PSYC 310 Lecture Notes - Lecture 14: Non-Rapid Eye Movement Sleep, Episodic Memory, Memantine
7 May 2018
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Hippocampus and place cells
• Inside HC there are certain cells place cells whose activity correlates with specific
locations
• Activity at certain points can be used to make a heat map: specific cell shows red center
that dissipated as it went off the sides
o Activity concentrated to given spot in space
• Hippocampus cell types
o There are many different cell types
o CA3 & CA1 : place cells and time cells
▪ Time cells: fire for a certain duration of time (keep track for specific
durations of time)
o Entorhinal cortex
▪ Border cells on edges of room
▪ Head cells: direction of head
▪ Grid cells: make regular patterns of activity that make grid over space
you’re in
• Paper: long-term dynamics of CA1 HC place codes
o What place cells are recruited, how does this change over time, and is it different
or the same populations?
o A way to individually visualize these cells: micro-endoscopy
▪ G-CaMP but instead of global fluorescence you get fluorescence of
individual cells
▪ Microscope attached to head
▪ Record through microscope the individual fluorescence of individual
neurons
▪ Computer manually detects how much fluorescence is in each circled area
o A task to assess place cell recruitment
▪ Initially have mouse on linear track where he walks back and forth
• Motivate him to go along the track
▪ Get him to be deprived off water, really thirsty, and have water on either
end
• He goes to each end and drinks water back and forth
▪ 10 days when they record cells: omit water, just want to see as animal is
moving along that track what do the cells do?
o When they look under microscope they see that they can get around 500-1000
different neurons active at some point along 10 days of recording
▪ How many of these cells were only active on 1 day? On 2 days?
▪ On this given day: how many total cells were active? 30%
▪ 60% activity on only 1-2 days: very little cells had activity consistently
throughout 3 days or more
▪ Place cells: a certain portion of these measured cells might not even be
place cells. So just get the place cells and count those
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• On a given day I can label about 20-30% of total cells as being
place cells
▪ Do place cells collectively represent the entire track?
• Each row represents single neurons activity along track
•
• Representation width is 20-30cm, pretty consistent day to day
▪ Reoccurrence and decoding
• There’s 50% overlap each day
• Probability that if you have a neuron active on day 1, probability of
seeing it on another day X is 50%
o Specifically, about place cells: 15-25% (~20%)
o You have 20% overlap of which neurons get classified as
place cells from day to day
o If I use the same neurons I saw on day 1 and go through
each other recording session do I still see generally the
same representation of the track?
o There is still a consistent representation of the whole track:
even though the neurons are slightly different
o Aka, 20% overlap is sufficient to predict location of
animal on a later day
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o
• Memory Engrams in the HC (next paper)
o You have an animal in certain context: inside that context a certain group of
neurons in HC will collectively, uniquely represent this context specifically
▪ An engram
o Can we isolate specifically the engram representing any context?
o Using tet-off system
▪ You have this system where you have a gene and a promotor TRE which
requires transcription factor called TTA
▪ tta goes to this region and allows for transcription
▪ If you add DOX it binds to tta and makes it not possible to attach to Tre
▪ There’s no tta attached to tre no more transcription, no expression of
anything
▪ If you remove DOX you re-allow tta to go and bind to Tre
▪ When tta is bound to tre you can have transcription
o Isolating ChR2 to a memory engram
▪ If you want to isolate ChR2 specifically to that memory engram:
• C-fos tta transgenic mouse
o Neurons that are recently active making c-fos will express
Tta
• Inject virus inside dentate gyrus: Tre-ChR2
• Cells that are recently active will be making tta
• Those cells will be making tta and that will bind to Tre of the
construct on middle left (in circuit loop diagram) that allows for
transcription of channelrhodopsin
• Add DOX to stop any transcription from happening
• Mouse put on DOX for whole life until moment when you want
transcription of specific protein to happen
o Reactivating the engram
▪ On DOX: habituating to context
▪ Have specific point where you bring to context B and take them off dox
and foot shock them
▪ At that point, any cell recently active is going to be expressing ChR2
▪ Then put them back on Dox
▪ Go in and shine light into DG
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Document Summary
30: 60% activity on only 1-2 days: very little cells had activity consistently throughout 3 days or more, place cells: a certain portion of these measured cells might not even be place cells. If you add dox it binds to tta and makes it not possible to attach to tre: there"s no tta attached to tre no more transcription, no expression of anything. If you remove dox you re-allow tta to go and bind to tre: when tta is bound to tre you can have transcription, isolating chr2 to a memory engram. If you want to isolate chr2 specifically to that memory engram: c-fos tta transgenic mouse, neurons that are recently active making c-fos will express. Reshine to remind animal of positive engram: did we revert depression symptoms, two groups with effects: 5 days of stimulation and also no stress group, cause no sig difference between no depression to start with and the.
