PSYC 310 Lecture Notes - Lecture 15: Cre Recombinase, Motor Neuron, Protein Synthesis Inhibitor
7 May 2018
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Synaptic tagging and allocation
PSYC 318
21 March 2018
• Learning objectives
o Synaptic tagging
▪ What is a tag? What is a plasticity-related protein PPP?
▪ What is behavioral tagging?
▪ Relationship between tagging and serial vs. parallel memory traces
o Allocation
▪ How do we know if neuron is allocated to memory trace
▪ Neuronal excitability
▪ Necessary vs. sufficient or ability of overexpression of CREB to increase
probability of allocation
• What is difference between necessary vs sufficient
• A requirement for gene expression: implications for memory
o Gene expression made easier allows memories to be formed
o Decision to encode memories for long-term is not just synaptic-activation but a
cell-wide decision to activate gene expression
o Nucleus is in the middle of the cell not close to any synapse and that’s the only
place gene expression can happen
o We believe specific synapses are modified to underlie neuronal memory
▪ Extracting of neuronal principles underlying majority of AI uses this as a
founding idea: units connected by synaptic weights that independently
change
▪ It is important that synapses can be modified differentially
▪ Our understanding is how long-term memories can be encoded
• Synaptic tagging
o Product of gene expression (nuclear stuff) sent out everywhere
o Only when these two mix, only when you have both nuclear stuff and tha tag, that
you end up with a strengthened synapse
o You need 2 things to generate long-term change in synaptic strength: tag and
product of gene expression
• Synaptic tagging in aplysia system
o Tagging works from both pre and post synaptic sides of synapse
• A model for synaptic tagging in aplysia cultured sensory to motor neuron synapses
o A1 is sufficient to give you a long-term increase in synaptic strength
▪ Lasting for 3 days
o A2 no changes in the other synapse
o B1 summary of changes in synaptic strength at 24 and 72 hours
o B2 looks at change in the number of synapses between pre and post synaptic
neurons
• Synapse-specific facilitation
o This still requires transcription
o If you block CREB you don’t get long-term facilitation, still requires gene
expression in nucleus
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o Limited to synapses that serotonin is in
o Transcriptional products mRNAs and sent to both sides of the synapse, so the
difference is not the export of mRNAs between one synaptic site and the other,
maybe differences in translation
• Capture in synaptic tagging
o These previous experiments don’t illustrate capture
o When you add 5HT to synapse there were a # of things that had to happen
▪ Gene expression had to be activated, 5HT had to active something at
synapse that made a tag at the synapse
▪ These are confounded: you need both of these to happen
▪ You can dissociate the two in a capture experiment by activating gene
expression and use other synapse to determine what is made to capture
products of gene expression
• Adding 5x serotonin at one synapse but add 1 application of 5HT at the other synapse
o Sufficient to give short-term but not long-term facilitation
o Is is sufficient to make a tag?
o Yes
o Difference between experiments is that both synapses show LT facilitation
o Only tagged synapse shows increase in synaptic strength and vericocity (?)
• You need activation of gene expression and tag
o Application of 5HT was not sufficient to activate gene expression btu was
sufficient to generate the tag
• One application of 5HT is sufficient for capture
• LTF just requires tag and gene expression
o Other things required for interaction
o Want to do experiment to specifically show that it was just gene expression and
tag
o Replace applications of 5HT with just injection of phosphorylated CREB in-vitro
into nucleus of cell
o They had to inject phosphorylated CREB, because of what phosphorylation of
CREB does to activate it (to be talked about in later lecture)
o When they do this experiment again in C2 sufficient to give long-lasting increase
in synaptic strength lasting 72 hours and nothing happens at other un-tagged
synapse
▪ If you look 12 hours after experiment there is no LTF, but there is STF
because you added serotonin to synapse
▪ All of a sudden LTF comes up later
▪ Argument that this is a parallel pathway, that STF doesn’t last as long as
tag does, and for tag to interact as a product of gene expression it takes a
while for that to be translated into increase of synaptic strength
▪ LTF requires gene expression in synaptic tag but not necessarily anything
to do with what underlies STM
• How long does the tag last?
o Experiment: dissociated when you add the tagging stimulus
o Separate in time the activation of gene expression and formation of tag
find more resources at oneclass.com
find more resources at oneclass.com
