FRANK Loren  Hippocampus  Memory Replay Jan 30 2012

psych
episodic memory
spatial navigation;  psychiatric and neuro disease

LTP/rapid plasticity  CA1 to CA3... get  LTP with a single burst of activity
spatial specifricty
rhythymic activity

so  how does it work...
so how does it it instantiate memory

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Learning and the HC Circuit

Neocortex  slow plasticity
inputs going to neocortex  (sensory inputs)

Neocrotex  pattern gets encoded and  that is transmitted to
HC which has rapid plasticity  but then  consolidation (perhaps during sleep)
things get consolidated  into patterns in neocortex...

also important role of HC in retrieval...
lesion/ disease studies eg patient HM...  without HC  cannot retrieve...

today will frocus on retrieval...

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encoding,  retrieval, and consolidation  (literature parses it into those 3)

animal exploring its world = active exploration
place fields and theta....
animal runs thru a maze and is successively at 3 difft locations  , and then u see
firing rate in place cell 1, 2, 3 in succession...

then later  during sleep   get replay

in 80 ms  get replay of cells  1,2,3 in rapid succession:  is that memory consolidation...?

hypothesis:  HC sends out the 1,2,3  msg  over and over:
standard model...

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he shows clip of this in CA1  neurons  succesively  firing  as rat goes around circular maze...

Questions:  what patterns of neural actiivty might contribute to memory?

done by Mattias M  + Frank in Nature Neurosci....

Replay with the Environment  E1

W shaped maze...  starting from R arm and going to middle  and then
going from middle to end of R arm...

maze run takes 5 to 10 seconds...

but  it gets replayed in 200 ms...
see Foster and Wilson  2006
or Diba and Buzsaki  2007...

David Foster in Matt Wilson's lab in 2006...

sl  Decoding  Replay Activity...

identify candidate events where at least 5 cells were active...

u do get  a decoded  version of space as rat is running maze and pausing....

place cells reflect where animal actually is...
but when animal stops  and you look at E1
is this an animal  recalling where it has been???

it is there  256/580  (44%) of candidate events are signif  p<10**-10

seems that HC is actually replaying  trajectory...

how abt  awake replay of E1 in E2...

E1  is a W  E2 is an E

rest box  then runs E1  then rest box  then E1  again back to rest box  then E2 then back to rest box...

ripple events are  high freq events..
how well does activity  correspond to past experirence... answer is  abt 10 to 20%....

they work with Surya Ganguli

before sleep u see hints of the pattern before the sleep

K.Boahen Q:  do u see ripple events when animal is moving?
A  big ripples r mainly when animal is still or moving slowly .

*  experience within a day leads to robust, long-lasting replay while the animal is awake.

replay is more robust in awake than in quiescent state...etc.

Magie Carr did this work...

  Replay  is concurrent but not coherent across HC...

ripple across HC is concurrent but not coherent....

Maggie did all this...

activity in difft freq bands...

requirements for synchronization of replay

consistent across SWRs

shud have precise temporal structure  

there is a time delay since ripple detection... peaks around  100 msec later  (gamma)

the bigger the ripple, the more gamma...

Ca1 to CA3  gamma phase aligns during SWRs...

is gamma organizing activity  is it entraining spiking...
must have everybody  locked together...

you do get  incr  phase locking  at 100 msec  after the ripple...

Surya is in audience...

areas do oscillate together at the time of a ripple...

CA3 fires first and then 7 ms later  CA1 fires...

CA3  is  synched to gamma...

 gamma entrainment is predictive of replay quality...

when replay represents a known past experience, it really is correlated with gamma...
improves quality of replay...

these cells are restricted to be ones that  respond to places  says Maggie...

conclusion:  gamma power and coherence transiently incr during SWR = slow wave ripple...

CA1 and CA3  gamma phase alignment and coherence increase during SWRs.

Q   causality flow...  rhythms  are result of extracellular currents...
we think of it as part of one  mechanism...

ripple  oscil is epiphenomenal  (as a result of  neuron firing
Kwab. Boa:  is there a signif  effect of phase or amplitude of rhythm...

SWR = sharp wave ripple...

Q:  relation btwn  sleep events and awake replay events

ripples happen from 4 to 1 time per second...
 big ones perhaps  once a second, when animal is still.

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can we say something CAUSAL...

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hypothes 1)  awake replay could serve as a continuous mechanism for memory consolidation

and 2)  awake replay cud be important for memory recall for guiding ongoing behavior..

O'Neill and Csicsvari 2010  or
carr, jadhav, and frank in 2011...

Anthony W: is  new environment driving the recall of old enviro... how r they triggered?...

A  there is some biasing of retrieval  by where u are at now...

W-track...  start in the right arm and go in-bound into center 

another is  start at the left and go to the center... another inbound

inbound trials....

outbound trials  (I last did an inbound run, now i have to do an outbound).. uses working memory...

lesioned animals  can't do it...

HC is required for learning new stuff...

how do they get inbound trials wrong...
answer:  go from one outer arm to  the other outer arm.

vHC = ventral  HC commissure.. where they cross midline...

expt:  8 days of behavior:

compare  ripple  memory  to  control stim  for 100 ms  but later on, so as not to interfere with ripple
compare to ripple disruption...

ripple disruption  really is disrupting to behavior...
animal really cannot do task if ripples are disrupted...

do get clean separation btwn ripple disrupted mice; control disruption; and normal mice...

control stim does not disrupt  learning...

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conclusions

* we are able to specifically disrupt HC ripples in the awake state during behavior

ripple  disruption DOES disrupt behavior specifically...

every time u remember something u  consolidate it a bit more...

place cells are associated with the current loaction

Maggie = Margaret Carr

Q  diff btwn working memory and "reference memory"

replay = mental exploration of space  (to decide what to do next... what can u do next)
(then must integrate that with task rules)

Jay Q:  learning as opposed to performance?...

how abt transfering from  HC to  basal ganglia  once it becomes more automated...
basal ganglia wud be more classical  reward based  learning..
HC is more "thinking about it””

in genl it is the case that the more u retreve something, then more u consolidate it...

brain may not care abt  whether u retrieve it during sleep or while awake....

during sleep... free form patterns of activity...easier to explore the whole space....

they are sampling from only perhaps 80 cells out of 200,000 or so

perhaps in future use calcium imaging...

jay has simulated this...

spike plasticity  happens in 20 msec...

how do u compress  an activity that unfolds over  minutes or hours  into
a pattern  that unfolds at the time scale of LTP ...

inputs to HC are  from superficial entorrhinal
output from HC is to deep layers of entorrhinal...