Interrogating the role of hippocampal sharp-wave ripples in spontaneous learning

Shay(ok) Dutta

June 14, 2023

Acknowledgements

Monies!

NSF CAREER (CBET-1351692), NSF BRAIN
EAGER  (IOS-1550994), NIH R01NS115233, HFSP Young Investigator’s (RGY0088)

Lab

Current: Dr. Caleb Kemere

Ziying, Sibo, Della, Kayla, Dani

Former: Drs. Josh, James, Etienne, Alex; Mentees! Amy (MD stud!), Jim (NSF GRFP!), Ariel (Carnegie Student Fellow!); MS! Jill, Eric

Others

Drs. Jacob Robinson, Rob Raphael, Jon Flynn, Joe Young, Daoyun Ji, Amanda Singer, Elysse Orchard,  MS! Kelly Kim/Campbell

💰

Interrogating the role of hippocampal sharp-wave ripples in spontaneous learning

Where to begin?

Active Behavior

Quiescence

hmm...

Where to begin?

Quiescence

hmm...

Active Behavior

What does this look like?

What does this look like?

What does this look like?

Where to begin?

Quiescence

hmm...

Active Behavior

How does the brain store this configuration of the world?

Background

Knerim et al. Philosophical Transactions of the Royal Society B: Biological Sciences 2014

Clark et al. J. Neuro 2000 showed lesioning HPC impairs novelty preference

Hippo 101

Hippo 101

Figure concept adapted from Colgin, Nat. Neuro. Reviews 2015

Hippo 101

Are SWRs related to storing the configuration of the world?

Figure concept adapted from Colgin, Nat. Neuro. Reviews 2015

SWRs & ORM

Larkin et al. Hippocampus 2014

Are SWRs related to storing the configuration of the world?

How can we test this?

Dutta et al. JNE 2018

Let's see it in action!

Are we doing it right?

Dutta et al. JNE 2018

Are we doing it right?

Dutta et al. JNE 2018

Let's check out validity!

Let's test this!

ORM No More!

Are SWRs related to storing the configuration of the world?

YES!

Hippo 101

SWR

So, why is this cool again?

  • Ripples have been causally linked to object-location memory consolidation!
  • Natural, foraging, spontaneous memory task. No reward or forced structure!
  • The disruption and chance level discrimination between objects is a result that can be achieved day-after-day

Object Recognition Memory

Object Recognition Memory

Object Recognition Memory

What is the disruption doing?

What is the disruption doing?

Is this a reasonable or fair comparison across animals?

What is the disruption doing?

Is this a reasonable or fair comparison across animals?

What is the disruption doing?

There seems to be a difference in the distributions!?

What is the disruption doing?

Trying to target long ripples

Trying to target long ripples

How can we modify this algorithm to detect longer ripples?!?!

Trying to target long ripples

In action!

Long ripple disruption!

Conclusions

Contributions (i.e., I've scienced!?)

  • Causal relationship established between hippocampus and object-location memory
  • First ripple disruption task that can be run repeatedly with chance level performance!
    • New memory formation, consolidation and place field stability questions can be asked!
  • First ripple disruption task with result with a behavioral effect that is in shown in a natural, foraging, curiosity driven behavior innate across animals!
  • Longer ripples clearly have some relationship with better memory consolidation. Perhaps they are needed for full strtength of memory?

Real Conclusion

  • September 2014: I asked Caleb what a life cycle of a PhD Student in his lab was based on his vision
  • August 2015: I asked Jacob what a life cycle of a PhD Student in his lab was based on his vision.

Questions?

What I hope to do here!

Fear, anxiety, depression, stress, etc. & therapeutic modulation?

(i.e., combining things --> actually contribute to humans!?)

Zheng & Colgin Nat. Neuro. News & Views 2017

Hippo Background

Wu et. al, Nat. Neuro. 2017

Zheng & Colgin Nat. Neuro. News & Views 2017

Proposal for Cool Things?