lecture 12 modulation Flashcards
things that can cause synaptic strength to change
diseases (myasthenia gravis, startle disease)
drugs (therapeutic, recreational)
prior or ongoing activity (experience changes thoughts and actions by altering synaptic function
what mechanisms lead to altered synaptic strength
addition or loss of synaptic connection
(can take hours to occur)
growth or shrinkage of synapse
(synaptic current directly proportional to number of open receptors)
rapid change in synaptic efficacy with no structural change
(no new proteins)
how to measure synaptic strength between 2 neurons
1) stimulate axon with electricity
2) fires action potential
3) releases neurotransmitters
4) epsp detected by recording electrode in post synaptic cell
how is facilitation different from temporal summation
facilitation piggybacks but the amplitude gets bigger every time and the second one starts after the first has gone back to rest (presynaptic because it relies on residual calcium)
vs
temporal summation where the epsps piggyback on top of each other and the next one starts before the first one has ended (postsynaptic because it relies on open lgic)
spatial summation
several weaker signals from different locations vs temporal several weak signals from one source that add up
facilitation increases quantal content why
the residual calcium hypothesis- ca enters to trigger neurotransmitter release then is removed
when second stimulus arrives soon after the first, new ca enters before the initial pulse is fully removed
this causes smaller synaptic potentials with repetitive stimulation
short term depression
ionotropic receptors
fast, ion channels
metabotropic receptors
slower, ligand gated, can activate a g proteins
g protein coupled receptors steps
1) binding of neurotransmitter to the extracellular receptor protein
2) activation of g proteins
3) activation of effector systems
secondary messengers
the activated proteins are enzymes that generate small molecules (second messengers like cyclic amp)
camp activates protein kinase a (pka) which phosphorylates proteins by adding phosphate groups and changes the properties of the proteins so it can activate other proteins
the 3 general second messenger systems that interact with specific g proteins
increases camp (gs)
decreases camp (gi/go)
stimulates phospholipase c, dag, ip3, pkc
opiate receptors are…
GPCRs and the ligands are small peptides called enkephalins and endorphins
pain modulation by opiate receptors
drg cells sense pain
spinal interneuron releases enkephalin
enkephalin binds GPCR
g protein (go) inhibits VGca channel
less neurotransmitter release when activated (weaker pain signals w opioid receptor activation)
aplysia
giant sea slug that has simple nervous system and large neurons, stereotyped behaviors
habituation
repetitive stimulation leads to decreased response
what does habituation lead to
smaller epsps, decreased quantal content due to short term depression
sensitization
intensified response after harmful stimulus
Synaptic Strength
the average change in membrane potential of a postsynaptic neuron
elicited by a presynaptic action potential
changes in strength or efficacy of neuronal connections. Can be
caused by a variety of physiologic and signaling mechanisms at time scales that vary from ms
to days or longer
Synaptic modulation
Short-term plasticity
a change in synaptic
strength (time scale of milliseconds to
seconds) caused by presynaptic mechanisms
which alter the quantal content (average # of
vesicles released by one presynaptic action
potential
Facilitation
increased synaptic strength
(EPSP amplitude) apparent after two or more
presynaptic action potentials. Caused by
elevation of residual Ca2+ in the presynaptic
termina
Short-term depression
decreased synaptic
strength (EPSP amplitude) apparent after two
or more pre-synaptic action potentials.
Caused by depletion of vesicles from the
presynaptic terminal
Ionotropic receptor
a neurotransmitter-gated ion channel which directly leads to changes in
membrane potential
Metabotropic receptor
a neurotransmitter receptor that effects neuron excitability or
membrane potential indirectly through
intracellular signaling cascades
Neuropeptides
large classification of
neurotransmitter molecules that are
made up of a short polypeptide chain.
Neuropeptides active GPCRs (see
below) for diverse effects on varying
timescales.
G-protein coupled receptor (GPCR)
Type of metabotropic receptor with 7
transmembrane domains that interacts
with G proteins. GPCRs are a diverse
group with each subtype activated by
one of a variety of ligands (light,
specific neuropeptides, sugars, or
lipids)
Second messenger
one of the intracellular signaling molecules that is activated by an
extracellular signal (i.e. activation of GPCR) and triggers a signaling cascade to alter a neuron’s
excitability or physiology
Aplysia
a type of sea slug used as an experimental animal to study the molecular
underpinnings of behavioral learning or plasticity. A relatively simple circuit causes a reflexive
retraction of the gills when the animal’s siphon is touched. This response and the underlying
synaptic strengths can be modulated
Habituation
a decrease in the
magnitude of behavioral responses to
repeated stimuli. In Aplysia, repeated
stimulation of the siphon causes a
reduced gill retraction after multiple
stimulations. This is due in part to a
decrease in the synaptic strength
between the sensory and motor
neurons
Habituation
a decrease in the
magnitude of behavioral responses to
repeated stimuli. In Aplysia, repeated
stimulation of the siphon causes a
reduced gill retraction after multiple
stimulations. This is due in part to a
decrease in the synaptic strength
between the sensory and motor
neurons
Sensitization
an increase in the
magnitude of a behavioral response to a
stimulus after a separate, often noxious
stimulus has been applied. In Aplysia,
pairing a shock to the tail with
stimulation of the siphon, causes a
increase in gill retraction when then
stimulating the siphon alone
Heterosynaptic plasticity
when synaptic strength between two neurons maybe be regulated by a third neuron/synapse. (e.g.
sensitization in Aplysia)
Know the mechanisms underlying synaptic facilitation and short-term depression and be
able to graph the effects of each on EPSPs
Predict how changes in the presynaptic terminal and [Ca2+] affect the magnitude of the
EPSP
Explain the differences between slow and fast synaptic responses, including any
advantages of slow, metabotropic signaling
Diagram how a synapse can be purely modulatory including mechanisms that would either
increase (potentiate) or decrease (depress) a post synaptic response
