Synaptic Plasticity: Module 2.8 - 2.9 Flashcards
What does synaptic plasticity mean?
The plasticity of synapses refers to the ability of synaptic connections between neurons to change in strength, efficiency, or structure over time. This adaptability is crucial for learning, memory, and the overall function of the brain. Synaptic plasticity allows the nervous system to respond dynamically to new information, experiences, or injuries.
Define Synaptic Strength.
The mean amplitude of the postsynaptic response.
Can depend on the previous activity of many synapses.
What are the two types of memory?
Working Memory(lasts seconds): Is the continual series of fleeting memories that we use during the course of a day to remember facts and events. ie: what was just spoken to use, where we put the phone down, whether we are coming or going, things that are useful for the moment but need not be stored for longer.
Is thought to depend on persistent neural firing.
Long-Term Memory (may lasts for hours to decades, and strongly resist disruption and replacement): Allows the accumulation of knowledge over a lifetime.
It is thought to depend on persistent neural firing but rather involve long-lasting changes in the strength of synaptic conncections - More results structural changes of synapse.
Some memories formed after single event and some with repitition.
Explain the dual packaging scheme of neurotransmitters.
Small Transmitters packaged into small vesivles closer to membrane.
Larger Neuropeptides in larger vesicles further away from membrane.
This scheme allows the neuron some control over the relative release of the two types of NT.
Repeated synaptic activity briefly increases or decreases strength
What are the 3 types of High Freq Stimulation?
Facilitation: lasts 10-100s of msec - Each pulse enhances AP on a narrow time scale until plateua.
Potentiation: lasting sec. to several min. and outlasting the period of high frequency stimulation. - Outlasts stimulus - After stimulus ends you still have activity.
Depression: short term decreases - can occur diring high-frequency stimulation. - Weakened synapse that goes back to normal.
Repeated synaptic activity briefly increases or decreases strength
What is the 1 type of Low Freq stimulation?
Habituation: a slowly progressing decrease - *overall reduced strength and response - lasts a long time. *
What are some reasons of short term increases in synaptic strength?
1) The presynaptic terminal may release more transmitter for each action potential.
2) The postsynaptic receptors may be more responsibe to transmutter because of a change in their number or sensitivity.
Can be both at same time
What is the reason for short term decrease in synaptic strength (habituation)?
Due to fewer transmitter quanta release per action potential.
Depends on number of vesicles of NT available
What experiment was used to show Habituation.
Gill Withdrawal Reflex Circuit
What experiment was used to demonstrate sensitization.
Aplysia Tail Shock
What is the mechanism of short-term sensitization?
The serotonergic interneurons
(facilitating interneuron) form
synapses on many regions of the
sensory neurons, including axo-
axonic synapses on the presynaptic
terminals of the sensory cells.
After a single tail shock, serotonin is
released from the interneurons and
binds to GPCR (s). This leads to PKA
activation. PKA phosphorylates a K+
channel, causing it to close. This
broadens the action potential and thus
enhances the duration of Ca2+ influx
through Cav channels, which in turn
enhances transmitter release.
Serotonin also activates a second type
of GPCR (q), leading to the activation
of PKC. PKC phosphorylation enhances
the functioning of the release
machinery.
What is the mechanism of long term sensitization?
Key Steps and Pathways:
Pathway 1: PKA Translocation to the Nucleus
Repeated tail shocks elevate cAMP levels persistently, which activates PKA.
PKA catalytic subunits move into the nucleus and phosphorylate a transcriptional activator called cAMP response element-binding protein 1 (CREB-1).
Pathway 2: Activation of CREB-1
Phosphorylated CREB-1 binds to cAMP response elements (CRE) in the DNA, located upstream of cAMP-responsive genes.
This binding initiates gene transcription, leading to the production of proteins necessary for long-term changes.
Pathway 3: MAPK Activation and CREB-2 Inhibition
PKA also activates mitogen-activated protein kinase (MAPK), which phosphorylates and inhibits CREB-2, a transcriptional repressor.
This removal of CREB-2’s inhibitory action further promotes the transcription of CREB-1-regulated genes.
Pathway 4: Ubiquitin Hydrolase and Persistent PKA Activation
One gene activated by CREB-1 encodes ubiquitin hydrolase, a component of the proteasome system.
Ubiquitin hydrolase degrades the regulatory subunits of PKA, maintaining the catalytic subunits in their active state. This allows PKA to remain persistently active even after cAMP levels return to baseline.
Pathway 5: C/EBP and Growth of New Synapses
CREB-1 also activates transcription of C/EBP (CAAT/enhancer-binding protein), a transcription factor involved in long-term structural changes.
Proteins expressed under C/EBP’s regulation promote the growth of new synaptic connections, solidifying the long-term sensitization.
How do you produce sensitization for a day and a week?
- 5 training session or repeated application of serotonin over approx 1 hour produce long term sensitization lasting >1 day.
- Training over several days produce sensitization for >1 week.
What is consolidation?
Conversion of short-term memory into long term memory.
Requires synthesis of messenger RNAs and proteins.
What is an important part of the brain for learning and memory?
Hippocampus
What are the 3 pathways/regions of the hippocampus?
What is Cooperativity or Associative LTP.
There is Stong inhibition in the hippocampus that causes weak synapses.
NEED simultanious cooperative presynaptic activation to activate the post synapting neuron for LTP.
Stimuli that are related will cooperate to intiate LTP repsonse.
Describe LTP at the Schaffer Collateral Pathway.
Theta Burst Stimulation (TBS) at the CA3 Neuron induces LTP and increases EPSP in CA1. - Requires NMDA receptors for LTP.
Receptor Antagonist prevents LTP by blocing NMDA Receptors.
What is early LTP and what are its 2 mechanisms?
Early LTP: Lasts 1-3 hours and does not require new protein syntheses, cAMP or PKA activation.
2 Mechanisms
Induction: More NT release - Large depolarization removes Mg block; retrograde signal(Nitric Oxide?) can increase NT release
Expression: Addition of New Ampa receptors through PKC pathway. (Ampafication)
What is late LTP and what are its mechanisms?
Late: four or more trains of synaptic stimulation induce a late LTP lasting up to 24 hours. IT does require cAMP and PKA, as well as changes in gene transcription and the synthesis of new proteins (long lasting due to structural changes)
New Synaptic Connection: Repeated Potentials —> Ca influx —> Recruits Adenyl Cyclase —> Generates cAMP —> activates PKA —-> Activates MAP Kinase —> goes to nucleus and phosphorylates CREB 1 —> Activates CRE Promoter –> Leads to growth of new synapses.
Long Lasting Increase of AMPA receptors: Repeated Potentials activates translation of PKMC (isoform of PKC) –> Leads to long lasting increase of AMPA receptors.
What are the different parts of NMDARs and what do they respond to?
NR1 - Responds to Glycine - Short Tail
NR2A, NR2B - Responds to Glutamate - Long Tail
Explain the Long-Term Depression mechanism?
Low Frequency stimulation produces a modest EPSP and is less effective at relieving the Mg2+ block of NMDA receptors.
Increase in postsynaptic intracellular Ca is much less than in LTP. This is insufficient to activate CaMKII.
**LTD results from the acivation of Ca-Dependent Phosphatase. **
Low Freq Stimulation can cause reduction of Postsynaptic AMPA receptors.
Explain how Phosphorylation and Dephosphorylation affects LTP and LTD.
LTP: Activation of NMDA of AMPA receptors.
High levels of [Ca2+]i -produced by
high-frequency stimulation-lead to a
net activation of protein kinases and
thus phosphorylation of one or more
synaptic proteins that regulate
synaptic strength. One hypothetical
pathway phosphorylation modulates
synaptic proteins, such as AMPA
receptor channel. The postsynaptic
neuron also seems to be able to
stimulate the presynaptic terminal.
LTD: A moderate increase in [Ca2+]i -
produced by low-frequency
stimulation activates phosphatases,
which presumably dephosphorylate
the same synaptic proteins as in the
previous example.
