Summary
It is shown that long-term potentiation (LTP) is the cellular basis of memory formation. However, since all but small fraction of memories are forgotten, LTP has been further divided into early LTP (e-LTP), the mechanism by which short-term memories are formed, and a more stable late LTP (L-LTP), by which long-term memories are formed. Remarkably, it has been shown that an e-LTP can be stabilized if it is preceded or followed by heterosynaptic L-LTP.
According to Synaptic Tagging and Capture (STC) hypothesis, e-LTP is stabilized by capturing proteins that are made by L-LTP induction. The model proposes that this mechanism underlies the formation of late associative memory, where the stability of a memory is not only defined by the stimuli that induce the change but also by events happening before and after these stimuli. As such, the model explicitly predicts that a short-term memory can be stabilized by inducing heterosynaptic L-LTP.
In this grant, I will put this hypothesis into test. Specifically, I will test two explicit predictions of STC model: 1) A naturally formed short-term memory can be stabilized by induction of heterosynaptic L-LTP. 2) This stabilization is caused by the protein synthesis feature of L-LTP. To do this, using optogenetics, I will engineer a short-term memory in auditory fear circuit, in which an animal transiently associates a foot shock to a tone. Subsequently, I will examine if optogenetic delivery of L-LTP to the visual inputs converging on the same population of neurons in the amygdala will stabilize the short-term tone fear memory.
To be able to engineer natural memory by manipulating synaptic plasticity I will develop two systems: 1) A two-color optical activation system which permits selective manipulation of distinct neuronal populations with precise temporal and spatial resolution; 2) An inducible and activity-dependent expression system by which those neurons that are activated by a natural stimulus will be optically tagged.
According to Synaptic Tagging and Capture (STC) hypothesis, e-LTP is stabilized by capturing proteins that are made by L-LTP induction. The model proposes that this mechanism underlies the formation of late associative memory, where the stability of a memory is not only defined by the stimuli that induce the change but also by events happening before and after these stimuli. As such, the model explicitly predicts that a short-term memory can be stabilized by inducing heterosynaptic L-LTP.
In this grant, I will put this hypothesis into test. Specifically, I will test two explicit predictions of STC model: 1) A naturally formed short-term memory can be stabilized by induction of heterosynaptic L-LTP. 2) This stabilization is caused by the protein synthesis feature of L-LTP. To do this, using optogenetics, I will engineer a short-term memory in auditory fear circuit, in which an animal transiently associates a foot shock to a tone. Subsequently, I will examine if optogenetic delivery of L-LTP to the visual inputs converging on the same population of neurons in the amygdala will stabilize the short-term tone fear memory.
To be able to engineer natural memory by manipulating synaptic plasticity I will develop two systems: 1) A two-color optical activation system which permits selective manipulation of distinct neuronal populations with precise temporal and spatial resolution; 2) An inducible and activity-dependent expression system by which those neurons that are activated by a natural stimulus will be optically tagged.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/679714 |
| Start date: | 01-04-2016 |
| End date: | 31-03-2022 |
| Total budget - Public funding: | 1 500 000,00 Euro - 1 500 000,00 Euro |
Cordis data
Original description
It is shown that long-term potentiation (LTP) is the cellular basis of memory formation. However, since all but small fraction of memories are forgotten, LTP has been further divided into early LTP (e-LTP), the mechanism by which short-term memories are formed, and a more stable late LTP (L-LTP), by which long-term memories are formed. Remarkably, it has been shown that an e-LTP can be stabilized if it is preceded or followed by heterosynaptic L-LTP.According to Synaptic Tagging and Capture (STC) hypothesis, e-LTP is stabilized by capturing proteins that are made by L-LTP induction. The model proposes that this mechanism underlies the formation of late associative memory, where the stability of a memory is not only defined by the stimuli that induce the change but also by events happening before and after these stimuli. As such, the model explicitly predicts that a short-term memory can be stabilized by inducing heterosynaptic L-LTP.
In this grant, I will put this hypothesis into test. Specifically, I will test two explicit predictions of STC model: 1) A naturally formed short-term memory can be stabilized by induction of heterosynaptic L-LTP. 2) This stabilization is caused by the protein synthesis feature of L-LTP. To do this, using optogenetics, I will engineer a short-term memory in auditory fear circuit, in which an animal transiently associates a foot shock to a tone. Subsequently, I will examine if optogenetic delivery of L-LTP to the visual inputs converging on the same population of neurons in the amygdala will stabilize the short-term tone fear memory.
To be able to engineer natural memory by manipulating synaptic plasticity I will develop two systems: 1) A two-color optical activation system which permits selective manipulation of distinct neuronal populations with precise temporal and spatial resolution; 2) An inducible and activity-dependent expression system by which those neurons that are activated by a natural stimulus will be optically tagged.
Status
TERMINATEDCall topic
ERC-StG-2015Update Date
27-04-2024
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