*moving away from 0, more negative
describe depolarization
membrane becomes less polarized than at rest
*moving towards 0, more positive
describe repolarization
membrane returns to resting potential after a depolarization
*coming back to membrane potential, moving away from 0
describe hyperpolarization
- membrane becomes more polarized than at rest
*moving even farther away from 0 pastd resting potential, more negative
downward inflection on membrane potential graph =
increase in potential (harder to get to AP threshold)
upward inflection on membrane potential graph =
decrease in potential (easier to get to AP threshold)
what are the 2 kinds of membrane potential changes?
- graded potentials
- action potentials
describe graded potentials
- serve as short-distance signals
- intitated at dendrites (electrically, chemically, or mechanically) and passed towards axon
*eventually turn into AP - neuron’s job to decide which signals become AP
*local small changes in mem. potential
*need to be strong/summate
list the 4 graded potential properties
1) local - die quickly
2) summation
3) can vary in intensity (can have really strong GPs that create APs
4) can be excitatory (depolarizing) or inhibitory (hyperpolarizing)
describe summation as a graded potential property
spatial summation: generated simultaneously at different sites
temporal summation: generated at same site in rapid succession
*no refractory period (can stack them up to get AP)
describe the property where GPs can be excitatory/inhibitory
- many types of graded potentials
- EPSP (excitatory postsynaptic potential), depolarizing towards threshold)
- IPSP (inhibitory postsynaptic potential/make it harder for AP to exist)
Action potential occurs at _ if _
the spike initiation zone
- if graded potentials break threshold (-55mV)
list the 5 stages of the action potential
1) sufficient stimulus to break threshold
2) Rising phase: rapid depolarization (NA+ in)
3) Falling phase: membrane repolarization (K out)
4) Hyperpolarization: below resting potential (absolute refractory period/relative refractory period)
5) Resting membrane potential returns
Action potentials can’t be stacked… describe the absolute/relative refractory periods that determine this rule
absolute refractory period
- no other APs will happen
relative refractory period
- we are hyperpolarized so it will be hard to deviate a signal past the threshold cause way below -70, still possible though
name the 2 key properties of the action potential
1) All-or-none principle
2) Firing rate conveys important informationn
describe the all-or-none principle
- either reach threshold and produce AP or no AP is produced
- signals are binary: ON vs OFF (1 vs 0)
describe how AP firing rate conveys important information
- must code information in timing rather than magnitude of signal
(if input (aka. gp) is high enough/frequent enough, APs can constantly be initiated as soon as we leave the absolute refractory period)
list the factors influencing conduction velocity
- axonal diameter
- myelin layers
describe how axonal diameter influences conduction velocity
- bigger axons are faster -reduced resistance to flow
- survival pathways generally larger
describe how myelin layers influence conduction velocity
- allow APs to jump across the axon (nodes of ranvier)
- schwann (PNS) vs. oligodendroglia (CNS)
*(if we don’t have myelin, ap has to go through gated ion channels at every point, would be slower)
what are the different types of conduction? (aka other names for myelinated vs. unmyelinated
- continuous conduction
- saltatory conduction
describe continuous conduction
- action potential spreads along every portion of the membrane
describe saltatory conduction
- impulse jumps across breaks in myelin (nodes of ranvier)
- ~50x faster
What is multiple sclerosis?
autoimmune disorder characterized by the loss of myelin in the CNS (spinal cord/brain)
- decreased speed of nerve impulses
what exactly happens to the myelin in MS?
(attacks myelin sheath, inflamed/damaged = nerve becomes exposed)
- affected areas depend on area of damage
describe the symptoms of multiple sclerosis
- decreased speed of nerve impulses
- sensory: numbness, tingling and pain
- motor - loss of coordination in muscles
- symptoms are highly variable within and between patients
name the symptoms on the MS in america infographic in order from most to least common
- numbness, tingling
- walking difficulty
- vision problems
- fatigue
- weakness
- dizzyness
- muscle spasms
- pain
- depression
- cognitive dysfunction
- bladder dysfunction
name the MS risk factors
- age: most diagnosed between 20-49 years of age
- genetics: family history greatly increases risk
- other factors: infections, race, clinate, vitamin D, diet, smoking
- living in canada?( vit d deficiency could increase risk if you have the genetic predisposition)
describe the treatment of MS
- no cure
- treat symptoms and progression with a variety of drugs (eg. mixer outcomes/side-effects)
*not reversing/modifying the disease - exercise can improve mobility, fatigue levels, and overall quality of life in MS patients (somewhat effective in milk-moderate but maybe not after)
in the study determining the relationship between myelin status and functional improvement following walking intervention (slope walking), what responses were seen?
- “change in functional mobility”
- the people who have less myelin disruption have a greater response to this intervention (when the myelin is significantly impacted, hard to improve things)
*the earlier we diagnose, the earlier we can intervene
name the stages of MS based on the infographic shown in class. Which stages did Kobsar want to focus on when doing the lokomat/zero g study?
0- no disability
1 - minimal symptoms
2 - minimal disability
3 - moderate disability
4 - significant disability
5 - disability limits daily tasks
6 - walking aid is required
7 - uses wheelchair exclusively
8 - needs assistance with wheelchair
9 - unable to leave bed
10 - death from MS
*want stages 4-7
when the membrane potential of a neuron becomes less polarized than at rest it is called
depolarization
describe synapses
- junction between 2 neurons
- means by which one neuron interacts with another neuron
*first neuron - presynaptic neuron
*target cell - postsynaptic neuron
(not on slide but we have lots of synapses in a path)
synapses come in a variety of arrangements - name them
- axodendritic: axon to dendrite (most simplistic)
- axosomatic: axon to cell body
- axoaxonic: axon to axon
- dendrodendritic: dendrite to dendrite
describe electrical synapses
- presynaptic neuron to postsynaptic neuron
- action potential (axon) to graded potential (dendrite)
- gap junction: very tight allowing ion flow from one neuron to other (allows it to jump)
Once an action potential jumps to postsynaptic neuron, it becomes _
a graded potential
describe the structures involved in chemical synapses
- Presynaptic neuron
- postsynaptic neuron
- synaptic vesicles
- secretory granules
- synaptic cleft
compare what a pre and postsynaptic neuron does in a chemical synapse
Presynaptic neuron: conducts action potential towards synapse
Postsynaptic neuron: neuron whose signals are propogated away from the synapse
describe what these structures do in a chemical synapse:
a) synaptic vesicles
b) secretory granules
c) synaptic cleft
Synaptic vesicles - stores neurotransmitter (carries signal across a synapse)
Secretory granules - large vesicles that stores proteins
Synaptic cleft - space between the presynaptic and postsynaptic neurons (10x wider than a gap junction)
list the steps in a chemical synapse
1) AP arrives at terminal
2) Triggers release of neurotransmitter from synaptic vesicle
3) neurotransmitter migrates across synaptic cleft
4) Binds with receptors on postsynaptic neuron
5) GP is triggered
6) Neurotransmitters quickly removed from synaptic clefrt
describe the neuromuscular junction (NMJ)
synaptic junction onto muscle
- one of the largest synapse in the body
- fast and reliable
- large number of active zones aligned with folds in the motor end-plate
- much easier to study! (bigger and easier to see)
how are EPSPs generated?
- positive ions sent into postsynaptic dendrite
- get depolarization = excitatory signal = pushing closer to AP in subsequent neuron
how are IPSPs generated?
- sending in negative ions into postsynaptic neuron, get hyperpolarization/pushing farther away from AP
what are IPSPs and EPSPs?
graded potentials that are either depolarizing the neuron or hyperpolarizing the neuron
real neurons typically undergo many _
EPSPs and IPSPs from different axon terminals
*neurons have 1000s of connections and a lot of these are happening at once
some neurons have up to _ terminals
200,000
*neurons have to figure out if they should send AP based on inpu (temporal summation in quick succession/spatial summation with multiple adding)
what is required for a molecule to be considered a neurotransmitter?
1) must be present within the presynaptic neuron
2) must be released in response to a presynaptic depolarization
3) specific receptors must be present on the postsynaptic neuron
neurotransmitters require mechanisms to…
- be synthesized in the presynaptic neuron
- loaded into the synaptic vesicles
- spilled out into the synaptic cleft (ie. exocytosis)
- bind with the postsynaptic neuron and create a response
- be removed (reuptake and degradation)
*all needs to happen in milliseconds
what are possible drug actions (neurotransmitters and synaptic drug interactions)
- altering the synthesis, transport, storage, or release of a neurotransmitter
- modifying neurotransmitter interaction with the postsynaptic receptor
- influencing neurotransmitter reuptake or destruction
- replacing a neurotransmitter with a binding substitute (agonist/antagonist)
list and describe the different types of neurotransmitters
Small molecule neurotransmitters
- (go into) synaptic vesicles
- 4 broad groupings (acetylcholine, amino acids, purines, amines)
Peptide neurotransmitters
- secretory granules
- larger, slower
describe acetylcholine
- used at the NMJ and synthesized by all motor neurons (“ergic” in cholinergic means neuron synthesizes)
- also plays a major role in a number of autonomic activities in the brain
in terms of acetylcholine, enzymes are required to:
- synthesize (choline acetyltransferase - ChAT)
- breakdown (acetylcholinesterase - AChE)
- Nerve gases (Sarin gas) inhibit acetylholinesterase (AChE); ACh cannot be removed from synaptic cleft
- can disrupt transmission in skeletal/heart muscle leading to death
how does ACH connect to movement?
really important for movement, used at NMJ (where nerve synapses onto muscle to cause contraction)
describe how ACH is used in steps
- create ach (with ChAT) and package up to be released
- AP comes down to presynaptic, tells ACh to be released, helps transmit signal
- when ACh is done binding on postsynaptic cell, need to break it down (acetylcholinesterase)
- bring back parts to start process over
describe dopamine
- part of the amines group (specifically catecolamines)
- dopaminergic neurons
- synthesized from dopa with the enzyme dopa decarboxylase
- monoamine oxidase-B (MAO-B) enzymes breakdown dopamine
what building block and enzyme is dopamine synthesized with?
dopa with the enzyme dopa decarboxylase
what enzyme breaks down dopamine?
MAO-B (monoamine oxidase-B)
*allows the cycle to start all over again
A lack of dopa can lead to _
the degradation and eventual death of some nerve cells in the brain
- parkinson’s disease (tremors/muscle rigidity/freezing of gait)
*issue comes from breakdown of dopaminergic neurons
list the different treatments for parkinson’s disease (drug specific)
levodopa, dopamine agonists, MAO-B inhibitors
describe the function of Levodopa
- supplements reduced levels of dopa
- crosses blood brain barrier (since being synthesized by enzymes, more natural option)
- most effective treatment but…
- can wear off and has side effects
describe the function of dopamine agonists
- mimics dopamine (aka agonist/synthetic dopamine that binds to dopamine receptors)
- good first treatment, but not as effective as Levodopa (not longterm)
describe how MAO-B inhibitors function
- block the reuptake of dopamine (because of preventing breakdown)
*this allows it to stay in cleft a little longer
which Parkinson’s disease drug treatment is the best?
Levodopa but pros and cons with each one, likely best effect when all working together at the same time/in some combination
how does cocaine interact with the synapse?
- blocks reuptake of neurotransmitter dopamine at presynaptic terminals
how does methamphetammine interact with the synapse?
not only blocks reuptake of dopamine, but increases its release as well
how does methamphetamine interact with parkinson’s disease?
- can lead to long-term damage of dopaminergic neurons
- methamphetamine users are almost twice as likely as non-users to develop PD (goes from ~1/500 to 2/500 though)
*still many other factors (genetics, age, sex, other environmental)
-could pd rates continue to rise with increased meth use?
