Activity-Dependent Synaptic Plasticity

Transcript

0:00 – 0:30  [Basic Definition]  Activity-dependent plasticity is a change in the strength of synaptic transmission that is caused by previous synaptic activity.  Activity-dependent synaptic plasticity can relate to changes in the presynaptic neuron – for example, a change in the amount of neurotransmitter released in response to each presynaptic action potential.  Activity-dependent synaptic plasticity can also relate to changes in the postsynaptic neuron – for example, a change in the number of neurotransmitter receptors on the membrane of the post-synaptic cell.

0:30-2:30 

Changes in the strength of synaptic transmission or plasticity can occur on both sides of the synapse, either by manipulating the probability of presynaptic release or the responsiveness of postsynaptic receptors. For instance, the calcium-dependent nature of neurotransmitter release leads to short term plasticity in synaptic transmission. The accumulation of calcium following multiple spikes can lead to more effective vesicle fusion and thus facilitate neurotransmitter release and the activation of post-synaptic receptors. On the other hand, the reliance on readily releasable pools of vesicles for neurotransmission means that as activity levels persist and vesicles are depleted, neurotransmitter release is depressed.

While these are examples of short term synaptic plasticity on the pre-synaptic side, there are also examples of longer term plasticity on the post-synaptic side. Strong electrical stimulation of presynaptic axon terminals from one input leads to long-term potentiation of synaptic transmission, measured as an increase in the amplitude of the excitatory post-synaptic potential or EPSP connecting the two neurons. Critically, long-term potentiation or LTP is synapse specific and limited to the inputs that underwent stimulation, perhaps mimicking formation of a specific memory.

However, synapses do not just get stronger. Interestingly, weak electrical stimulation has exactly the opposite effect, leading to long-term depression of synaptic transmission, known as LTD. Again, the changes are synapse specific, perhaps mimicking the selective loss of information.

Calcium entry through the ionotropic NMDA-type glutamate receptor is linked to the post-synaptic changes underlying LTP. Activation of PKC phosphorylates ionotropic AMPA-type glutamate receptors leading to a greater conductance and larger EPSPs. In addition, activation of CaMKII mobilizes new AMPA receptors from local vesicular organelles, which also increases EPSP amplitude.

Differences in the levels of NMDA activation have also been linked to LTD. During strong stimulation, higher levels of NMDA activation lead to greater calcium entry, promoting activation of protein kinases that trigger LTP, as above. However, during weaker stimulation lower levels of NMDA activation lead to less calcium entry, promoting the activation of protein phosphatases that trigger the opposite response in LTD.

2:30-3:00  [Parallel Vocabulary] In introductory classes you learned about activity-dependent synaptic plasticity.  But Neuroscience is an interdisciplinary field, so there are many words for this term – For example, you may also hear about neuroplasticity, or just plasticity, and these terms relate more broadly to any change in neural organization.  Activity dependent synaptic plasticity is an umbrella term that refers specifically to changes at a synapse and these include increases in synaptic strength such as facilitation, augmentation, and potentiation, as well as decreases in synaptic strength such as depression.

3:00-4:00  [Here’s a real world example]  Activity dependent synaptic plasticity plays an important role in learning and memory.  For example, did you know that some types of learning require activity dependent synaptic plasticity in specific parts of the brain?  Fear conditioning, which requires activity dependent synaptic plasticity in the amygdala, is a process that occurs when a neutral stimulus like a sound or a light is repeatedly presented at the same time as a naturally avoided stimulus like a painful shock – eventually a test subject learns to fear the previously neutral stimulus.  Experiments in rats have shown fear conditioning requires long-term potentiation (which is abbreviated LTP) in the amygdala.  Recall that LTP is a form of activity dependent synaptic plasticity that involves increasing the strength of synaptic transmission by inserting AMPA receptors into the membrane of the postsynaptic neuron – when this  process is selectively blocked in the amygdala, fear conditioning does not occur and a rat fails to fear a neutral stimulus, even after that stimulus is repeatedly paired with a painful experience.

4:00-6:00 [Follow along with this example]

6:00-6:30 [Here are a few readings to help you review]
1) Neuroscience Exploring the Brain (Bear)

• Chapter 25: “Molecular Mechanisms of Learning and Memory”.

2) Principles of Human Physiology (Stanfield)

• Chapter 8: “Synaptic Plasticity”

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