Exam 3: Topic 7 Flashcards
plasticity
changes in neuronal function as a result of experience ⇒ prior excitation or inhibition
what does plasticity always require?
intracellular signaling
- Can last from msec to hours and days or longer
how does plasticity interact with the environment inside and outside our bodies?
it allows the environment to change the neuron based on what is happening in it
what can the environment change in neurons? (4)
- Excitability of a neuron
- Ability of the neuron to signal to another neuron ⇒ excite or inhibit
- The number and types of synapses on a neuron
- Morphology of the neuron
homeostasis
the drive for a biological system to try to maintain the certain set point
what are the 4 short term modes of plasticity?
- facilitation
- depression
- augmentation
- potentiation
does facilitation increase or decrease synaptic strength?
increase
does depression increase or decrease synaptic strength?
decrease
does augmentation increase or decrease synaptic strength?
increase
does potentiation increase or decrease synaptic strength?
increase
does habituation increase or decrease synaptic strength?
decrease
does sensitization increase or decrease synaptic strength?
increase
does LTD increase or decrease synaptic strength?
decrease
does LTP increase or decrease synaptic strength?
increase
what is the time frame of facilitation?
msec
what is the time frame of depression?
msec-seconds
what is the time frame of augmentation?
seconds
what is the time frame of potentiation?
minutes
what is the time frame of habituation?
minutes
what is the time frame of sensitization?
minutes-hours
what is the time frame of LTD?
hours-days-beyond
what is the time frame of LTP?
hours-days-beyond
what happens with increase of timescale of mechanistic modulation?
the more complex and diverse the mechanisms are
- Many of the long term mechanisms proceed through the short term pathway first
what is facilitation?
a presynaptic phenomenon due to calcium only observed post synaptically where the amplitude of second potential is higher than first
- Due to intracellular signaling from calcium ⇒ calcium rushes into the cell and interacts with synaptotagmin to release via exocytosis
what happens when a second actin potential occurs shortly after the first in facilitation?
there is still calcium in the presynaptic terminal ⇒ even more calcium in the cell leads to more synaptic vesicles being released leading to an enhancement of the postsynaptic response
- postsynaptic response is much smaller than the presynaptic response (mV)
what happens in synaptic plasticity paired pulse facilitation (PPF)?
if the interval between APs is short and the Ca2+ from the previous AP has not been cleared, then Ca2+ can accumulate at higher concentrations and more synaptotagmin binds Ca2+ and more SVs are released
- the longer the time interval between the first AP and the second AP the less the aptitude of facilitation is
T/F when time interval between AP’s is at 10 ms or less there is a strong facilitation?
True
- But as the interval between the two increases the facilitation gets smaller
- Increase in calcium still but there is cleaning of the calcium with time between AP’s
what makes the difference between depression vs augmentation?
the amount of Ca2+ levels
- normal vs intermediate vs low
what happens with low stimulation to neurons in postsynaptic response?
there is a steady drop off in the postsynaptic response and follows a slow decline
what happens with a high stimulation to neurons in the postsynaptic response with normal calcium levels
there is a strong and fast depression before it recovers again and follows the slow decline of the low stimulation condition ⇒ due to vesicle depletion hypothesis
depression
occurs when the pool of neurotransmitter SVs is depleted
- the postsynaptic response in mV drops to almost 0
what happens to the postsynaptic response with intermediate Ca2+ instead of normal levels with high/low stimulation?
for normal levels without a strong stimulation there is a steady decrease, but with stimulation there is a sharp decrease to 0 which bounces back up to follow the slow decrease line
- for intermediate calcium there are low levels of mV response already with low stimulation and then when high stimulation occurs augmentation happens where there is a fast increase in mV follow by a steady decline back to baseline levels for low stimulation
what happens to the postsynaptic response when you lower the extracellular calcium?
the same stimulus does not deplete the SVs and instead augmentation occurs
Augmentation
a sustained (seconds) elevation in presynaptic terminal calcium ⇒ still calcium coming in but not as much as in depression
- Is not enough to cause max vesicle fusion
what protein modification does augmentation lead to?
Leads to modification of a Ca2+ binding protein (DOC2) that is part of the SV release machinery
what happens to the postsynaptic response in situations of very low calcium when there is low/high stimulation?
there is only augmentation during high frequency stimulation ⇒ likely due to calcium binding to DOC2
- there is a bell shaped increase and decrease that isn’t as drastic as intermediate Ca2+ conditions
T/F Augmentation occurs both in biologically normal conditions and in labs?
False
- don’t see augmentation unless under laboratory conditions ⇒ depleted extracellular calcium
what does DOC2 do?
required for superpriming in augmentation
- DOC2 and munc13 form a complex
- Some of the vesicles are superprimed and these complexes will bind to the vesicles that are superprimed
- if the cell has a stimuli from AP’s, then the protein complex will bind and increase the number of super primed vesicles for fusion
what does super priming refer to?
Heightened probability the vesicle will release compared to the other vesicles
what does super priming result in?
more vesicles fusing and more postsynaptic release occurs
potentiation
increase in mV due to presynaptic changes but the postsynaptic response lasts minutes
why does potentiation take minutes to return to normal levels?
Elevation in intracellular calcium activate protein kinases that phosphorylate proteins in vesicle release promoting synaptic activity
- Potentiation can therefore last longer than the rise and clearing of intracellular calcium
- after high freq stimulation when you go to low stim again there is a high postsynaptic increase in response which comes back down over minutes
what is the general pathway for potentiation?
Ca2+ levels activate protein kinases which phosphorylates the K+ channels and decreases their efficiency
what are the advantages to using aplysia (sea slug) for testing? (4)
- Total nervous system ~20,000 neurons (simple system)
- Many neurons are large and easy to record from
- Across animals, the same neuron is easily identified
- Limited behaviors
what phenomenon did we learn from Aplysia?
habituation and sensitization
how does habituation work with aplasia?
if you touch the siphon, there is a strong and fast contraction that lasts for a period of time in seconds before it relaxes
- If you repeatedly touch this within an interval, as long as the tissue is not being damages the neurons will begin to have less gill contraction ⇒ doesn’t stay up as long
- Eventually there is little to no response from the gill
how does sensitization work with aplysia?
If you electrically shock the tail or pinch it with forceps and touch the siphon after, the next sensitization has a strong and prolonged gill contraction
how does the neuroanatomy wiring of the aplysia work?
- the skin is innervated by multiple sensory neurons which project into the nervous system (siphon neuron innervates the interneuron and the motor neuron directly
- the tail pathway innervates a modulatory neuron before the interneuron synapses on the main sensory neuron at both locations - Excitatory interneuron
- Motor neuron
- This synapses onto muscles in the gill and causes the gill contraction
which nerves are involved in habituation only of aplysia?
- siphon skin and sensory neuron
- motor neuron and gill
which nerves are involved in sensitization only of aplysia?
- tail and sensory neuron
- modulatory neuron
how does aplysia sensitization mechanically work?
the modulation from the sensory neuron innervating the siphon will enhance the release on the interneuron to sensitize the response of the gill withdrawal reflex by over-activating the motor neuron
what happens to the EPSPs with habituation and sensitization?
EPSPs will decrease even with the same stimulus and action potential but then increase to higher than prior levels for sensitization
what has to decrease for habituation to occur? Where does this happen?
neurotransmitter release; between the sensory neuron and the motor neuron
what neurotransmitter is release during habituation vs sensitization?
during habituation glutamate is mostly released from the sensory neuron but with the tail shock serotonin is released on to the sensory neuron from the interneuron => more NT is released from the sensory neuron on the motor neuron with sensitization
what happens when serotonin is released to the siphon sensory neuron?
GPCR-Gs activation stimulates adenylyl cyclase to make cAMP which activates PKA to phosphorylate things
what two things does PKA phosphorylate?
these two conditions extend duration of the AP and enhances neurotransmitter release
1. VGK+ channels and reduce channel activity
2. VGCa2+ channels and increase channel activity to release NT on the motor neuron
what receptors are activated on motor neurons after PKA is activated?
glutamate
what 2 ways do catalytic subunits get activated longterm?
- PKA itself can translocate and phosphorylate a protein called CREB ⇒ production of ubiquitin hydrolase which keeps catalytic subunits on for activity
- C/EBP pathway via unidentified kinases lead to synaptic growth
what happens after C/EBP is activated?
there is more branching in synaptic cites which causes functional and structural change
who was patient H.M?
man where doctors removed hippocampi(s) because he had severe epileptic seizures in an isolated area
- Memories from > 3 years before are okay
- Memories from < 3 years before are partially lost, most loss from time closer to surgery
retrograde amnesia; anterograde amnesia
cannot recall previous memories; cannot make new memories
what are the scientific conclusions from patient H.M’s case? (2)
- Old and new memories are stored in different brain regions
- New memories are formed in the hippocampus
declarative memories
explicit and can be recalled for knowledge of things, places, etc.
- episodic and semantic
- Spacial
- Associative
- Recognition
episodic memories
personal experiences
semantic memories
factual details
what brain structure forms memories and what brain structure likely stores them?
hippocampus forms and stores shorter term memories while prefrontal cortex stores longterm memories
procedural memory
implicit skills retained after learning
what brain regions are involved in procedural memory? (4)
Striatum, cerebellum, cortex, limbic system are all involved
what is the wiring pathway of the hippocampus
- Input comes in through the perforant path onto granule cells (dentate gyrus area)
- Granule cells project to the CA3 region where cell bodies are
- Schaffer collaterals: CA3 pyramidal cell axons project and synapse onto CA1
where does LTP occur in mammals?
in the Shaffer collaterals
what are EPSPs like for the primary and secondary pathways of Shaffer collaterals that synapse on another neuron in vitro?
baseline EPSP in CA1 neuron is stable over time (-10-0 min) when stimulating Schaffer collaterals at a low frequency
- the primary pathway increases a lot in EPSPs after a high frequency stimulation and slowly decreases (not reaching zero)
- the secondary pathway does not increase and stays at baseline
what happens if you do the EPSP stimulation experiment with a primary pathway in vivo?
the increase remains following the return to baseline stipulation up to 1 year for the primary pathway
- when we inorganically stimulate the state to be way too high, there is a robust effect ⇒ the cells typically do not do this
what are the 3 properties of LTP?
- Coincident activity
- Specificity
- Association
coincident activity
activity is required in both the presynaptic and postsynaptic neurons
- two things need to happen in a short time frame to be a coincidental activity
what happens with a strong depolarizing pulse in LTP?
EPSP mV will increase and stay high for a long period of time (minutes or more)
- a coincidence detector is required for LTP
what 2 things are needed for coincidence?
- Activity in presynaptic cell
- Depolarization in the postsynaptic cell shortly after
specificity
different pyramidal neurons synapsing onto the same cell but specific for which pathway is active
- When pathway 1 is stimulated the synapse is strengthened but the pathway 2 synapse is not strengthened
T/F only the active pathway synapse is strengthened?
True
- pathways 1 and 2 are different Ca3 neurons that synapse on the same postsynaptic CA1 neuron
- Pathway 1 received high frequency stimulus
- Pathway 2 is not stimulated
associativity
the two synapses will occur and be strengthened with one another when a strong stimulation occurs
how does the process of association work if a high stimulus is given to the primary pathway and a low stimulus is given to a secondary pathway in association?
with high frequency stimulation to synapse 1 and weak stimulation to synapse 2 (typically no AP) relatively at the same time then both the synapses will be strengthened
- always get potentiation with strongly associated pathway
- synapses whose activity is associated in time will undergo LTP, even if they don’t all receive the tetanic stimulus
Hebbian plasticity
an increase in the strength of connections between neurons whose activity is correlated produces memories.
- cells that fire together wire together
- you need both specificity and associativity for this
- this changes the firing pattern of the postsynaptic neuron and there are losses of synapses with unrelated output patterns
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