Chapter 3 Flashcards
Neurons & Glia Resting Membrane Potential Action Potentials The Synapse
The Neuron Theory Battle
Golgi’s Reticularist Doctrine
versus
Cajal’s Neuron Doctrine (wins)
Neurons
–Functional unit of the nervous system
–Specialized for the reception, conduction and transmission of electro-chemical signals
Dendrite
Collect incoming information at synapses from target neurons
Axon
Transmits information at the synapse to dendrites of other neurons or to an effector cell
Conducts action potentials (Conduction zone)
Branches to form axon collaterals
Axon diameter varies substantially across species
Diameter related to speed of signaling
Cell Body (Soma)
Integrates information and generates outgoing signals
–Provides metabolic (energy) and synthetic (protein) support
–Acts to “gate” information flow to and from other neurons
–Integrates signals from many sources of input (Integration zone)
Cytoplasm
Consists of the the cell’s cytosol and organelles.
Nucleus
Contained in nuclear envelope
Gene Expression
23,000 human genes
Transcription
mRNA assembly
Translation
Assembly of proteins from 20 amino acids
Neuronal Cytoskeleton
Structural support for maintenance of neuronal shape
Microtubles
responsible for moving material around cell
Neurofilaments
provide structural support to axon
Microfilaments
may assist in reorganization of neuronal branches
Cell Membrane
•Defines boundary of cell •Intracellular/Extracellular environments are different •Double layer of lipid (fat) molecules •Contains protein molecules –Receptors –Channels –Transporters
The two basic cellular processes:
1) Protein Synthesis
2) Energy Production
Dendritic Tree
- Collection of dendrites from single neuron
- Receives input from other neurons (Input zone)
- Inputs may number in the thousands
Dendritic Spines
- Contact point between axon and dendrite.
- Sensitive to the type and amount of synaptic activity.
- Dynamic: synaptogenesis can occur on rapid time scale.
- External and internal factors influence spine morphology and density.
- In an Enriched environment, the dendritic spines are more numerous and thicker than those seen in individuals living in a less stimulating environment.
- Estrous cycle: Peak density of dendritic spines occurs during ovulation
Axon Hillock
where axon merges with the cell body
Myelin
Provides insulation, allowing for faster signaling and for smaller diameter axons.
-No need for ion channels under myelin sheath—reduces work done by sodium-potassium pumps.
-Fewer ions move through axon membrane in myelinated than unmyelinated axons.
Myelin is fatty and white-collored.
Nodes of Ranvier
Bare space of a myelinated axon’s membrane.
Ions move through channels only at nodes.
Axon Length
Axons vary in length
- Local circuit neurons: short axons
- Projection neurons: very long axons
Collaterals
branches that arise from axon
Terminal
swelling at end of axon collateral
Terminal contains mitochondria (provide energy) and synaptic vesicles containing neurotransmitter
Synapse
point of contact between the axon terminal and the somatic or dendritic membrane (spine) of another neuron.
Information passed directionally from presynaptic to postsynaptic cell.
The 3 principal components of a Synapse
presynaptic membrane, postsynaptic membrane, synaptic cleft
Classification of Neurons
Length of axons
−Local circuit: short axons
−Projection: long axons
Shape (Structure)
−Monopolar
−Bipolar
−Multipolar
Function
−Motor
−Sensory
−Interneuron
Sensory Neurons
Carry info from body to brain and spinal cord (Afferent)
Motor Neuron
Carries info from brain and spinal cord to muscles and organs (Efferent)
Interneuron
Connects one neuron to another in brain or spinal cord
Glia
−Non-neural
−9X more numerous than neurons
−Provide physical and functional support to neurons
−May have many important clinical implications
Schwann Cell
Myelinates axons in the Peripheral Nervous system.
One cell contributes to only one axon.
Schwann cells help guide the regrowth of damaged axons.
Oligodendrocyte
Myelinates axons in the Central Nervous system.
One cell contributes to several axons.
Microglia
Cleans up debris in the Central Nervous system.
Sense molecules associated with cellular damage and digest the debris.
Microglia release substances that can lead to neuroinflammation, possibly contributing to multiple neurodegenerative diseases, including Alzheimer’s disease and multiple sclerosis.
Astrocyte
Found in the Central Nervous system.
Provides Structural and nutritional support for neurons
Isolates the synapse
Cleans up debris
Play a role in the blood brain barrier (don’t allow highly charged, too large. or fat-insoluble substances)
May play a role in signaling and synaptogenesis
Astrocyte
Found in the Central Nervous system.
Provides Structural and nutritional support for neurons
Isolates the synapse
Cleans up debris
Play a role in the blood brain barrier
May play a role in signaling and synaptogenesis
Ingredients of Intracellular and
Extracellular Fluid
• Water
– H2O
• Ions – Charged particles Potassium – K+ Sodium – Na+ Calcium – Ca2+ Chloride – Cl- Protein anions – A-
Ion Concentrations
Because of the distribution of ions and other charged particles the inside of the neuron, neurons are negatively charged relative to the outside
Relative Ion Concentrations
Higher Inside the Cell:
Protein anions
Potassium
Higher Outside the Cell:
Sodium
Chloride
Calcium
Resting Membrane Potential
The difference in charge between the inside and outside of the membrane of a neuron at rest.
At rest, the inside of the cell is about –70 mV lower than outside of cell
Potential =
Voltage
Diffusion
Molecules will move from areas of high concentration to areas of low concentration.
Diffusion pressure moves molecules along a Concentration Gradient.
Electrical Force
Charged molecules or ions will be attracted to areas of opposite charge and repelled by areas of like charge.
Like charges repel each other.
Opposite charges attract each other.
Selective Permeability
Different channels and receptors “gate” specific ions (i.e., they are selectively permeable).
Resting Membrane Potential
•Resting membrane potential is about -70mV
•Resting membrane potential due to:
−Selective permeability of membrane
−Uneven distribution of ions on the inside vs. outside of the cell
The neuron is polarized in it’s resting state
Depolarization
membrane potential becomes less negative
Hyperpolarization
membrane potential becomes more negative
Action Potentials
method by which neurons communicate
–When the axon hillock region becomes more positive, to about -65 mV from -70, an AP is generated
Action Potential properties, once threshold reached
–Rising phase
•Na+ enters neuron
•Depolarization
–Overshoot
•Neuron positive inside
relative to outside
–Falling phase
•K+ exits neuron
•Hyperpolarization
Properties of Action Potentials
−All or None
−AP amplitude & speed is constant
−Each AP followed by refractory period
Voltage-Gated Channels
- Voltage-gated Na+ and K+ channels open and close as a function of the neuronal membrane potential
- They are located along axon hillock, axon membrane and terminals
- Their rapid opening and closing is responsible for AP initiation and propagation
Absolute Refractory Period:
–Neuron can NOT fire again
–Limits how frequently a neuron can fire
–Accounts for unidirectional nature of action potential
–Na+ channel can only open again once membrane potential hyperpolarizes
Neural information code
Pattern (temporal code)
Frequency (rate code)
Relative Refractory Period
–Membrane potential becomes more negative than resting membrane potential
–Neuron can fire again, but only with strong stimulus
–Plays a role in intensity coding, i.e. stimulus intensity coded by firing rate
Action Potential Propagation
Remember, once a voltage-gated Na+ channel opens and closes, it can only be opened again once the membrane potential has hyperpolarized. In this way, the AP cannot flow backwards.
The Speed of an Action Potential depends on
−Myelination: myelinated is faster than unmyelinated
−Axon diameter: large is faster than small
Invertebrate axon: 11 mph
Human axon: 268 mph
Axon Terminal
AP invades axon terminal; the signal changes from electrical to chemical
Ion Movement During an Action Potential
During an action potential, positive ions first flow into the axon. There is little to no net change in distribution of the negative ions.
When the inside of the axon accumulates maximal levels of positive charge, positive ions begin to flow out of the axon.
When the action potential reaches the axon terminal, it triggers the release of neurotransmitters.
Charles Sherrington
coined term Synapse (1897)
Soups vs. Sparks
- Physical nature of synaptic transmission
- Chemical vs. Electrical transmission
Soup vs Spark Controversy: Is synaptic transmission generally chemical or electrical?
Controversy lasted from 1936-1950’s
J.C. Eccles (one of Sherrington’s last students)
•1st an electrical impulse passed directly from the presynaptic axon to postsynaptic cell
• then a more prolonged action of Neurotransmitter
Experiments by B. Katz and many colleagues particularly S. Kuffler refuted direct electrical transmission at NMJ
irreducible synaptic delay => not electrical
endplate and synaptic potentials precede the AP
subthreshold stimulation led to a graded postsynaptic response rather than the all or none response like AP presynaptically
Eccles conceded NMJ chemical and later also showed CNS inhibition involved the same properties, therefore also chemical.
Soup vs Spark Controversy
The ‘soup vs. spark’ debate (1930s): the origin of modern psychiatric & neuropharmacology
Neurons communicate via synapses, which depend on a chemical substance called a neurotransmitter to pass along the messages. This theory was first established by Henry Dale and Otto Loewi; it was called ‘soup’ camp, for there was a chemical molecule involved.
John Eccles theorized that the message transmission between neurons had to be an electrical phenomenon, thus called ‘spark’ camp.
Bernard Katz fled Hitler’s Germany to England and witnessed a ‘stand-up fight’ between John Eccles and Henry Dale and the chairman (at University College at London) “acting as a most uncomfortable and reluctant referee.” The sparkers were in the wrong.
The experimental results were the same in both camps; it was the different interpretation and theory that led to the radically different conclusions.
John Eccles later discovered synaptic inhibition in the spinal cord. GABA is the main inhibitory transmitter in brain. Many tranquilizers and general anesthetics bind to GABA receptors, producing a calming effect by enhancing the receptors’ inhibitory function. The drug-made equanimity should be credited to John Eccles, who was once so wrong in the soup vs. spark debate. He went on to receive a Nobel in 1963, nearly 30 years after Henry Dale and Otto Loewi (the soupers) got theirs.
Neurotransmitters regulate information transfer: Vagusstoff
Vagusstoff (German for “Vagus Substance”) refers to the substance released by stimulation of the vagus nerve which causes a reduction in the heart rate (slowed heart beat).
Discovered in 1921 by physiologist Otto Loewi, vagusstoff was the first confirmation of chemical synaptic transmission and the first neurotransmitter ever discovered.
It was later confirmed to be acetylcholine, which was first identified by Sir Henry Dale. In 1936 Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Dale.
axoaxonic synapse
one between the axon of one neuron and the axon of another neuron.
axodendritic synapse
one between the axon of one neuron and the dendrites of another.
axodendrosomatic synapse
one between the axon of one neuron and the dendrites and body of another.
dendrodendritic synapse
one from a dendrite of one cell to a dendrite of another.
electrotonic synapse
a special type of gap junction found in tissue such as the myocardium.
Steps in Synaptic Transmission
?
Calcium and the Synapse
- Voltage-gated calcium channels open in response to AP
- Calcium must be cleared prior to arrival of next AP
Vesicular Release
Exocytosis: Entering calcium releases vesicles from protein anchors and stimulates fusion with membrane.
Endocytosis: Excess membrane pinches off to form new vesicle.
Neurotransmitters
endogenous chemicals that transmit signals from a neuron to a target cell across a synapse.
Types of Neurotransmitters
–Small molecules: serotonin, norepinehprine, epinephrine, dopamine, acetylcholine
–Amino acids: GABA, glutamate
–Neuropeptides: secretin, oxytocin
–Soluble gases: nitric oxide, carbon monoxide
Activation of Receptor Sites
Neurotransmitter molecules diffuse into and throughout the synaptic cleft
Neurotransmitters bind to specific receptors in a lock and key fashion
–Post-synaptic receptors
–Pre-synaptic receptors (autoreceptors)
Autoreceptors
An autoreceptor is a receptor located in presynaptic nerve cell membranes which serves as a part of a negative feedback loop in signal transduction.
NT synthesis and release regulated (usually inhibited) by presynaptic autoreceptors
Terminal autoreceptor:
reduce NT synthesis and release
Somatodendritic autoreceptor
hyperpolarizes neuron, reducing AP spiking rate
Terminating NT Signal Can occur by which 3 Methods?
- Diffusion
- Deactivation Enzymes
- Reuptake
Describe the Two Receptor Types
Voltage-gated Receptors: activated based on changes in the membrane potential
Ligand-gated Receptors: activated by the binding of specific molecule or neurotransmitter
Postsynaptic Receptors
Ionotropic or Metabotropic
Ionotropic Receptor
- Opens channels directory
- Relatively fast
- Relatively short
- Effects are localized
Metabotropic
- Opens channels indirectly
- Uses chemicals called second messengers
- Relatively slow acting
- Relatively long-lasting effects
- Effects are more widespread and varied
Local Effects of Receptor Activation
•Excitatory Postsynaptic Potential (EPSP):
–Opens sodium channels
–Depolarizes dendrites and cell body
–Facilitates likelihood of Action Potential
•Inhibitory Postsynaptic Potential (IPSP):
–Opens potassium or chloride channels
–Hyperpolarizes dendrites and cell body
–Decreases likelihood of Action Potential
Inhibitory Postsynaptic Potential (IPSP):
–Opens potassium or chloride channels
–Hyperpolarizes dendrites and cell body
–Decreases likelihood of Action Potential
Excitatory Postsynaptic Potential (EPSP):
–Opens sodium channels
–Depolarizes dendrites and cell body
–Facilitates likelihood of Action Potential
Neural Integration
Combining a number of individual signals into one overall signal
Two ways:
•Over time (temporal summation)
•Over space (spatial summation)
Effect:
•Summation of EPSPs: action potential is more likely
•Summation of IPSPs: action potential is less likely
Temporal Summation
An action potential lasts ~1ms
A graded potential lasts ~5-10ms
Thus, APs that occur very rapidly can build on one another
Graded Potentials
Local Potentials……
Spatial Summation
Combines all EPSPs and IPSPs occurring at different locations on the dendrite and cell body
EPSP/IPSP integration:
analogue signal is summed over time and space
Action Potentials are Binary signal
Neuromodulation
Presynaptic Facilitation: Increases amount of neurotransmitter released by the postsynaptic terminal button
Presynaptic Inhibition: Reduces amount of neurotransmitter released by the postsynaptic terminal button
Electrical Synapses
AKA gap junctions
Fast transmission
Bi-directional
Do not typically occur at axon terminals
Negative Feedback
Occurs when the result of a process influences the operation of the process itself in such a way as to reduce changes. Negative feedback tends to make a system self-regulating; it can produce stability and reduce the effect of fluctuations. Negative feedback loops in which just the right amount of correction is applied in the most timely manner can be very stable, accurate, and responsive.
Steps in Synaptic Transmission
Action Potential reaches the axon terminal
Calcium ion channels open, calcium flows into cell.
Calcium, causes vesicle to release from microtubules
Synaptic vesicles fuse with axon membrane at release sites
Vesicles open, releasing neurotransmitters into the synaptic gap
Vesicle material is recycled
Vesicles either return to neuron cell body via retrograde transport or are refilled at the axon terminal
Graded potentials
Graded potentials are changes in membrane potential that vary in size, as opposed to being all-or-none. They arise from the summation of the individual actions of ligand-gated ion channel proteins, and decrease over time and space. They do not typically involve voltage-gated sodium and potassium channels.
