Nerve/Synapse Flashcards
of neurons in nervous system
100 billion
Neurons are _________ cells
Electrical
Communications between neurons take place at sites known as
At specialized sites called synapses
Neural networks are (simple/complex)
Complex
of synapses
Hundreds of trillions
Neurons come in an small/enormous range of shapes and sizes
Enormous
Dendrites
Antenna
Receives input
Synapses occur
Cell Body (soma)
Keeps neurons alive
Nucleus
DNA
Protein synthesis
Axons
Extend from neurons to brain
Propagate signals
Few millimeters to more than a meter
Information moves along the ___
Axon
Resting Membrane Potential
Difference in charge between the inside and outside of the cell
Created by concentration gradient
At rest, the neuronal membrane is highly permeable to __
K+
At rest, the neuronal membrane is less permeable to
The other physiological ions
Where do K+ ions leak to?
Out of cell
Down the concentration gradient
Inside/outside: large concentration of k+
Inside
Inside/outside: low concentration of k+
Outside
What creates the electrical gradient?
Accumulation of unpaired negative ions after sodium leaks
What does electrical gradient result in?
Pull K+ ions back into the cell
When chemical and electrical gradients are equal, the system is _________
At equilibrium
Membrane potential at equilibrium is described by the _____ equation which is ….
Nernst equation
Eion= (2.3RT/zF)(log(ion/ion)
Ek (equilibrium potential for K+)
-90 mV
The resting permeability to K+ is caused by
Leak channels
Leak channels
Proteins that form K+ selective pores through the membrane
Open at the resting membrane potential
Why is the resting membrane potential more positive than Ek
Due to the small inward leak of Na+, which pushes the membrane slightly toward E Na
Membrane potential is determined by
concentration gradients and relative permeabilities of the membrane to different physiological ions
Concentration gradients do/do not change much
do not
Pemeabliities can/cannot change rapidly and dramatically
can
What is the dominant permeability at rest
potassium - Ek
What makes the greatest contribution to the membrane potential
dominant permeability
potassium at rest
Sodium-potassium pump
Pumps sodium out and potassium in against their concentration gradient
Sodium-Potassium uses energy produced
by ATP hydrolysis
How are sodium and potassium gradients maintained
by the sodium-potassium pump
Axons
propagate information from one region of the nervous system to another
Axons transport information by
electrical impulses called action potentials
Action potentials start at ________ propagate down _________ to ________
Action potentials start at the initial segment of the axon propagate down the length of the axon to the presynaptic terminals
Transient depolarizing spike that moves down the axon
Actional Potential
At the action potential peak, the membrane potential approaches the potential of
E of NA
Occurs when the membrane potential depolarizes to a threshold level
initiation of action potential
Threshold
is determined by the properties of ion channels in the axon membrane especially a class of channels called voltage-gated sodium channels
sodium ions flowing into the cell through voltage-gated sodium channels causes
The depolarizing phase of the action potential
Three critical properties of voltage-gated sodium channels
1) They are closed at the resting membrane potential, but open when the membrane depolarizes
2) They are selective for Na+
3) The open channel rapidly inactivates, stopping the flow of Na+ ions
Three sodium channel states
closed, open, inactivated
T/F: The rising phase of the action potential is a regenerative process
T
Depolarization of the membrane to threshold activates
a small fraction of sodium channels, which further depolarizes the membrane, resulting in activation of more sodium channels and so forth
The positive feedback mechanism results very (slowly/rapidly) in …
rapidly
- maximal activation of sodium channels,
- a large sodium influx
- depolarization of the membrane from the resting level to a new level, near Ena
Inactivation of the mechanism results in
termination of the sodium influx, causing the membrane to relax back to the original resting level
Which density is greater: voltage-gated sodium channels or leak potassium channels
voltage-gated sodium channels
T/F: At the peak of the actional potential, the K+ permeability swamps the resting permeability for Na+
F: At the peak of the actional potential, the Na+ permeability swamps the resting permeability for K+
2 factors contributing to the falling phase of the action potential
sodium channel inactivation
delayed activation of voltage-gated potassium channels
What happens when the neuron is firing a lot of action potentials?
- sodium and potassium gradients
- pumps
- sodium and potassium gradients run down faster
- the pumps have to keep up with neuronal activity
Action potential propagation is caused by
spread of electrotonic currents from the site of the action potential, which excited adjacent regions of axion
Action potential propagation is self-regulating/terminating
Action potential propagation is self-regulating
Why does the action potential not move back?
The sodium will not re-excited
Not able to be activated for a small amount of time then returns to the closed state
inactivation of sodium channel
What happens to sodium channels after an action potential
for a few milliseconds, sodium channels are inactivated and the membrane is completely unexcitable
Absolute refractory period
The sodium channels are inactivated and the membrane is completely unexcitable
Relative refractory period
Longer period where the voltage gated potassium channels are open and the membrane potential overshoots its resting level
axons are less excitable and is unlikely to fire an action potential
Neurons send information by means of the ______ and ______ of ______ ________
frequency and pattern of action potentials
ex. Transduction of pressure on skin surface into neuronal activity
T/F: Each action potential is an all-or-none event.
T
Molecular targets for naturally occurring neurotoxins
Sodium channels
Tetrodotoxin
extremely potent inhibitor of sodium
blocks flowing of sodium
Batrachotoxin
a powerful sodium channel hibitor,
appears to bind to an open form of the sodium channel, preventing the closing of the channel
Tetrodotoxin, batrachotoxin, pyrethroid insecticides as well as scorpion and anemone toxins can modulate
Sodium channels
Sodium channels are blocked by therapeutically important drugs for example:
local anaesthetics and some antiepileptic agents.
Local anesthetics Lidocaine Benzocaine Tetracaine Cocaine
Antiepileptics
Phenytoin (Dilantin) Carbamazepine (Tegretol) Lamotrigine
required for survival, especially in situations that require rapid, reflexive responses
rapid propagation of action potentials
propagation rate of the action potential is proportional to
axon diameter
How squids solved the problem of how to send fast-moving signals
making giant axons, 1000 times fatter than our axons
Myelin is formed by
MATCH:
- Schwann cells
- Oligodendrocytes
- PNS
- CNS
Schwann cells (in the PNS) or oligodendrocytes (in the CNS).
Myelin
the insulator that is wrapped around the axon to make a small axon with high conduction velocity
Myelin wraps around the
axon
as an electrical insulator, enabling charge
to travel farther and faster down the axon
Myelin
nodes of Ranvier
periodic gaps in myelin
Nodes of Ranvier sodium channel concentration… why?`
These regions of bare axon contain very high concentrations of voltage-gated sodium channels, enabling the signal to be regenerated at periodic interval
Multiple sclerosis is caused by
loss of myelin
Demyelinated region
White matter
corresponds to regions of the brain and spinal cord that contain mostly myelinated axons
Gray matter
comprises cell bodies, dendrites and synapses
Three main types of synapses
Axondendritic
Axosomatic
Axoaxonic
A single neuron is able to make synapses with many other neurons by
its branching axon
Two axodendritic synapses
spine and shaft synapse
What occurs on the presynaptic Terminal
Activation of voltage-gated calcium triggers neurotransmitter release
What occurs on the postsynaptic spine
Ligand-gated ion channels are postsynaptic receptors for transmission at brain synapses
Steps of chemical synaptic transmission
- The action potential invades
- Calcium channels … resulting in ….
- Synaptic vesicles fuse with … releasing … into ….
- … diffuses across the cleft and activates …. in the …. membrane
- The action potential invades the presynaptic terminal.
- Calcium channels open, resulting in Ca2+ influx into the terminal
- Synaptic vesicles fuse with the presynaptic membrane, releasing the transmitter into the synaptic cleft.
- Transmitter diffuses across the cleft and activates receptors in the postsynaptic membrane.
Synaptic transmission: The action potential invades the
presynaptic terminal
Synaptic transmission: Calciums channels ______ resulting in Ca2+ influx _____ the terminal
Calcium channels open, resulting in Ca2+ influx into the terminal
___________ fuse with the presynaptic membrane releasing the ______ into the ________
Synaptic vesicles fuse with the presynaptic membrane, releasing the transmitter into the synaptic cleft.
_______ diffuses across the cleft and activates receptors in the postsynaptic membrane.
Transmitter diffuses across the cleft and activates receptors in the postsynaptic membrane.
What occurs at the active zone
Calcium-dependent fusion of a synaptic vesicle at an active zone
The postsynaptic response to neurotransmitter is either an ______ or _______
excitatory postsynaptic potential (EPSP)
inhibitory postsynaptic potential (IPSP)
The depolarization of the postsynaptic membrane
excitatory postsynaptic potential
hyperpolarization of the postsynaptic membrane
inhibitory postsynaptic potential
The main excitatory neurotransmitter in the brain
glutamate
Rapid excitatory transmission at synapses is primarily due to the actions of glutamate on two types of ionotropic glutamate receptors:
AMPA receptors
NMDA receptors
AMPA receptors and NMDA receptors are examples of
ionotropic receptors
ionotropic receptors
are ion channels, that open in response to binding of small molecules (e.g. neurotransmitters) to receptor sites on their external surfaces.
_____ receptors are responsible for the “fast” EPSP at excitatory synapses.
AMPA receptors are responsible for the “fast” EPSP at excitatory synapses.
What occurs in AMPA receptors
Glutamate binds to AMPA, allowing Na+ to flow into the postsynaptic spine
EPSP Characteristics
The EPSP is a small, transient depolarization of the postsynaptic spine
The depolarization caused by a single EPSP is ____ millivolts
> a few millivolts
The depolarization caused by a single EPSP lasts
20 msec
Can the depolarization from a single EPSP depolarize the axon
No, the depolarization caused by a single EPSP too small to depolarize the axon initial segment to threshold
How many EPSPs must sum at the initial segment to initiate an action potential
50 to 100 EPSPs
The simultaneous EPSPs can come from either
multiple synapses acting in synchrony and/or from individual synapses, activated at high frequencies
NMDA Receptors key properties
– At resting membrane potentials, the pore is blocked by Mg2+;
depolarization expels Mg2+, enabling the pore to conduct.
– The open pore is highly permeable to Ca2+ as well as monovalent cations.
At -70 mW almost all the synaptic current at an excitatory glutamate synapse is carried through
AMPA receptors
If the postsynaptic membrane is depolarized, a substantial current flows through
NMDA receptors
Highly active excitatory synapses become stronger and involve NMDA receptors
Synaptic plasticity
model of synaptic plasticity
Long-term potentiation (LTP)
High-frequency activity depolarizes the postsynaptic spine, which affects the NMDA receptors by removing the
Mg2+ block of NMDA receptors and enabling them to conduct Ca2+
EPSP/IPSP are larger, hours after induction of LTP.
EPSP
What is toxic to neurons
High concentrations of glutamate
Excitotoxicity
High concentrations of glutamate are toxic to neurons
involves calcium influx through NMDA receptors
______ contributes to neuronal degeneration after stroke and in some neurodegenerative diseases
Excitotoxicity
The main inhibitory neurotransmitter in the brain
is y-aminobutyric acid (GABA)
The postsynaptic receptor responsible for the IPSP
is called the GABAA receptor
The GABA receptor is an _______ receptor
ionotropic receptor
Activation of the GABAA receptor causes an influx of __ ions which __ polarizes the __ synaptic membrane
Activation of the GABAA receptor causes influx of Cl-, which hyper-polarizes the postsynaptic membrane.
A typical cortical neuron receives ________ of synaptic inputs
thousands of synaptic inputs, some excitatory, others inhibitory
Excitatory inputs tend to be located on
dendritic spines
inhibitory inputs are often clustered on or near
the cell soma, where their inhibitory effect is maximal
Whether or not a neuron fires an action potential at any given moment depends on
the relative balance of EPSPs and IPSPs
T/F The output of the neuron the all-or-none firing of action potentials down the axon
T
What type of receptors are G-protein coupled receptors, GPCRs
Metabotropic receptors
Glutamate synapses have ionotropic receptors (AMPA and NMDA receptors) or metabotropic glutamate receptors (mGluR’s) or both
both ionotropic receptors (AMPA and NMDA receptors) and metabotropic glutamate receptors (mGluR’s)
What generates a chemical signal (second messenger) inside the postsynaptic spine?
Activation of mGluR’s by glutamate
2nd messengers activate
a range of cellular proteins, including ion channels, protein kinases and transcription factors
Glutamate and GABA activate
both ionotropic and metabotropic receptors
Many types of neurotransmitters interact mainly, or entirely with
metabotropic receptors
dopamine, serotonin and norepinephrine are examples of
neuromodulators
They are not directly involved in the fast flow of neural information, but modulate global neural states, influencing alertness, attention and mood.
neuromodulators
Neurons that release neuromodulators often originate in
small brainstem or midbrain nuclei
The axons of the neurons that release neuromodulators project ….
diffusely throughout the brain
Important targets for a wide range of drugs
such as antidepressants
Neuromodulator systems
The prozac antidepressants affects
serotonergic transmission
antidepressants such as amphetamines, cocaine and other stimulants typically affect … (which transmitters)
dopamine and norepinephrine transmission
