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31 Cards in this Set
- Front
- Back
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define explicit vs implicit vs declarative vs procedural memory |
explicit= conscious, intentional recollection of experiences or info implicit= previous experience alter future behaviour without conscious awareness of what was learned declarative = memories that can be consciously recalled and state in words like facts and knowledge --> this info that makes cog maps, model based thinking, introspection and insight procedural memory= memory for the performance of particular types of action - accomplished with reinforcement learning and DA signalling |
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which type of memories does the hippocampus deal with?
no hippocampus =
info comes into hippocmapus through the ______ which projects to ___ --> _____ and _______ |
EPISODIC (episodes of life, collection of past personal experience that can be explicitly stated) and SEMANTIC (common knowledge, facts, ideas and concepts like names of colours, sounds of letters, capitals of countries etc)
dont learn explicit memories
dentate gyrus --> CA3 --> CA2 and CA1 |
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what is map making? |
its used to target neurons that are spread out, you can guess where the animal is in the environment by recording as it walks around and get consistent firing in certain parts of the room
- when an animal is in a room, the group of hippocampal neurons when they are firing is specific to a certain context (room specific) |
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how can we use optogenetics to activate/inhibit specific memory engrams (aka at specific brief periods of time)?
what does the gene transcription factor tTA do?
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when putting rhodospin in active neurons for only a specific time window you need an EXTERNAL TRIGGER
it promotes gene expression by binding to the tTA-dependent gene promoter TRE |
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what is the TET-OFF system?
how does the TET-OFF cFOS-ChR2 system work? |
- doxycycline and tetracycline bind to tTA transcription factor and block it from pomading gene transcription
= where cFOS is normally expressed, the transcription factor tTA will also be expressed(no deoxycycline= tTA drives ChR2 expression) - give mice doxycycline daily so when dox is removed, active cells will express ChR2 --> the ChR2 that was made when the mouse was OFF DOX will last a few weeks before its degraded |
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is it possible to get ChR2 expressed in context specific hippocmapal neurons?
if animals received foot shocks in that room, will they be afraid whenever those neurons are stimulated? |
YES; with c-FOS --> tTA transgenic mice that had viral delivery of TRE-->ChR2 DNA into the dentate gyrus of the hippocampus - cFOS promoter drives ChR2 expression BUT ONLY IN ABSENCE OF DOXYCCYLINE
- when the DOX was removed for a day and the mice were put in a novel room and repeatedly shocked, later on the mice would freeze and exhibit fear anytime light was delivered to the dentate gyrus aka PHOTOSTIMULATON can induce fear over next few weeks |
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what 2 things did the green fluorescence label?
describe the basic experiment with DOX and foot shocks |
1. GFP expression under control of c-FOS; trhis GFP expression was limited to the nuclei of neurons that were active in the hours before death 2. regula GFP is attached to the ChR2; this can be seen filling specific cells in the dentate gyrus and the expression is obvious in the dendrites and axons of these neurons
1. on DOX= no rhdoopsin, it blocks transcription factor 2; take animal off DOX to drive ChR2 3. expose it to a novel room; fear conditioning |
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explain the experiment with optogenetic stimulation of specific memory engrams (3)
what happens? |
*** virus put in TRE promoter so the trasngenic animal with cFOS drives TTA 1. Context A/Habituation: expose them to a room photo stimulate nothing, and explore context A 2. Context B/FC- take animals off DOX put them in a room and shock them repeatedly (now express ChR2) 3. Context A/ Test: test context A after 5 days
if you put them in context A nothing happens but if you stimulate the neurons that were active in the shock room, they will freeze |
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is it possible to alter the behavioural consequence of activating specific hippocampal neurons? |
YES - mice were kept on DOX their whole life except for one day where they visited a novel room; stimulation of the neurons that were labeled during that off-DOX room visit dint produce any obvious change in behaviour
BUT
if the mice had foot shocks in a different novel room while their neutral-room labeled neurons were being photostimualted, the mice would express fear anytime they returned to that original room (the room where those neurons were labeled)
** you are activating the neurons from the neutral room (A) while you are getting foot shocks in room B so when you go back to room A they show a lot of fear (they were never shocked in room A but stimulated th neurones associated) |
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doxycycline blocks________ |
the transformation of transcription factor tTA -----> tTA dependent promoter (TRE) |
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explain the experiment where they added valence to hippocampal room representation |
1. mice kept on DOX except for a day which they visited a novel room 2. later they got foot shocks in a completely different novel room while the neutral room labeled neurons were stimulaed 3. mice expressed fear when they return to that original room (the room where neurons were labeled) |
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how are memory engrams labeled according to valence?
which 2 areas of the brain express chr2? |
once they take the animals off DOX either: 1. fear condition where mice receiving foot shocks in novel environment
2. reward condition where they are put in a novel environment with a female mouse they'd never seen before
= basolateral amygdala or the dentate gyrus
** DAPI marks cells (its an mCherry protein attached to ChR2) |
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how did they do optogenetic place avoidance? (3)
what is the difference score
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** called optogenetic place avoidance 1. baseline: the side of the chamber where mice spend more time during the 1st 3 mins is designated the preferred side 2. light is delivered into th enamels brain when he voluntarily is in that side of the chamber during mins 3-6 and 9-12 3. 2 days after baseline test (on DOX), they are put in a new room, taken off DOX and shocked; the neurons active here will then express chr2 = time spent in preferred side during photostimualtion periods MINUS time spent in preferred side during first 3 min baseline period
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what were the results from the optogenetic place avoidance experiment
what were the results from optogenetic place preference? |
mice in the experimental group (virus and foot shock) avoid areas of the chamber that trigger photo stimulating - this stimulation was targeted to basolateral amygdlaa neurons that were labeled on day 3, when animal got shocked
** hippcmapus and amygdala have same effect
= same results, putting them in a cage with a female mouse, regardless if stimulating the hippocmpaus or amygdala, they preferred that side of the chamber |
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explain the experiment for investigating whether the valence of photo simulated effect by changed (fear to reward)
what were the results? |
1. off dox, label neurons active during foot shocks 2. day 5: demonstrate that mice actively avoid was that trigger the activation of the labeled neurons 3. day 7: reactivate labeled neurons while mice are in a rewarding situation (female mice in cage) 4. day 9: see if mice now prefer to be in areas that trigger the activation of labeled neurons
results - DG neuro= was aversive on day 5 but was pleasurable by day 9 - BLA neuron aversive on day 5 but was less aversive on day 9 - conclusion is that the valence associated with specific ensembles of DG neurons can rewire but the valence associated with specific ensembles of BLA neurons cannot |
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what were the results when they transitioned neurons from reward to fear? |
DG neuron becomes less pleasurable but the BLA neuron stimulation stays pleasurable
the valence associated with specific ensembles of DG neurons can rewire but the valence associated with specific ensembles of BLA neurons cannot |
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how do mice act on day 7 when they are receiving photo stimulation of a positively valences ensemble of neurons and being foot shocked at the same time? |
photo stimulation of neurons that evoke pos associations in mice while also getting foot shocks REDUCES FREEZING BEHAVIOUR
** control animals spend 70% of the time frozen
aka the fear memory was less pronounced |
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are the projections form DG neurons actually rewiring ? |
when a labeled ensemble of DG hippocampal neurons are photostimualted they express cFOS and other neurons throughout the brain express it in response ex. the basolateral amygdala |
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in areas downstream of the hippocampus (aka amygdala), do the same or different neutrons show cFOS expression in response to DG neuron stimulations that are associated with pos vs neg emotions?
how was this tested |
1. label hippocampus and amygdala neurons that are active during foot shocks (cFOS promoter --> mCherry chr2) ---> 2. either: induce hippocampal rewiring by photo stimulating the neurons when the animal is in a pos-valenced sitch ORRR dont induce: either with no pos-valenced sitch or with no photostimulaiton ---> 3. stimulate the labeled hippocmapal neurons to see fi they activate the same or different amygdala neurons that were actie during foot shocks on day 1 |
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are the amygdala neurons that were activated by the day 5 DG neuron photo stimulation the same ones that were labeled there on day 1?
explain the procedure (3) |
1. label neurons in the DG and BLA in the same mice on day 1 (off-DOX day) during either fear or reward conditoning 2. photo stimulate the labeled neuronal ensemble in the DG on day 3 while mice are experiencing a situation of opposite valence 3. on day 5, photo stimulate the labeled neuronal ensemble in the DG to induce cFOS expression in the DG throughout the brain
results - only 20% of BLA cells activated on day 1 were also activated on day 5 when the DG neurons were photo stimulated
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explain how the valence associated with a hippocampal memory engram is bidirectionally reversible? what about the amygdala? |
when amygdala neurons are active during a foot shocker then later give them a bad experience --> its likely to activate those same neurons from the foot shock - in the hippo camps you can get them to rewire by giving them a different experience - a lot of emotional responses like fear, happiness, pleasure seems to be determined by emotions hardwired in the amygdala but the hippocmapus DOESNT - you can cause emotions by activating the amygdala and you can change this activation through experience
** when the associated valence changes, different collections of downstream neurons (in the amygdala) are activated in response to activation of the hippocampal engram
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3 types of hippocampal cells
in different environments _____ and _____ slightly remap |
1. place cells= fires anytime the animal is in a certain spot (position); they are randomly determined upon the first entrance into a novel room 2.border cells= neuron always fires when the animal is close to a wall; they retain their property from room to room 3. grid cells= fires in a periodic pattern; provide an outline of the room - if you take a mouse to a different room the size of the grid spot and difference bw the hot spots are constant (are stable features of the specific cell);
place and grid |
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explain grid cells and the combinatorial power they have
what can cause grid cells to remap? (3) |
- they are arranged as semi-independent modules which provides combinatorial power which allows of new spaces to be mapped without interfering with the memories of well established spaces
location of landmarks, time of day, motivational state
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what is hypothesized that happens when navigating a new environment ? |
an animals sense of direction initially depends on path integration - after exploring the space, animals develop a cognitive map of the area - the info you get during path integration promotes map formations and map based navigation |
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how does map formation relate to explicit memory formation? explain the 2 step process |
just like map formation, for semantic memory formation, as people go about their day, events are recorded as episodes (self referenced memories) then over time, the semantic info is extracted from the episodic memories aka first just episodic --> over time it accumulate facts and details and the map ends up not corresponding to specific things in your life |
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how can we record the activity of hundreds of hippocampal place cells over weeks? |
using a 3rd gen. GcAMP calcium based fluorescence which only produces detectable fluorescence if 3 action potentials occur in rapid succession - this type of fluorescence is slow to decay |
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what happened when the author removed the water reward and recorded the neural activity as mice ran back and forth on the 84cm track
most detectable cells had activity in ______ |
each mouse had bw 500-1000 neurons with detectable activity each day; 30% of the total detectable population showed activity on any given day
only 1 or 2 of the 10 recording sessions, 30% of the detectable population showed up each day
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how did the authors classify the cells as place cells
most place cells are _____ specific |
knowing the neural activity can allow you to predict the animals location better than chance - so, 20-30% of the detectable cells could be labeled as place cells in any given recording session (an even split between ones that were selective to the west or east direction)
direction |
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how did the percent overlap in detectable neurons across days |
if a cell had detectable activity in one session, the odds that it did so in subsequent sessions declined slightly with time (60% --> 40%) |
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what is the bayesian decoding of place cell activity
what happens 30 days later |
- recording place cells for 6 mins with mouse running back and forth then ask the computer fi ti can guess where the mouse is based on neural activity alone - 30 days later, with only 15% overlap in place cells from training session, the computer can still predict the location of the mouse |
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spatial info is preserved in ______% overlap bw coding ensembles from any 2 days
each episode in a familiar arena has a unique signature via?
how can coding turnover aid episodic memory? |
15-25%
75-85% of cells that dont overlap in coding ensembles from any 2 sessions
by creating distinct traces for events occurring in the same environment but at different times |
