Chapter 4 Flashcards
Parkinson’s Disease Case
-Referred to as a lizard
-Name Robert Garcia d’Orta
-Symptoms: Tremor, hands shake worse
Tremor at rest
The hands shake worse when they are doing nothing at all
Symtoms of Parkinson’s Disease
-Tremors
-Hands shake worse than ever
-Rigid muscles
-Spontaneous movements
-Group of neurons called substantia nigra (black substance were dying)
substantia nigra
Neurons make a neuron called dopamine
They deliver this to another part of the brain (Striatum
As it dies, they can no longer deliver to another part of the brain
Striatum= controls movement and needs dopamine
Prescribed for Parkinson’s Disease
L Dopa= chemical precursor of dopamine. This penetrates the blood brain barrier and is converted into dopamine inside the brain
Resting Membrane Potential
This is the difference in electrical charge between the inside and outside of the cell
Recording the Membrane Potential
- Tip of one electrode inside neuron and tip of another electrode outside the neuron in the extracellular fluid
2.Both electrode tips in extra cellular fluid= voltage difference is 0
3.Tip of the intracellular electrode is inserted into neuron at rest, -70 millivotls is recorded
Neuron at rest
Not receiving signals from other cells
-70mV is recorded
==Retsing Neuron is about 70 mV less than outisde neuron
Resting Potential
-70mV
-Neuron is polarized (membrane potential is not zero)
Ions
Positively or negatively charged Particles
Resting Neurons: NA+ ions and K+ ions
-There are more NA+ Ions outside the cell than inside
-More K+ ions inside rather than outside
Ion Channels
The unequal distributions of Na+ and K+ ions that are maintained
-Some ion channels are specialized for certain ions
Electrostatic pressure from Resting Membrane Potential
Opposite charges attract, positvely charged ions are attracted to the -70 mV charge inside resting neurons
Random motion for Na+ ions to move down their concentration gradient
1.Ions= constant random motion
1. Particles in random motion tend to become evenly distributed because they are more likely to move down their concentration gradients than up them
2.Move from areas of high concentration to areas of low concentration than vice versa
3.Sodium ions channels in resting neurons= closed, reducing the flow of Na+ ions into the neuron
4.Potassium ion channels are open in resting neurons, but only a few K+ ions exit because the electrostatic pressure that results from the negative resting membrane potential largely holds them inside
1950: Alan Hodgkin and Andrew Huxley
Interested in the stability of retsing membrane potential
=Discovered:
Same rate that Na+ ions leaked into resting neuronms, Na+ ions transported out, and K+ leaked out of resting neurons, K+ transports in
-Ion Transport is performed by exchanging 3 Na+ ions inside and 2 K+ ions outside
Sodium Potassium Pumps
An Ion transporter that exchanges 3 Na+ ions inside the neuron, when two K+ ions go inside
Summary of Status of Na+ and K+ ions in retsing neuron
1) Ions in motion move down their concentration gradients, Na+ enter and K+ tend to exit
2) The negative internal charge created pressure for both Na+ and K+ to enter
3) Then the sodium potassium pumps transport 3 Na+ out for every 2K+ they transport in
Postsynaptic Potentials (PSPs)
Potentials that move the postsynpatic cell’s membrane potential away from the resting state
Neurons Fire
Released into terminal buttons called neurotransmitters
Neurotransmitters
Diffuse across synaptic clefts and interact with specialized receptor molecules on the receptive membranes of the next neuron in the circut
Two effects when neurotransmitter molecules bind to postsynaptic receptors
1) Depolarize the receptive membrane. So this decreases the resting membrane potential from -70 to -67
2) Hyperpolarize it (Increase the resting membrane potential from -70 to -67)
Excitatory Postsynaptic Potentials (Postsynaptic Depolarizations)
These are graded postsynaptic depolarizations that increase the likelihood that an action potential will be generated
Increase likelihood that neurons will fire
Postsynaptic Hyperpolarizations (Inhibitory Postsynaptic Potentials)
They decrease the likelihood that neurons will fire
Graded Potentials
PSPs, EPSPs, and IPSPs
=Amplitudes of PSPs are proportional to the intensity of the signals that elicit them
=Weak signals cause small PSPs and strong signals cause large ones
ESPs and IPSPs travel
They travel passively from their sites of generation at synapses (usually on dendrites or cell body)
Transmission of PSPs has two characteristics:
1) They are rapid: transmitted instantaneously
2)Decremental: They decrease in amplitude as they travel through the neuron. ((Ripple on a pond gradually disappears as it travels outward)
Receptive areas of neurons aee covered
Thousands of synapses
Axon Initial Segment
Actions potentials are generated, this is adjacent to the axon hillock
Axon Hillock
The conical structure at the junction between the cell body and the axon
Threshold of Excitation
The level of depolarization necessary to generate an action potential of around -65 mV
=Sum of depolarzations and hyperpolarizations reaching the axons id sufficient
Action Potential
Massive, but momentary (lasts 1 millisecond). Reverses membrane potential to -70 to about +50. Not a graded response
Graded Response
Their maghnitude is not related to any way to teh intensity of the stimuli that elicited them
(APs ARE NOT THIS)
All or none responses
They occur either to their full extent or do not occur at all
Spatial Summation
Integration of Signals that originate at different sites on the neuron’s membrane
Temporal Summation
The integration of neural signals that occur at different times of the same synapse
Neurons
=Some neurons have a mechanism for amplifying dendritic signals that originate far from their axon
PSPs ate transmitted
Decrementally
Firing of a neuron=firing of a gun
Neuron is stimulated it becomes less polarized until the threshold of excitation is reached and firing occurs
All or none events
=Stimulating a neuron more intensely does not increase the speed or amplitude of the resulting action potential
Parkinson’s Disease
Robert Garcia d”Orta referred himself as a great lizard frozen in a dark, cold, strange world
Tremor at rest symptom
Parkinson’s Disease
Microelectrodes are required to record a neuron’s
Resting Potential
Resting Membrane Potential
Is often about -70 mV
Polarized
Resting state, a neuron is this
Two factors pressure Na+ ions to enter resting neurons through
1) Random motion
2) Electrostatic pressure
Resting state there is a greater concentration of
Na+ Ions ourside the neuron that inside the neuron
Ions pass through neural membrane via specialized pores
Ion channels
Hodgkin and Huxley
Inferred the existence of sodium potassium pumps in neural membrane (first neural transported to be discovered)
Neurotransmitters typically ahve one of two effects on postnaptic neurons
They either depolarize them or hyperpolarize them
Postsynpatic depolarizations are commonly referred in their abbreviared form:
EPSPs
Action Potentials are generated in the axon initial segment and this is adjacent to the
Axon Hillock
Action potential is elicited when the depolarization of the neurons
reach the threshold of exciattion
Unlike postsynaptic potentials (PSPs) that are graded
Action Potentials are all or none responses
Neurons Integrate postsynaptic potentials in two ways:
Through spatial summationa nd through temporal summation
Volate Gated Ion Channels
Ion Channels that open or close in response to changes in the membrane potential
Resting Membrane is relatively impremeable
to Na+ ions because those feew that do pass in are pumped out
Membrane Potential of the axon intital segemnt is depolarized to the threshold of a large EPSP
The Voltage gated sodium channels in the axon membrane open wide, and Na+ ions rush in, and this reverses the membrane potential
This drives the membrane open wide, and Na+ ions rush in, and this drived the membrane potential from -70 to +50 mV
Rapid change in the membrane potential is associated with the influx of
Na+ ions then triggers the opening of voltage gated potassium channels. Then K+ ions are drviven out of the cell through these channels:
1) Relatively High internal concentration
2)AP is near is peak by positive internal charge
After 1 Millisecond
Sodium Channels close
Closure of Sodium Channels
Marks the end of the rising phase of the AP and the beginning of the repolarization phase (which is the result of the continuid efflux of K+ ions)
Repolarization has been achieved
Marks the beginning of the hyperpolarization phase
Opening and Closing of Voltage gated sodium and Potassium channels has three Phases
- Rising Phase
- Repolarization
- Hyperpolarization
AP involves the ions
right next to the membrane
Absolute Refractory Period
Brief period of about 1 to 2 milliseconds after the initiation of an AP during which it is impossible to elecit a second AP
Relative Refractory Period
Followed by Absolute refractory period. This is the period during which it is possible to fire the neuron again but only by applying higher than normal levels of stimulation
Refractory period are responsible for two neural activities
1.APs normally travel alone axons in one direction. Portions of an axon over which an AP has just traveled are left momentarily refractory, an AP cannot reverse direction
2)Responsible for the that the rate of neural firing is related to the intensity of the stimulation
Difference of conduction of APs alon an axon
The conduction of APs along an axon is nondecremental= APs do not grow weaker as they travel alone the axonal membrane
2.APs are conducted more slowly than PSPs
AP Generated
-Travels along the axons as a graded potentail (travels rapidly and decremntally)
Graded Potential Reaches the next Voltage gated sodium channel along the axons and if it if large (exceed threshold of excitation)
=Channels open and Na+ ions rush into the axon and generate. another full blown AP
Sodium Channel at the axon Initial Segment is opened by an EPSP
AP is generated and then that electrical signal travels instantly and decrementally as a graded potential to the next sodium channel along the axon
=Thenn that sodium channel opens to generate an AP and so on down the length of the axon
Eelctrical stimulation of sufficient intensity is applied to a midpoint of an axon
Two APs will be genrated (one AP along the axon back to cell body) and travel along the axon towards the terminal buttons
Antridromatic Conduction
One AP will travel along the axon back to the cell body. Plays a role in certain in the formation of synaptic plasticity
Orthodromic Conduction
Second AP will travel along the axons towards the terminal buttons
Direction of Signals Conducted through a Multipolar Neuron
1.Postsynaptic Potentials are elicted. on the cell body and dendrites
2.PSPs are conducted decrementally to the axon initial segment
3.When the summated PSPs exceed the threshold of excitation at the axon initial segment, an action potential is triggered
4.The AP is conducted nondecrementally down the axon to the terminal button (orthodromic conduction)
5.Arrival of the AP at the terminal button triggers exocytosis
Axons of Neurons are insulated from the extracellular fluid by segments of fatty tissue called
Myelin
Myelinated axons
Ions can pass through axonal membrane only at the nodes of Ranvier
Nodes of Ranvier
Gaps between adjacent myelin segments
Myelination Increases
Speed of axonal conduction
Conduction along the myelinated segments of the axon is
Instantaneous (graded potential), so the signal jumps along the axons from one node of ranvier fo the next
Saltatory Conduction
Transmission of APs in myelinated axons. This the is the conduction of an action potential from one node of ranvier to the next myelinated axon
Velocity of Axonal Conduction
-Conduction is faster in large diameter, and it is faster in those that are myelinated
=Human motor neurons (neurons that synapse on skeletal muscles are large and myelinated (conduct a speed of 60 meters/second)
-Small unmyelinated axons conduct APs of about 1 meter/second
Conduction in Neuron without Axons
APs are the means by which axons conduct all or none signals nondecrementally over relatively long distances
=Some neurons in mammalian brains either do not have axons or have very short ones
=Conduction in these interneuros is only through graded potentials
Hodgkin and Huxley Model
Theory was proposed in 1950s. Was a major advance in understanding of Neural conduction
What model was a major advance in our understanding of Neural Conduction?
Hodgkin Huxley Model in 1950s
=Won a 1962 Nobel prize
=They provided a simple, effective introduction to what we now understand about the general ways in which neurons conduct signals
Problem of Hodgkin and Huxley Model
They are not represnetative of the variety, complexity, and plasticity of many of the neurons in the mammalian brain.
-Study based on the study of squid motor neuron. These neurons are large and easy accessible in the PNS= squid neurons are large, and this is what led to their great easy success
-These same properties make it difficult to apply the model directly to the mamalian brain, and many of these have action not found in the motor neurons
Mounting evidence that neural conduction is not merely due to
Electrical Impulses
=APs or PSPs are accompanied by mechanical impulses, travelling waves of expansion and contraction of neural membrane
Conduction in interneurons lacking axons is typically
Passive and decremental
Saltatory Conduction
The transmission of action Potentials in Myelinated axons
Where are neurotransmitter molecules released?
From specialized sites on buttons into synaptic clefts, where they induce EPSPs or IPSPs in other neurons by binding to receptors on their postsynaptic membranes
Axodendritic Synapse
A synapse of an axon terminal button onto a dendrite
Axosomatic Synapses
Synapses of axon terminal buttons on somas (cell bodies)
Many axodendritic synapses terminate on
The dendritic spines
Dendritic spines
Nodules of various shapes that are located on the surfaces of many dendrites
Astrocyte situated
At the synapse
Tripartite synapse
Most synapses in the brain form this type of synapse. This is a synapse that involves two neurons and an astroglial cell
Synaptic Transmission
Is where all three cell communicate with one another
Dendrodendritic synapses
They are often capable of transmission in either direction
Axoaxonic synapses
These are important because they can mediate presynaptic facilitation and inhibition
An axoaxonic synapse on or near a terminal button
Can selectively facilitate or inhibit the effects of that button on the postsynaptic neuron
Advantage of presynaptic facilitation and inhibition (compared to PSPs)
Can selectively influence one particular synapse rather than the entire presynaptic neuron
Axomyelenic synapse s
This is where an axon synapses on the myelon sheath of an oligodendrocyte
Directed Synapses
Synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity
Non Directed synapses
Are synapses at which the site of release is at some distance from the site of reception
Type of non directed synapse is
Neurotransmitter molecules are released from a series of varicosities (bulges or swellings) alone the axon and its branches and thus are dispersed to surrounding targets
They are often referred to as strings of bead synapses
Large neurotransmitters are
Neuropeptides= and they are short amino acid chains composed of between 3 and 36 amino acids. They are short proteins
Where are small Molecule Neurotransmitter typically synthesized in the cytoplasm?
Of the terminal button and packaged in synaptic vesicles by the button’s golgi complex
Once filled with neurotransmitters, the vesicles are stored in clusters next to the presynaptic membrane
Neuropeptides and other proteins
Are assembled in the cytoplam of the cell body on ribosomes, and then they are packaged in vesicles by the cell’s gologi complex and transported by microtubules to the terminal buttons
How many neurotransmitters do neurons contain?
They contain two neurotransmitters. A neuropeptide in the larger vesciles and a small molecule neurotransmitter in the smaller vesciles
Exytosis
Is the process of neurotransmitter release
What is the process of neurotransmitter exocytosis?
1)Neuron is at rest, synaptic vesicles that cintain small molecule neurotransmitters tend to congregate near sections of the presynaptic membrane that are particular rich in voltage gated calcium channels
2)AP= channels open and Ca2 ions enter the button
3)This triggers a chain reaction that ultimately causes synaptic vesicles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft
Difference in the release of small molecule neurotransmitters from the release of neuropeptides
-Small molecule neurotransmitters= released in a pulse each time an AP triggers a momentary influx of CA2 ions into the presynaptic membrane
Neuropeptides are typically released
gradually in response to general increases in the level of intracellular Ca2 ions, such as might occur during a general increase in the rate of neuron firing.
What are receptors?
Each receptor is a protein that contains binding site for only particular neurotransmitters.
Thus, neurotransmitters can influence only those cells that have receptors for it
Ligand
Any molecule that binds to another is referred to as its ligand of its receptor
Neurotransmitters bind to
Several types of receptors
Receptor subtypes
Different types of receptors to which a particular neurotransmitter. can bind
Advantage of receptor subtypes
They enable one neurotransmitter to transmit different kinds of messages to different parts of the brain
Ionotropic Receptors
Are associated with ligand-activated ion channels
Metabotropic receptors
Typically associated with signal proteins and G proteins (guanosine-triphosphate-sensitive proteins)
