Test 2 Flashcards
Glia
-Greek for glue
-Insulate, support and noursih neurons
-may even influence processing
-coookie portion of chocolate chip cookie
neurons
-Processes information
-Sense information
-Sense envrionemental changes
-Communicate changes to other neurons
-Command body response
-Chocolate chips of chocolate chip cookie
soma
-Greek for body
-AKA- cell body or perikaryon
-contains nucleus and many organelles
neurites
-anything coming off soma includes:
dendrites- receive info
axons- send info
nerve vs neuron
neruon: cells that sends and receives electrical signals
nerve: a group of fibers (axons) that carry information
The soma: cytosol
-watery fluid inside the cell, seperted from outside by neuronal membrane
The soma: Organelles
-membrane enclosed structures within the soma
-nucelus, endoplasmic reticulum, mitochondria
The soma: Cytoplasm
-Everything contained within the cell membrane
Cytoplasm= cytosol + organelles - nucleus
Neuronal membrane
-Barrier that encokeses cytoplasm and regulates membrane potential
-embeded within proteins that grant aess and regulate concentrations
-structure of membrane varies based on neuron regions
cytoskeleton of neuron
-“bones” of the neuron (providing rigidity)
-Not static- continually remodelling and in motion
-Three structures: microfilaments, neurofilaments, microtubules
infographic
a way to communicate important informaiton in a more engaging way
What causes Alzheimer’s disease
dominant theory has been build of plaque
-Amyloid hypothesis- plaque build uo on neuorns. Proteins not being cleared- build uo causes plaque that impacts brain communication
Although this is the dominant theory, plaque busting drugs have yet to show a lot of clincally significant improvements to symptoms
controversy of alzeimers drugs
speed of approval, yet to see lots of actual symtomatic imprvments. Drugs do in fact break down plaque- but seeing that it doesnt necesarly help QOL or symptoms
now seeing that some publications are making nots on early data
What else may be cuaseing alzheimers disease
Structure of axon is another major theroy
-Tau hypothesis
tangling of microtubiles may precede plawue formation
-variety of clinical trials with limited success
Tau and amyloid hypothesis together
likely these is a synergistic dance between amyloid and tau
-both occur together in patients with alzheimers disease
-inflammation and vasular dysfunction may initiate of accelerate the process
Axon length
Can range from less than 1mm to over 1m
not always a direct path- axon collaterals
Three areas of an axon
axon hillock (beginning)
axon proper (middle)
axon terminal (end)
note- synapse is the point of contact
axon thickness
humans- 1-25 nanometers in diameter
-generally, the thicker the axons, the faster the signal travels
How is the axon terminal different from the rest of the axon
-no microtubules in terminal
-has synaptic vesicles
-abundance of membrane proteins
-large number of mitochondria
axon synapse
-provides the contact site for transmission of signal (eg. electric-chemical-electric)
-Presynaptic (sends signal) vs postsynaptic (receives signal)
Dendrites
Greek for tree
-dentritic tree (all) with dentritic branches (individual)
-the “antennae” of neurons and covered in thousands of receptors- -roange dots on immunohistochemistry
-receptors ro receive neurotransmitters
classification of neurons based on number of neurites
-single neurite (unipolar)- sensory nerve with dorsal root gangilon
-two neurites (bipolar)- vestibulocochlear
-more than 2 neurites (multipolar)- many neurons in the body
classification of neurons based on dendritic and somatic morphology
-satate cells (star shaped)
-pyramidal cells (pyramid-shaped)
classification of neurons based on connections woth the cns
-primary sensory neruons
-motor neurons
-interneurons
classification of neurons based on axonal length
-golgi type I- long; go to other areas
-golgi type II- short; remain local
2 primary tpes of glia
astrocytes and myelinating glia
astrocytes
-most numerous glia in the brain
-fill spaces between neurons
-influence whether neurite grow/retract
-regulate chemical contect of extracellular space
myelinating glia
-insulate to faciliate transmission
-oligodendroglia (in CNS)
Canprovide myelin for multiple axons
-Schwann cells (in PNS)
Only provide myeling for one axon
Node of ranvier- region where axonal membrane is exposed
neural communication- electrical signal transmission by region
dendrites: initiate signal and pass towards axon
Axon hillock: action potential (AP) begins
Axon (axon proper): AP travels toawrds terminal
Axon terminal: receives AP and sends to other cells
Electrical signal is the change in electrical potential of the neuron (change in resting membrane potential)
Resting membrane potential
-difference between the inside (cytosol) and outside (extracellular membrane potential)
-typically -70mV
-Based on concentrations of NA+, K+, and Cl-
Membrane states: polarization
state wehn membrane potential is other than 0mV
(move away from zero)
Membrane states: depolarization
membrane becomes less polarized than at rest (moves to 0)
Membrane states: hyperpolarization
membrane becomes more polarized than at rest (even further away from zero)
Membrane states: repolarization
membrane returns to resting potential after a depolarization (away from zero)
2 kinds of membrane potential changes
graded potentials and action potentials
graded potentials
-serves as short distance signals
-initiated at dendrites (electrically, chemically, or mechincally) and passed towards axon (hillox)
action potentials
-serve as long-distance signals
-start at axon hillock quickly passed to axon termals
Properties of graded potentials (4)
- local (die quickly)
- summation- no refractpry period
- can vary in intensity
- can be excitatory-EPSP (depolarizing) or inhibitaroy-IPSP (hyperpolarizing)
summation (2 types)
spatial summation: generated simultaneously at different sites
temporal summation: generated at same site in rapid succession
no refractory period
graded potential to action potential
action potential occurs at the spike initation zone if graded potentials break threashold (-55mV)
States of the action potnetial
1.sufficient stimulus to break threashold
2. Rising phase: rapid depolarization (NA+ in)
3.Falling phase: membrane repolarization (K+ out)
4. Hyperpolarization below resting potential
-absolute refractory period (no stacking- unlike graded potentials)
-relative refractory period (due to hyperpolarized state)
5. resting membrane potential returns
key properties of the action potential
- all or none
-either produce an AP or not (singals are binary: on vs off, -1 vs 0) - firing rate conveys important information
-must code information in timing rather than magnitude of singal
Factors influencing conduction velocity
axon diameter
-bigger axons are faster- reduced resistance to flow
-survival pathways generally larger
myelin layers
-allow AP to jump across the axon (Nodes of ranvier)
-Schwann (PNS) vs Oligodendroglia (CNS)
continous conduction
-Unmelyinated fibers
– Action potential spreads along every portion of the membrane
saltatory conduction
-myelinated fibers
-Impulse jumps across breaks in myelin (node of Rnavier)
-~50x faster!
Multiple Sclerosis
-Autoimmune disorder characterized by the loss of myelin in the CNS (doesn’t impact the PNS)
-Decreased speed of nerve impusles (@regions below damage)
Multiple Sclerosis symotoms/ manifestation
-decreased speed of nerve impulses
-sensory- numbness, tingling and pain
-motor- loss of coordination in muscles
-Symptoms are highly variable within and between patients
Risk factors for MS
Age: Most diagnosed between 20-49 years of age
Genetics: Family history greatly greatly increases risk
other factors: infections, race, climate, vitamin d, diet, smoking
living in Canada” ~300 in every 100, 000 canadians
MS treatment
-No cure
-treat symtoms and progression with a variety of drugs (eg, mixed outcomes/side effects)
-Exercise can improve mobility, fatigue levels, and overall quality of life in MS patients (especially for mild-moderate patients…)
Slope walking and MS
where less myelin disruption was associated with greater intervention response
synapses
junctions between two neruons
-means by which one neuron interacts with another neuron
-first neuron: presynaptic neuron
-target cell: postsynaptic neruon
arrangements of synapses
axodendritic: axon-dendrite
axosomatic: axon to cell body
axoaxonix: axon to axon
dendrodendritic: dendrite to dendrite
electrical synapses
pre-synaptic neuron to postsynaptic neuron
-Action potential (axon) to graded potential (dendrite)
-Gap junction- very tight allowing ions flow from one neruon to other
chemical synapse: presynaptic neuron
conducts action potential toawrds synapse
chemical synapse: postsynaptic neruon
neruon whose signals are propagated away from the synapse
chemical synapse: synaptic vesicles
stores neurotransmitter (carries signal across a synpse)
chemical synapse: secretory granules
large vesicles that stores proteins
chemical synapse: synaptic cleft
space between the presynaptic and postsynaptic neurons (10x wider than gap junctions)
chemical synpase- steps
- action potential arrives at terminal
2.triggers release of neurotransmitter from synapstic vesicle
3.neurotransmitter migrates across synaptic celft - binds with receptor on postsynaptic neuron
- graded potential is triggered
- neurotransmitters quickly removed from synaptic cleft
The neuromusclar junction
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
generation of an EPSP
Na+ flos from synaptic cleft into the cell
depolarization- more likely to have an AP
generation of an IPSP
CL- flows from synpatic celft into the cell
hyperpolarization- less likely to have an AP
Do neurons just have on connection?
No- neurons typically undergo many EPSPs and IPSPs from different axon terminals
Some neurons have up to 200 000 terminals
What is required for a molecule to be considered a neurotransmitter
- Must be present within the presynaptic neuron
2.Must be released in response to a presynaptic depolarization - specific receptors must be present on the postsynaptic neuron
Neurotransmitters require mechnisms to..
-be synthesized in presynaptic neuron
-loaded into the synaptic vesicles
-spilled out into the synaptic cleft (ie exocitosis)
-Bind with the postsynaptic neuron and create a response
-Be removed (reuptake and degradation)
** All needs to happen in miliseconds
Neurotransmitters and synaptic drug interactions: possible drug interactions
-Altering the synthesis, transport, storage or release of a neurotransmitter
-modifying neurotransmitter interaction with the postsynaptic receptor
-influencing neurotransmitter reuptake or destruction
may also replace a neurotransmitter with a binding subsitute (agonist or antagonist)
Small mollecule neurotransmitters
synaptic vesicles
4 broad groupings:
Acetylcholine, amino acids, purines, amines
Peptide neurotransmitters
secretory granules
larger, slower
Acetylcholine
used at the NMJ and synthesized by all motor neurons
-cholinergic neurons- synthesize acetylecholines
Also plays a major role in a number of autonomic activities in the brain
acetylcholine enzymes: synthesis
choline acetyltransferase chAT
acetylcholine enzymes: breakdown
acetylcholinesterase AChE
Nerve gases (Sarin gas)
-inhibits acetylcholinesterase (AChE); ACh cannot be broken down from synaptic cleft (get constant ON state)
-can disrupt transmission on skeletal/heart muscle leading to death
Dopamine
Part of amines group - more specifcially catecholamines
dopaminergic neurons synthesize dopamine
how is dopamine synthesized (enzyme)
dopamine is synthesized from dopa with the enzyme dopa decarboxylase
dopamine enzyme: breakdown
Monoamine oxidase-B (MAO-B) enzymes breakdwon dopamine
what can happen if there is a lack of dopa
a lack of dopa can lead to the degradation and eventual death of some nerve cells int he brain (due to lack of signal because we can’t make dopamine)
-parkinson’s disease- tremors/ muscle rigidity
PD-Levadopa
-Supplements reduced levels of dopa
-crosses blood brain barrier
-most effective treatment, but can wear off and has side effects
PD- Dopamine agonists
-Mimics dopamine
-Good fisrt treatment but not as effective as levodopa (not great long term)
PD- MAO-B inhibitiors
-blocks the reuptake of dopamine
-allows the limited dopamine to stay in the cleft longer
Cocaine
blocks reuptake of neurotransmitter dopamine at presynaptic termials
methamphetamine
Not only blocks reuptake of dopamine, but increases its release as well
Meth and PD
-meth can lead to long term damage of dopaminergic neurons
-meth users are almost 2x as likely as non users to develop PD
-Still many other factors are presnt- but will PD rates continue to rise with rising rates of meth use?
