Lecture 9 - Chapter 8: Synaptic plasticity Flashcards
Name examples of:
- Immediate memory
- Working memory
- Long-term memory
- Immediate memory → someone says the number 9 and you immediately store this memory for a couple of seconds.
- Working memory → keeping information for a short period of time, for instance when you lost your key around the house and are looking for it (you don’t remember this for the rest of your life)
- Long-term memory → can be reached when rehearsal takes place.
What’s the importance of synaptic plasticity?
It’s important for remembering and memory
What is short-term plasticity?
Short term plasticity is short term communication between neurons through synapses, which is triggered by the release of calcium (facilitation) and results in the release of neurotransmitters.
The fact that calcium levels instantly rise, but do not instantly decay, gives rise to plasticity (augmentation and potentiation).
What is long-term plasticity?
This is plasticity that lasts for more than 30 minutes. This is dependent on NMDA receptor-dependent calcium influx. Calcium changes the properties of synapses (post-translational modifications), which also affects gene expression and protein synthesis.
There are three different forms of short-term plasticity. Name and explain these.
- Facilitation → enhances synaptic transmission for tens of milliseconds.
- Augmentation → enhances synaptic transmission for a few seconds.
- Potentiation → enhances synaptic transmission for tens of seconds to minutes.
What is paired-pulse facilitation?
Here, postsynaptic potentials evoked by an impulse are increased when that impulse closely follows a prior impulse. This is due to the fact that during short-term plasticity, there’s instant rise of calcium and slow decay. So when the second impulse closely follows the first impulse, there’s still residual calcium that can enhance the second postsynaptic potential.
So when does paired-pulse facilitation decay?
When the intervals between stimuli increase.
What’s the opposite of faciliation?
Short-term depression
What happens during short-term depression and how does it occur?
Short-term depression decreases the amplitude of postsynaptic potentials. It is a result of the decrease in ready releasable pools of vesicles as a result of frequent stimulation.
What is seen during stimulation?
That it is an interplay between facilitation and depression (will become more clear in the following questions).
What happens when there’s high frequency stimulation in the following situations:
- Normal [Ca2+]
- Low [Ca2+]
- Intermediate [Ca2+]
- High frequency stimulation in normal [Ca2+] concentrations leads to synaptic depression, due to the release of almost all readily releasable pools.
- High frequency stimulation in low [Ca2+] concentrations leads to synaptic augmentation. This is because, there’s not enough calcium to release/deplete all the readily releasable pools.
- High frequency stimulation in intermediate [Ca2+] concentrations leads to both synaptic augmentation as depression. This happens, because there’s enough Ca2+ to stimulate the secretion of readily releasable pools, but this eventually will lead to the depletion of the pools (only less rapid compared to a normal [Ca2+] concentration.
Summarizing the previous questions:
Explain what happens during short-term plasticity upon stimulation.
Stimulation starts with paired-pulse facilitation (augmentation), which increases the postsynaptic membrane potential. At some point, the readily releasable pools are depleted. This leads to depression.
When the stimulation ends, there is still residual calcium available in the synaptic cleft (due to slow decay). This ultimately leads to post-tetanic potentiation.
Researchers won the Nobel prize for a certain experiment they performed in the gill of Aplysia. What was researched?
The gill of Aplysia has a withdrawal reflex. So if the siphon was touched, it pulled back/contracted its gill. So they started performing experiments on Aplysia to see what would happen to the magnitude of gill contraction when the siphon was touched in multiple trials.
What did they see during the experiment of Aplysia and the magnitide of gill contraction after touch?
That in the first trial where they touched the siphon, they still measured a high amplitude of gill contraction. But after a few trials (> trial 6) the magnitude of gill contraction began to decrease. At trial 13, there was almost no magnitude of gill contraction measured. So habituation occurred.
What happens to the amplitude of gill contraction after giving a shock to the tail of the Aplysia and simultaneously touching the siphon?
Sensitization occurs, which is the progressive amplification of a response due to (repeated) administration of a stimulus.
What’s seen here?
Short-term memory.
- You see that when the stimulus (touching siphon) is given several times, the amount of response to the stimulus decreases (black lines).
- You see that when a single tail shock is given, the response to this stimulus first increases (habituation). But if you repeat this several times, also the response to the tail shock will decrease again (sensitization).
How do you go from short-term sensitization/memory to long-term sensitization?
By shocking the tail repeated times for several days, as can be seen in the picture.
Describe what happens in the neurons of Aplysia during short term sensitization.
Touching the siphon skin activates a sensory neuron. This neuron releases glutamate onto a motor neuron. The motor neuron release acetylcholine to the muscle of the gill, which leads to contraction of the gill.
What happens when there’s habituation of the neuronal system responable for the contraction of the gill in response to frequent stimulation by touch?
There’s less response to the stimuli, therefore the sensory neuron sents less signals to the motor neuron and the amplitude of contraction is decreased.
Describe what happens when the tail of Aplysia is stimulated with a shock.
The tail is connected to a sensory neuron. This neuron is connected to a modulatory interneuron, that has connection with the sensory neuron of the siphon skin and the motor neuron that is connected to the gill.
When the tail is stimulated, signals are sent through the sensory neuron to the modulatory interneuron. Unlike most interneurons, this modulatory interneuron is excitatory and excites the interneuron and motor neuron that have been habituated by touching the siphon skin.
To summarize:
What neurotransmitters are produced by the modulatory interneuron, sensory neuron and motor neuron?
- Interneuron → serotonin
- Sensory neuron → glutamate
- Motor neuron → acetylcholine
Describe what happens inside (referring to intracellular signal cascades) the neurons of Aplysia during short term sensitization.
- Stimulating the tail Aplysia with shock
- Sensory neuron produces glutamate
- Glutamate activates modulatory interneuron
- Interneuron produces serotonin
- Serotonin receptor activation on sensory neuron
- Production of cAMP, activation of PKA
- Reduces K+ channel activation
- AP mediated effect prolonged
- Increased Ca2+ influx
- Enhanced glutamate release from sensory neuron → enhanced motor neuron activation → enhanced ACh release
- Enhanced gill contraction
What does short-term sensitization depend on and what does long-term sensitization depend on?
- Short-term sensitization → PKA-dependent enhancement
- Long-term sensitization → CREB-dependent gene expression
Describe what happens inside (referring to intracellular signal cascades) the neurons of Aplysia during long-term sensitization.
- Stimulating the tail Aplysia with shock
- Sensory neuron produces glutamate
- Glutamate activates modulatory interneuron
- Interneuron produces serotonin
- Serotonin receptor activation on sensory neuron
- Production of cAMP, activation of PKA
- PKA activates CREB
- CREB increases gene transcription
- Transcription of ubiquitin hydrolase further activates PKA
- CREB also activates C/EBP → C/EBP activates genes responsible for adding more synapses.