PSYC 310 Lecture Notes - Lecture 10: Tactical Airborne Reconnaissance Pod System, Long-Term Potentiation, Gene Expression
7 May 2018
School
Department
Course
Professor
PSYC 318: Monday March 26th, 2018
Associative Memories: LTP
• Learning objectives
o Associative learning: LTP and LTD
▪ What are associative molecules underlying associative memory (NMDARs)
▪ How is Q regulated?
▪ AMPAR receptor trafficking related to how Q is regulated
o Late-LTP vs Early-LTP
▪ Role of GluaA1
• Associative memories
o Pairing of CS and US and leads to response of CS alone
o US leads to response, pairing leads to response in CS alone
o A number of models of associative memory, almost all have US as a shock to the
animals (noxious stimulus)
▪ Diff conditioned stimuli
▪ Tone: auditory fear conditioning
▪ Contextual fear conditioning (when animal pairs a box with being afraid, for
example)
▪ Eyeblink conditioning (in later lecture: to a tone, no shock, puff to eye)
o Normally, animal doesn’t respond to tone, eyepuff, but after conditioning it now responds
and it is related to expectation that the US is going to happen
▪ Animal learns an association
o Weak connection between neurons encoding CS and response neurons
▪ US leads to depolarization of response neurons
▪ Pairing of CS and US leads to a strengthening of connection between neurons
encoding CS and response neurons
• Cause fear, eyes to close, etc.
• Simultaneously, one predicts the other
• CS strength sufficient to cause a response on its own
o This idea is what Donald Hebb was famous for
▪ Psychology professor at McGill
▪ When presynaptic neuron participates in firing of postsynaptic neuron, strength of
connection should increase
▪ Something has to sense the fact that presynaptic neuron participated in firing of
postsynaptic neuron
• Molecular communication that happens when this association happens
o There are many different molecules that have been proposed to be associative molecules
important for sensing associative conditioning
• Associative molecules
o Associative molecule can sense pairing of CS and US
o Adeline cyclase thought to play a role in this
▪ Activated by calcium: if neuron fires before shock
▪ NMDA receptor pairs depolarization of post-synaptic cell US with glutamate
release of presynaptic cell
▪ PKC pairs depolarization of post-synaptic cell with glutamate release of
presynaptic cell (CS) activation of second messenger for PKC
o Pairing activation of cell (pre for aplysia post for other two conditions) with release of
neurotransmitter, G-protein coupled receptor, ligand gated ion channel
▪ Association allows these associaitons to take place
• Long term potentiation (LTP)
find more resources at oneclass.com
find more resources at oneclass.com
o Cellular model of synaptic plasticity
o Occurs in vertebrate brain
o Associative like Hebb’s rules
▪ Rewires firing presynaptic cell, release glutamate, depolarization of postsynaptic
cell
▪ Activate NMDARs to let calcium come in
▪ Calcium signals that the association has taken place
o Synapse-specific
o Potentiation vs. facilitation
▪ In rodents/vertebrates: LTP
▪ Initial mechanisms for LTP and LTF show some differences at one point, but now
words have been used for any broad long-term change in neurons
▪ LTF in aplysia
▪ Originally had mechanistic interpretation based on the roles
• LTP
o Stable over time
o At some point given high-freq stimulation: fire a bunch of APs at once
o Point is to give enough APs so postsynaptic cell becomes depolarized, starts firing APs
itself
o Increase in synaptic strengths which is maintained
▪ Called long-term potentiation
▪ Esp. when maintained for a period of time
o If you only give high frequency stimulation to just one input then the other input doesn’t
show increase in synaptic strength
▪ Synapse specificity
o If you block NMDA channels, which are required for LTP, you see initial increase in
synaptic strengths caused by diff mechanism: post-tetanic potentiation (not going to be
discussed in this class)
• NMDAR is an associative molecule
o Model of post-synaptic spine in rodent neuron
o 2 different litigated ion channels for glutamate
▪ Glutamate is being released by pre-synaptic cell (not shown here)
o When you release glutamate you get current going through AMPARs
▪ Property of AMPAR: when they bind glutamate they open, let sodium into cell,
potassium out, most current driven by sodium coming in and they depolarize
• EPSP response carried by AMPARs
▪ NMDAR are blocked at rest, they have magnesium ion sitting in the receptor and
it doesn’t allow ions to pass through even though it binds glutamate
• If you depolarize neuron by enough input, high freq firing of pre synaptic
cells, it pops magnesium ion out of channel
• Now NMDAR will also carry current, but only the ones where glutamate
is there (ligand-gated ion channel)
• You need both depolarization and glutamate, the pairing of these two
things makes NMDAR associative molecule
• NMDAR permeable to calcium, it flows in and activates a bunch of
processes
o Q: so glutamate only binds to the AMPAR?
▪ It binds to both
▪ After depolarization, magnesium ion is gone and now glutamate will cause
current to flow through both
o Q: so NMDAR needs both glutamate and depolarization?
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Initial mechanisms for ltp and ltf show some differences at one point, but now words have been used for any broad long-term change in neurons: ltf in aplysia. Increase in synaptic strengths which is maintained: called long-term potentiation, esp. when maintained for a period of time. If you only give high frequency stimulation to just one input then the other input doesn"t show increase in synaptic strength: synapse specificity. Nmda current, there"s no increase in nmda current under ltp in most circumstances, you only see one in ampa current. Initial mechanism that doesn"t require protein synthesis and gene expression: making a tag or an independent form of short-term memory. Ltp: e-ltp doesn"t require proteins synthesis, l-ltp lasts longer, protein synthesis inhibitor after l-ltp it gets blocked very early afterwards, earlier than e-ltp is dependent on protein synthesis. If they don"t remember maze they don"t show that preference: a way of testing animal"s spatial memory.
