Topic 2: Neuroscience Foundations Flashcards
Glia
- Glue
- Insulate, support, and nourish neurons
- support neuronal function
Jobs of Neurons
- Process information
- Sense environmental changes
- Communicate changes to other neurons
- Command body response
Parts of a neuron
- Soma
- Neurites
The Soma
- cell body
- Contains nucleus and many organelles, cytosol and cytoplasm
Neurties
- Dendrites: receive information
- Axons: send information
-More concerned with connections rather than the inner workings/physiology of the neuron
Neuron vs Nerve
Neuron: Cells that sends and receives electrical signals
Nerve: a group of fibers that carry information
Cytosol of neuron
water fluid inside the cell, separate from outside by neuronal membrane
Organelles of neuron
- Membrance enclosed structures within the soma
- Nucleus, endoplasmic reticulum, mitochondria
Cytoplasm of neuron
Everything contained within the cell membrane
- Cytoplasm = cytosol + organelles - nucleus
Neuronal membrane of neuron
- Barrier that encloses cytoplasm and regulates membrance potential
- Embedded with proteins that grant access and regulate concentrations
- Structure of membrane varies based on neuron regions
Cytoskeleton of neuron
- “bones” of neuron
- not static (continually remodeling and in motion)
- made of:
MICROFILAMENTS: weave to form strict
NEUROFILAMENTS: weave to form structure
MICROTUBULES: run longitudinally
Inforgraphic
a wat to communicate important information in a more engaging way
Three stages of Alzheimer’s disease
- Preclinical: subtle changes in brain, biomarkers in the cerebrospinal fluid and blood. the disease is often undetectable in this stage, except in research setting.
- Mild Cognitive impairment: changes in memory and other cognitive functions, like problem-solving and changes in judgement, but not enough to affect daily function
- Dementia: more significant changes memory, cognitive and physical abilities. trouble completing simple everyday tasks. Changes in mood, behaviour and personality.
What causes Alzheimer’s Disease?
AMYLOID HYPOTHESIS
- Built up coagulated plaque made of proteins disturbs neural signals impacting brain function
- Aducanumab seen to reduce plaque in brain but doesn’t produce positive patient outcomes
TAU HYPOTHESIS
- tangling of microtubules may precede plaque formation (neurofibrillary tangle) causing a decrease in transmission
SYNTERGIST DANCE BETWEEN AMYLOID AND TAU
- inflammation and vascular dysfunction may initiate or accelerate the process
Axon
- Transfer information over distances (can range form less than 1mm to 1m)
- Made up of the hillock (beginning), proper (middle) and terminal (end)
- Not always a direct path (axon collaterals)
- Size does matter (1 - 25 nanometers in diameter, thick axons are faster)
Terminal of Axon
- no microtubules in terminal
- has synaptic vesicles
-abundance of membrane proteins - large number of mitochondria
Synapse
- Provides the contact site for transmission of signal
- Presynaptic - sends signal
- Postsynaptic - receives signal
Dendrites
- dendritic tree (all) with dendritic branches (individual)
- the antennae of neurons and covered in thousands of receptors
- receptors to receive neurotransmitters
What are the 4 ways to classify neurons
- Classification based on number of neurites
- Classification based on dendritic and somatic morphology
- Classification by connections within the CNS
- Classification based on axonal length
How can neurons be classified based on number of neurites
- Unipolar or pseudo-unipolar (single neurite)
- Bipolar (two neurites
- Multipolar (more than 2 neurites)
How can neurons be classified based on dendritic and somatic morphology
- Stellate cells (star shapes)
- lot of local connections - Pyramidal cells (pyramid shape)
- covers more distance
How can neurons be classified based on connections within the CNS
- Primary sensory neurons
- Motor neurons
- Interneurons
How can neurons be classified based on axonal length
- Golgi type I (long and go to other areas)
- Golgi type II (short and remain local)
Types of Glia
- Astrocytes
- Most numerous glia in the brain
- Fill space between neurons
- Influence whether neurite grow/retract
- Regulate chemical context of extracellular space - Myelinating glia
- Insulate axons to facilitate transmission
- Oligodendroglia in CNS (can provide myelin for multiple axons)
- Schwann cells in PNS (only provide myelin for one axon)
Path of electrical signals in neural communication
- Input Zone (Dendrites)
- Initiate signal and pass towards axon - Trigger Zone (Axon Hillock)
- AP begins - Conducting Zone (Axon proper)
- AP travels quickly towards terminal - Output zone (axon terminal)
- Receives AP and sends to other cells
What is the electrical signal that is transmitted in neurons
a change in the electrical potential of the neuron
Resting membrane potential
- Difference between the inside (cytosol) and outside (extracellular fluid)
- Typically -70mV
- based on concentrations of Na+, K+ and Cl-
Def: Polarization
State when membrane potential is other than 0mV
Def: Depolarized
Membrane becomes less polarized than at rest
Def: Repolarization
Membrane returns to resting potential after a depolarization
Def: Hyperpolarization
Membrane becomes more polarized than at rest
What are the two kinds of membrane potential changes
- Graded potentials
- Serve as short distance signals
- initiated at dendrites and passed towards axon - Action Potentials
- Serve as long-distance signals
- Start at axon hillock and are quickly passed to axon terminal
4 properties of graded potential
- Local - die quickly
- Summation
- Spatial summation: generated simultaneously at different sites
- Temporal summation: generated at same site in rapid succession
-no refractory period - Can vary in intensity
- Can be excitatory (EPSP) or inhibitory (IPSP)
how does a graded potential become an action potential?
AP occurs if graded potentials break threshold (-55mV) at spike initiation zone (axon hillock)
Stages of the AP
- Sufficient stimulus to break threshold
- Rising phase: rapid depolarization (Na+ in)
- Falling phase: rapid repolarization (K+ out)
- Hyperpolarization (relative refractory period)
- Resting membrane potential returns
2 properties of the action potential
- All or none principle
- Either reach threshold and produce AP or no AP is produced - Firing rate conveys important info
- Must code info in timing rather than magnitude of signal
Factors influencing conduction velocity
- Axonal diameter
- bigger axons are faster
- survival pathways generally larger - Number of voltage-gated channels
- fewer openings force current down axon - Myelin layers
- Contiguous conduction (unmyelinated): AP spreads along every portion of the membrane
-Saltatory conduction (myelinated): Impulse jumps across nodes of Ranvier (about 50x faster)
What is Multiple Sclerosis?
Autoimmune disorder characterized by the loss of myelin in the CNS
What are 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
What are the risk factors for MS
- Age: usually occurs in adults (18-35 most common)
- Sex: Women 2x more likely
- Genetics: Family history greatly increases risk
- Other factors: infections, race, climate vitamin d, diet, smoking
MS treatment
- No cure
- Treat symptoms and progression with a variety of drugs
- Exercise can improve mobility, fatigue levels and overall quality of life - especially for mild-moderate patients
Def: synapses
Junction between two neurons
- means by which one neuron interacts with another neuron
Synapse arrangements
- Axodendritic: axon to dendrite
- Axosomatic: axon to cell body
- Axoaxonic: axon to axon
- Dendrodendritic: dendrite to dendrite
Electrical Synapses
- Still has presynaptic and postsynaptic neuron and AP to GP
- Connected by gap junction: very tight connection allowing ions to flow from one neuron to another
Components of Chemical Synapse
PRESYNAPTIC NERUON - conducts action potential toward synapse
POSTSYNAPTIC NEURON - neuron whose signals are propagated away from the synapse
SYNAPTIC VESICLES - stores neurotransmitter
SECRETORY GRANULES - large vesicles that stores proteins
SYNAPTIC CLEFT - space between the presynaptic and postsynaptic neurons
Steps of a chemical synapse
- AP arrives at terminal
- Triggers release of neurotransmitter from synaptic vesicle
- Neurotransmitter migrates across synaptic cleft
- Binds with receptors on postsynaptic neuron
- Graded potential is triggered
- Neurotransmitters quickly removed from synaptic cleft
Neuromuscular 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
Generation of EPSPs vs IPSPs
EPSP: Na+ enters cell
IPSP: Cl- enters cell
- neurons undergo many EPSPs and IPSPs from different axon terminals
What is required for a molecule to be considered a neurotransmitter
- Must be present within the presynaptic neuron
- Must be released in response to a presynaptic depolarization
- 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
-bind with the postsynaptic neuron and create a response - be removed
Possible drug actions
- 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
Small molecule neurotransmitters
- Synaptic vesicles
- 4 broad groupings: ACh, amino acids, purines, amines
Peptide neurotransmitters
- Secretory granules
- larger, slower
Acetylcholine
- Used at NMJ and synthesized by all motor neurons
- plays major role in a number of autonomic activities in the brain
- made by cholinergic neurons
Enzymes involved with ACh
Synthesis: Choline acetyltransferase (ChAT)
Breakdown: acetylcholinesterase (AChE)
- Nerve gases (sarin gas) inhibit AChE
- can disrupt transmission in skeletal/heart muscle leading to death
Dopamine
- Part of the amines group (catecholamines)
- Made by dopaminergic neurons
- Synthesized from dopa with the enzyme dopa decarboxylase
- Monoamine oxidase-B (MAO-B) enzymes breakdown dopamine
-lack of dopa can lead to the degradation and eventual death of some nerve cells in the brain (parkinson’s disease - tremors/muscle rigidity)
Medication used for Parkinson’s disease
Levadopa
- Supplements reduced levels of dopa
- crosses blood brain barrier
- most effective treatment but can wear off and has side effects
Dopamine agonists
- mimics dopamine
- good first treatment, not as effective as levadopa
MAO-B inhibitors
-block reuptake of dopamine
Cocaine interactions with dopamine
Blocks reuptake of neurotransmitter dopamine at presynaptic terminals
Methamphetamine interactions with dopamine and implications
Not only blocks reuptake of dopamine, but increases its release as well
- can lead to long-term damage of dopaminergic neurons
- meth users are almost 2x as likely to develop PD
