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Know what the blood brain barrier (BBB) is.
The BBB is the barrier between the circulatory system and the brain. Discovered by Paul Ehrlich, around 1900. Brain needs BBB because it has a weak immune system. BBB minimizes the loss of neurons (more neurons cannot be made)
Know what can pass through the blood brain barrier without the use of energy and know what substances need to be to be actively (using energy) moved across the blood brain barrier using transport molecules.
without the use of energy: O2, CO2, & small uncharged fat soluble molecules
actively moved (with energy): glucose and some large amino acids cross via energy dependent active transport
Know what the circumventricular organ is and know why we need to have weaknesses in some parts of the blood brain barrier.
Circumventricular organs are areas where the BBB is weakened.
We need leaky regions in some parts of the brain so that the brain can monitor our blood contents to regulate physiology and tell us if we need to vomit. The pineal and pituitary glands secrete hormones that get into the bloodstream thanks to the leaks in the BBB.
Know why heroin is more potent than morphine (this has to do with blood brain barrier permeability).
Heroin is 3x more potent than morphine because it is fat soluble, so it goes straight through the blood brain barrier.
Know what the primary fuel (energy source) for neurons is.
Glucose in a metabolic pathway with O2
Know the cause and symptoms of Korsakoff's syndrome.
Cause: due to lack of thiamine (this kills neurons in the brain)
Symptoms: can't remember things and can't create new memories
Know what the cell membrane is and what it is composed of.
The site where most processes involved in neuronal preservation and functioning are triggered. Maintains electrical gradient necessary for signaling. Covers entire neuron. Selectively permeable.
composed of 2 layers of fat and phosphate molecules (phospholipid bilayer)
Know what can and cannot pass through the cell membrane without the use of protein ion channels and pumps.
O2 & CO2 go right through
small uncharged fat soluble molecules - water, glycerol, urea, ethanol - go right through (not as quickly as gasses though)
Charged molecules cannot go through - Na, K, Chloride (Cl), Calcium (Ca), Hydrogen (H)
Ion channels and pumps are ________.
proteins
Know the difference between ion channels and pumps, and know the difference between passive, voltage-gated, and ligand (transmitter)-gated ion channels.
Pumps use energy to move ions, while channels do not.
Passive ion channels are always open.
Voltage-gated ion channels open when the membrane potential changes to a specific voltage, closed at some voltages and opened at other voltages.
Ligand-gated ion channels open when a neurotransmitter binds to the protein
Know the different ion channels and pumps (and their characteristics) that play a role in the resting potential and action potential of neurons.
Sodium-Potassium Pump: moves Sodium out and Potassium in. ALWAYS RUNNING!
State of ion channels at resting potential:
K+ passive channels are always open.,
Na+ channels are not
Results in a slow steady leak of K+ out of the neuron down its concentration gradient
Know where NA+, K+, and A- ions are more concentrated (inside or outside of the neuron) when the neuron is at rest.
Na+ is more concentrated outside of the neuron.
K+ and A- are more concentrated inside of the neuron.
Know what the resting potential is and be able to explain why it is important that neurons have a resting potential.
The resting potential is the -55 to -70 mv difference in charge when the neuron is not sending a message.
It is important because it is needed in order for an action potential to be produced. A stored up difference in charge across the membrane makes an action potential possible.
Be able to explain how concentration forces effect the distribution and movement of ions across the neuronal cell membrane.
Ions move from an area of high concentration to an area of low concentration.
Diffusion (concentration) forces work to equalize the concentration of ions across the membrane
Be able to explain how electrical forces effect the distribution and movement of ions across the neuronal cell membrane.
Electrical gradient is the gradient that develops because of the difference in charge across the membrane. Opposite charges ATTRACT and Like charges REPEL.
Be able to explain which ions are moved across the membrane (and in which direction) with each cycle of the sodium-potassium pump.
With each cycle, 3 sodium ions exit the cell and 2 potassium enter.
Be able to describe the experiments using squid giant axons that were conducted to figure out how an action potential could be produced using electrical stimulation of a neuron/axon.
Hodgkin & Huxley experimentally studied action potentials. They used squid because their axons are bigger than typical axons, making electrical stimulation of the axon much easier. They placed electrodes in the middle of the axon in order to artificially start an action potential. Two potentials occur. One will roll to the soma where it will die, and the other will travel toward the nerve terminal.
Hyperpolarizing stimulation:
making the inside of the axon more negative than it was at rest
Depolarizing stimulation:
making the inside of the axon more positive than it was at rest
Graded/local potentials:
- can sum together local potentials
- caused by opening of transmitter(ligand)-gated channels only
vs. Action potentials:
- cannot be summed together
- caused by opening of voltage-gated channels
- cannot be graded (proportional)
- all or none
Know what the threshold potential is, and what happens when you depolarize a neuron and reach this potential.
Threshold Potential: the level to which a membrane potential must be depolarized to in order to start an action potential
when you depolarize a neuron and reach this potential, an action potential occurs.
Be able to define Action Potential.
brief depolarization of the axon that provides the basis for conduction of information along the axon
Be able to explain the chain of events that occurs when an action potential is electrically stimulated that cause the upswing (depolarization phase) and the downswing (repolarization phase) of the action potential.
The upsweep is due to sodium entry. Once the threshold potential is hit, voltage-gated sodium channels open quickly. Voltage-gated potassium channels begin to open, slowly. When voltage-gated sodium channels open, sodium will go in because it is attracted to the negativity. Sodium changes shape before going into the refractory period. At the peak of the action potential, there is a lot of permeability, sodium (and potassium) leaves and the action potential returns to the resting potential.
Know what tetrodotoxin (TTX), and local anesthetics like Novocaine do to stop action potentials from occurring.
Block voltage-gated channels
Know what the absolute refractory period is, and why it occurs.
The absolute refractory period is a period of time where it is impossible for the cell to send more action potentials. This is due to the gating mechanism of the voltage-gated sodium channels. After a period of being open, the channels close and are inactivated.
Know what the relative refractory period is, and why it occurs.
The relative refractory period is the period of time (2-4 ms) during which a second action potential can be initiated, but initiation will require a greater stimulus than before. It is caused by the opening of voltage-gated sodium channels (hyperpolarized)
Be able to explain how the intensity of a stimulus can be coded using a single neuron, and larger populations of neurons.
- Stimulus intensity coded as a change in frequency of action potentials along a given axon
- May also recruit more neurons as intensity increases
Be able to explain how an action potential travels down an unmyelinated axon without getting smaller.
In an unmyelinated axon, an action potential is constantly regenerated between the nodes of Ranvier as it travels. The signal does not decay over distance, but it takes time for all those ions to move in and out of the axon
Be able to explain how an action potential travels down a myelinated axon without getting smaller.
The action potential jumps between the nodes of Ranvier through saltatory conduction. Signals travel passively under myelin until nodes where ion channels are found and the action potential is regenerated.
Know what the myelin sheath is, and how it increases action potential speed by increasing external membrane resistance to ion flow.
Myelin Sheath is a sheath of fatty tissue that protects nerve cells.
Myelin increases action potential speed by increasing external membrane resistance.
Know the approximate degree to which myelin increases the speed of conduction on an axon.
Myelin increases the speed of conduction on an axon by 10X.
Be able to explain the importance of the nodes of Ranvier.
The nodes of Ranvier allow for the electrical signal to travel down the axon.
Know why squid (and other invertebrates) have a pair of giant axons in their nervous system. Why has the squid evolved giant axons, and what does the large axon diameter do for the squid.
Squid (and other invertebrates) have a pair of giant axons in their nervous systems' so they can escape danger quickly. The large axon diameter allows for action potentials to travel faster. The thicker the axon, the less internal resistance.
Know what multiple sclerosis is and know the meaning (translation) of the name multiple sclerosis.
- Autoimmune disorder - immune system attacks myelin sheath. myelin is lost in multiple areas, leaving scar tissue called sclerosis
- Greek for "many scars"
Be familiar with the common symptoms of multiple sclerosis.
Symptoms vary depending on where the myelination loss occurs in the brain. Symptoms vary in severity from mild tingling sensations to severe paralysis. Symptoms may be sensory, motor, and cognitive or some combination.
Most common: (don't have to memorize, provided to show that symptoms vary greatly, sensory input & motor control problems)
Bladder dysfunction, bowel dysfunction, cognitive dysfunction (memory attention problem solving), dizziness and vertigo, depression and other emotional changes, fatigue, difficulty walking (balance and coordination), numbness or "pins and needles," pain, sexual dysfunction, spasticity, vision problems
Know the most common course of treatment for multiple sclerosis.
Most often immunosuppressant drugs:
-- Interferons (B-interferon) proteins that regulate the immune system: Avonex, Betaseron, Copaxone, Rebif, Novantrone
Know what an IPSP is and how one is produced.
An inhibitory postsynaptic potential is a temporary hyperpolarization of the postsynaptic membrane caused by the flow negatively charged ions into the postsynaptic cell. An IPSP is produced when an inhibitory presynaptic cell, connected to the dendrite, fires an action potential
Know what an EPSP is and how one is produced.
An excitatory postsynaptic potential is a temporary depolarization. An EPSP occurs when sodium channels open in response to a stimulus.
Temporal summation:
repeated stimuli occurring within a brief time (at the same location on a neuron) can produce an action potential when a single stimulus is too weak.
- sawtooth pattern
Spatial summation:
several synaptic inputs originating from separate locations can also have a cumulative effect on a neuron and cause an action potential when single input would not
Be able to explain what occurs when a neuron receives many, many, IPSPs and EPSPs to determine whether the receiving (postsynaptic) neuron will generate an action potential.
When a neuron receives many EPSPs in a certain period of time, they can be stacked in order to reach the threshold potential.
IPSPs keep the neuron from generating an action potential by hyperpolarizing the neuron, pushing it away from the threshold potential
Who discovered the blood brain barrier? What role do astrocytes play in the formation of the blood brain barrier? Why is there a need for weakened (leaky) regions in the blood brain barrier?
Paul Ehrlich discovered the BBB. Astrocytes form the basis of the BBB. Astrocyte foot processes secrete chemicals that cause tightening, so things don't leak through the BBB. There is a need for leaky regions in the BBB so that the brain can monitor blood contents to regulate physiology and tell the body if it needs to vomit. Also, the pineal and pituitary glands secrete hormones that must get into the bloodstream. Leaks in the BBB allow these hormones to do so.
You provide intermittent, low-level, depolarizing stimulation to the axon, but instead of getting an action potential, all you get are small, short-lived changes in the potential across the axonal membrane. Be able to explain what these changes in potential are called, and be able to explain why you have failed to produce an action potential with the stimulation you have provided?
You then provide additional depolarizing stimulation to the giant squid giant axon and an action potential is produced. Explain how the actions of ion channels and the movement of ions across the axonal membrane cause the depolarization phase (the upsweep) of the action potential and the subsequent return to the resting potential.
Graded potentials are small short-lived changes in the potential across the axonal membrane. I have failed to produce an action potential with the stimulation I provided because I need to shorten the amount of time between each stimulation.
The upsweep is due to sodium entry. Once the threshold potential is hit, voltage-gated sodium channels open quickly. Voltage-gated potassium channels begin to open, slowly. When voltage-gated sodium channels open, sodium will go in because it is attracted to the negativity. Sodium changes shape before going into the refractory period. At the peak of the action potential, there is a lot of permeability, sodium (and potassium) leaves and the action potential returns to the resting potential.
When a neuron receives natural stimulation (from other neurons), why do action potentials first form at the axon hillock rather than in the dendrites or soma of a neuron?
Action potentials first form at the axon hillock because this is the first place in the neuron where voltage-gated sodium channels can be opened.
Why does the size of an action potential remain constant as it travels down an unmyelinated axon?
The size of an action potential remains constant as it travels down an unmyelinated axon by opening voltage-gated channels along the axon.
How would the shape of your action potential change, if you were to treat the axon with a chemical that selectively blocked voltage-gated K+ channels without altering the activity of any other channels? Please explain your answer. You will need to think this through to answer it.
It would take tens of milliseconds for the membrane to repolarize and transmit another action potential. This would create a prolonged shape.
If you place your stimulating electrode inside of a long axon midway between the soma of the neuron and the axon terminal (end foot), and provide stimulation sufficient to cause an action potential, in what direction will the action potential travel?
Hint: if you start the action potential in the middle of an axon, none of the tissue around your stimulating electrode is in a refractory state.
The action potential will travel in both directions.