Krueger 1 Flashcards
what are synapses?
specialized zone of contact at which one neuron communicated with another
how many neurons in human brain?
avg human received how many synapses?
number of synapse in human brain?
neurons= 10^11 - 10^12
1000 synapses in avg. neuron
synapses in human= 10^15 - 10^16
2 types of synapses & explain
1) electrical- junctions b/w neurons permitting direct, passive flow of electrical current
2) chemical- junctions between neurons that comminicate via secretion of neurotransmitters
- chemical agents released by presynaptic neuron produced secondary flow in postsynaptic neurons activating specific receptors
neurotransmitters undergo similar cycle (4 steps)
1) synthesis and packaging into synaptic vesicles
2) release from presynaptic cell
3) binding to post synaptic receptors
4) rapid removal and/or degradation
influx of ____ through voltage-gated channels triggers secretion of ______
CALCIUM triggers secretion of NEUROTRANSMITTERS
rise in Ca concentration, causes what?
- synaptic vesicle to fuse with presynaptic plasma membrane and release contents into space between pre and post synaptic cells
electrical synapses are ___ _______
gap junctions
structure of gap junctions (electrical synapses)
- plasma membrane closely apposed (3nm)
- precisely aligned, paired channels= connexons (made up of connexins)
how do connexins form pore that connects cells (electrical synapse)
- 6 presynaptic connexin align with 6 postsynaptic connexins to form pore between 2 cells
(electrical synapse) gap junctions consist of wht complexes, and they are formed by?
- hexameric complexes
formed by connexons coming together (present in pre/post synaptic membranes)
components/formation of gap junction (how much of each thing)
(electrical synapse)
Connexin (x6) --> connexon (hemichannel)- (x2) --> gap junction channel (x 10^2 - 10^3) --> GAP JUNCTION
different connexin isoforms determine….?
electrical synapse
transmission properties of the electrical synapse
what diffuses through neuronal gap junctions (2)
electrical synapse
- all ions (ex: K, Na, Ca, Cl)
- small molecular weight compounds (ex: 2nd messengers: cAMP, IP3)
experiment: patch clamping pair of electrical coupled neurons
- type of current injected (depol/hyper)
- when see AP?
2 electrically connected neurons
- inject depolarizing current and neuron fires AP
- polarizes to threshold and see AP
what happens at post synaptic neuron (patch clamping experiment)
- speed of Na
- see depolarization in post synaptic
- no AP
- the gap junctions (small openings), only fraction of Na can make it across the junction into postsynaptic neuron, the depolarization would be much smaller than presynaptic neuron
- very fast b/c ass soon as AP, theres Na flowing into cell
inverse experiment of patch clamping
- inject hyper-polarizing current into presynaptic current
- positive charged ions will flow from other side, hyper-polarizing neuron
what is end plate current (patch clamp experiment)
- direction current flowing, causing..?
macroscopic current resulting from summed opening of many ion channels
- current flowing= inward, causes post synaptic membrane potential to depolarize
- depolarizing change inpotential, triggers postsynaptic AP by opening voltage-gated Na and K channels
directionality of electrical synapses transmission
- what does it depend on?
bidirectional
- electrical synapses are rectifying due to voltage-dependent of gap junction channel opening
- current can flow in either direction across gap junction, depending on which member of coupled pairs is invaded by AP
velocity of electrical synapse transmission
- rapid
- synaptic latency in order of 1ms
- b/c passive current flow across gap junction is instantaneous
sign and amplitude of transmitted changes of electrical synapses
- which is better transmitter (slow/fast potential change)
same sign, smaller amplitude
- ex: 10mV hyperpolarization presynaptically may lead to 1mV hyperpolarization postsynaptically
- slow potential changes are better transmitted than fast potential changes (ex: AP)
general purpose of electrical synapse?
synchronize electrical activity among populations of neurons
regulation of electrical transmission
gap junctions
- most gap junction channels are closed, regulated to alter fraction of open channels
connexin phosphorylation
- and example
(electrical synapse- regulation of transmission)
extracellular signals activate protein kinases which phosphorylate connexins
- depending on connexin type, phosphorylation can have opposite effect and tend to open cap junction channels
ex horizontal cells: D1 receptor–> adenyly cyclase–> cAMP–> protein kinase A–> phosphorylation of connexins–> gap junction channels less open
gap junction response to intracellular Ca concentration
electrical synapse- regulation of transmission
gap junctions close in response to pathologically high Ca concentration
differences in membrane potential between electrically connected cells
large differences in membrane potential between electrically connected called tend to close gap junction channels
- dependent on connexin composition
- if membrane depolarized, can lead to closing of gap junction channels
electrical synapses in aplysia californica
motor neurons in control of ink discharge are connected via electrical synapses
- allowing them to fire synchronously, providing rapid and complete ink discharge
electrical synapses in fish
- mauthner neurons are large reticulospinal neurons in fish and amphibia that mediate escape responses
- in teleosts, these neurons receive mixed electrical and chemical synaptic input from auditory afferents
electrical synapse in retina (mammals)
- allow for some processing of visual info
- horizontal cells are for lateral inhibition of input, they are couples and allow to activate at the same time
- horizontal cells get uncoupled, and close electrical synapse, less inhibition, photoreceptors can transmit info to bipolar cells (allow to see in dark)
electrical synapses in neocortex
- have excitatory projection neurons and inhibitory neurons (GABA)
- interneurons, similar functions, connected via electrical synapses, activate in similar way
- if one interneuron is depolarized from incoming chemicals, sends depolarization to connecting neurons so they can depolarize the same way
(chemical synapses structure)
- presynaptic bouton
specialization of presynaptic neuron containing cellular components required for the secretion of neurotransmitter
(chemical synapses structure)
- synaptic vesicle
membrane vesicle of 35-50nm diameter
- contains 1000s of neurotransmitter molecules
- small membrane bounded organelles within presynaptic terminal
(chemical synapses structure)
- active zone
proteinacious structure at presynaptic membrane
- required for efficient exocytosis of neurotransmitter
- provide protein to fuse to plasma membrane to release neutotransmitters
(chemical synapses structure)
- synaptic cleft
and width
extracellular space between presynaptic and postsynaptic membrane
- width 20-40nm
(chemical synapses structure)
- postsynaptic specialization
- proteinaceous structure at the postsynaptic membrane
- contains neurotransmitter receptors, proteins of intracellular signalling cascades (ex: kinases) and scaffolding proteins- which link receptors and signalling proteins to cytoskeleton
3 reasons why chemical synapses are not created equally
1) structure of postsynaptic specialization is different in inhibitory and excitatory synapses
2) vesicles containing peptide and monoamine neurotransmitters have a different ultrastructural appearance
3) different pre and postsynaptic structures can participate in synapse formation
(chem. synapses not created equal #1)
- the different structures of postsynaptic specialization between inhibitory and excitatory synapses
excitatory- asymmetrical synapses
- Grays Type I
- post synaptic specialization is thicker than presynaptic
inhibitory- symmetrical synapses
- Grays Type II
- thickness of pre and postsynaptic specialization is close to same
(chem. synapses not created equal #2)
- vesicles containing peptide and monoamine neurotransmitter have a different ultrastructural appearance (3 different types)
1) small synaptic vesicle with little electron density
- amino acid neurotransmitters, acetylcholine, purine neurotransmitters
2) small, electron dense- vesicles
- monoamine neurotransmitter
3) large electron-dense vesicles: synapses also contain regular synaptic vesicles with non-peptide neurotransmitter
- peptide neurotransmitter
(chem. synapses not created equal #3)
- different pre and post synaptic structures can participate in synapse formation (6 types)
1) axospinous synapses
2) axodendritic synapses
3) axosomatic synapses
4) axo-axonic synapses
5) dendrodentritic synapses
6) neuromuscular junctions
(chemical synapses)
- axospinous synapses
synapses of axonal boutons onto spinous protrusions of dendrites
- excitatory (glutamatergic) synapses
(chemical synapses)
axodendritic synapses
synapses of axonal boutons onto dendritic shafts
- inhibitory or excitatory synapses
(chemical synapses)
axosomatic synapses
synapses of axonal boutons onto neuronal soma
- frequently inhibitory synapses
(chemical synapses)
axo-axonic synapses
synapses of axonal boutons onto axons or another axonal bouton
- inhibitory synapses
(chemical synapses)
dendrodentritic synapses
synapses of dendritic segments containing synaptic vesicles onto another dendrite
- often reciprocal inhibitory synapses
(chemical synapses)
neuromuscular junctions
of axonal boutons onto muscle fiber
- excitatory (cholinergic) synapses
(chemical synapses)
synapses made on axons..
exclusively inhibitory
- can inhibit the release of neurotransmitter on the synapse
(chemical synapses)
synapses between dendrites…
make synaptic contact
- often inhibitory and reciprocal
transmission of chemical synapses
- sequence of events (7)
1) an AP arrives @ presynaptic bouton, voltage-gated Na channels open
2) voltage gated Ca channels open, and Ca flows into the cytosol
3) increase cytosolic [Ca] causes synaptic vesicle docked to active zone to fuse with the plasma membrane
- neurotransmitter is released into synaptic cleft (via exocytosis)
4) neurotransmitter binds to
- ionotropic receptors (lead directly to opening ion channels)
- metabotropic receptors (leading to opening/sometimes closing ion channels via activations of GPCR (and 2nd messenger cascade)
5) postsynaptic current leads to a postsynaptic potential (change in potential of postsynaptic membranes)
6) removal of neurotransmitter by glial re-uptake or enzymatic degradation
7) retrieval of vesicular membrane from plasma membrane
ionotropic receptors
- speed of postsynaptic responses
chemical synapses
ligand-gated ion channels
- the ligand (neurotransmitter) binds to an extracellular site, leading to a conformational change in receptors membrane spanning domain, which opens ion channel
- mediate rapid postsynaptic effects
ioniotropic receptors allow the passage of..
- they are ion selective
allow
Cl) or (Na and K) or (Na, K and Ca
metabotropic receptors
- speed of postsynaptic responses
chemical synapses
G-Protein Coupled Receptors (not ion channels themselves)
- ligand (neurotransmitter) binds to extracellular site, leading to a conformational change in receptors membrane spanning domain, which activated a G-Protein bound to the receptor
- postsynaptic responses to activation are usually slow and long-lasting
the activated G-protein dissociated from receptors and either…
(metabotropic receptors- chemical synapses)
1) binds DIRECTLY to an ion channel and modulated its conductance
or
2) bind to effector proteins/enzymes that modulate the concentrations of SECOND MESSENGERS (cAMP, cGMP or IP3) which modulate ion channels
- G-protein or second messenger-modulated ion channels are usually ion-selective
similar function of both ionotropic and metabotropic receptors
(chemical synapses)
lead to conduction of ions across the postsynaptic plasma membrane
(where there is ion flow there is change in postsynaptic terminal)
what process turn chemical transmission off?
- explain (7)
1) voltage gated Na channel: inactivate
2) voltage-gated K channel: open, repolarizing presynaptic membrane
3) voltage-gated Ca channel: close after repolarization of presynaptic membrane
4) ion pumps: (ex: Na/K- ATPase), re-establish ion gradients across the presynaptic membrane
5) neurotransmitter: is removed from synaptic cleft by transporters in neurons and surrounding glial cells
6) some ionotropic receptors: desentsitize and close in the continued presence of their ligand
7) postsynaptic potentials: spread throughout the dendrite and soma, and eventually dissipate (of threshold to activate voltage-gated Na channels is not reached)
time course of postsynaptic currents and potential
– of single ligand gated ionotropic receptors and synapse
(chemical synapses)
single ligand- gated ionotropic receptors:
neurotransmitter causes channel to open
-channel is open only for few milliseconds, as the ligand unbinds and diffuses away
synapse: many neurotransmitter molecules exocytosed many ligand-gated channels open nearly simultaneously
- variability in timecourse of ligand unbinding causes some to channels to close later
time course of postsynaptic current and potential
chemical synapses
post synaptic current= sum of all channel currents
- fast rise tome (near simultaneous ligand binding)
- slower time to decay (variability in ligand unbinding)
postsynaptic potential
- similar, slightly slower time course
flux of ions across membrane is determined by… (which is)
chemical synapses
electrochemical gradient
- the sum of membrane potential and concentration gradient
reversal potential for an ion if..
chemical synapses
membrane potential and concentration gradient oppose each other and are of same strength
- electrochemical gradient is zero
direction of postsynaptic current is calculated by…
chemical synapses
using membrane potential and reversal potential of ligand gated ion channel
- if reversing potential is more positive than membrane potential –>net current is inward (negative)
- if reversing potential is more negative than membrane potential–> net current is outward (positive)
amplitude of postsynaptic current depends on (2)
chemical synapses
1) number of conductance of open ligand-gated ion channels
2) magnitude of difference between membrane potential and reversal potential
opening of ligand gated ion channels during synaptic transmission causes…
(chemical synapses)
postsynaptic membrane potential to change in the direction of the reversal potential of that ion
more different the membrane potential from reversing potential the _____ the current
larger the current
when does a reversal potential occur (what is net current have to be?)
(chemical synapses)
reversal potential of an ion channel is the membrane potential at which the net current through the channel is ZERO
if an ion channel is selective for single ion, its reversal potential is _____,
the reversal potential can be calculated using?
reversal potential is equilibrium potential
- membrane potential at which there is no electrochemical driving force for this ion
- Nerst Equation
Erev= reversal potential
Vm= membrane potential
Erev= (RT/zF) ln [ion]o / [ion]i
if an ion channel is permeable to 2 or more ions, how do you calculate
its reversal potentail is somewhere inbetween the equilibrium potentials for the indivudual ions
- calculate using Goldman Equation
Erev= 58log (Pk[K]o+PNa [Na]o+PCl[Cl]i) / (Pk[K]i+PNa[Na]i+PCl [Cl]o)
post synaptic currents and potentials change ____ with membrane potential
linearly
post synaptic currents and potentials are called excitatory potentials if…
(chemical synapses)
excitatory postsynaptic currents and potentials (EPSC and EPSP)
- if they increase the likelihood of a postsynaptic AP occurring
- synapses at which neurotransmitter release leads to the generation of EPSP are called excitatory synapses
when does the post synaptic potential facilitate action potential, and when is it excitatory? (with reversing potential)
(chemical synapses)
- if the reversal potential of the ligand-gated ion channels carry the post synaptic current is MORE POSITIVE than the action potential
2 examples for excitatory synapses
chemical synapses
1) glutamatergic synapses in the CNS
- contain Na/K- permeable glutamate receptors
2) neuromuscular junctions
- contain Na/K- permeable acetylcholine receptors
postsynaptic currents and potentials are called inhibitory if…
IPSC and IPSP if they decrease the likelihood of a postsynaptic action potential occurring
- synapses at which neurotransmitter release leads to the generation of IPSP= inhibitory synapses
when does the post synaptic potential inhibit the action potential generating?
if reversal potential of ligand-gated ion channels carrying postsynaptic current is MORE NEGATIVE than the action potential threshold
- if Erev Vm, IPSP is depolarizing so exceed threshold– shunting inhibition
what is the shunting inhibition of IPSP?
chemical synapses
if Erev > Vm
- IPSP is depolarizing
- tends to keep membrane potential at value more negative than the AP threshold (Erev)
- making harder for adjacent excitatory synapses to elicit action potential
- makes inhibitory
example of inhibitory synapses
- which contain what receptors?
(chemical synapses)
GABAergic synapses in the CNS
- contain Cl permeable GABA receptors
SUMMARY
directionality (electrical vs chemical)
electrical= bidirectional
chemical= unidirectional
- transmission pre to post synaptic terminal
SUMMARY
synaptic delay (electrical vs chemical)
electrical is
SUMMARY
direction of postsynaptic potential change
electrical vs chemical
electrical: same as presynaptic potential change
chemical: either hyperpolarizing or depolarizing
- depends on Vm and Erev of postsynaptic ligand-gated ion channels
SUMMARY
amplitude of postsynaptic potential change
electrical vs chemical
electrical: fraction of presynaptic potential change; slow potential changes transmitted better
chemical: depends on Vm and Erev of ion channel involved
and on number and conductance of opened channels
SUMMARY
transmission of presynaptic sub threshold activity, yes/no
electrical vs chemical
electrical: YES
chemical: NO
- transmission required presynaptic action potential
- exception: photoreceptors on bipolar cells in retina, and hair cells can release neurotransmitter in response to graded receptor potentials
What signals can be relayed by electrical synapses? What functional roles do electrical synapses
have? Is transmission at electrical synapses regulated?
SIGNALS - Electrical synapses contain gap junction channels that permit passage of Na+, K+, Cl-, and Ca2+ from
one cell to the other. Second messengers such as cAMP and IP3 can also diffuse through gap junction
channels
FUNCTION - (a) Fast escape responses in invertebrates and vertebrates,
(b) synchronization of activity in
neurons of the same type (especially inhibitory interneurons, such as in the cortex and the retina)
REGULATION: Conductance of gap junction channels is regulated by, e.g., phosphorylation of connexins
What is the reversal potential (Erev) of ion channels at a synapse?
How is the postsynaptic current related to membrane potential (Vm) and Erev ?
- The reversal potential of ion channels at a synapse is the membrane potential at which the net current
through the channels is zero. - If the membrane potential is more negative than the reversal potential, there is a net inflow of positively charged ions into the cell (or a flow of negatively charged ions out of the cell, depending on the ion selectivity of the channels).
- If the membrane potential is more positive than the
reversal potential, there is a net outflow of positively charged ions out of the cell (or an inflow of negatively
charged ions). - In every case, the membrane potential moves towards the reversal potential of the ion channels
