Neural basis of Memory consolidation and storage

1. Neural Basis of
Memory Consolidation and Storage

2. Overview
Introduction
Implicit memory
– Habituation and dishabituation
– Sensitization
– Associative learning
– Implicit memory in mammalian brain
Explicit memory
– Episodic memory
– Semantic memory
– Place cells, grid cells & memory
– Contextual fear memory Engrams
– Systems consolidation

3. Introduction
• Learning is the process by which we acquire
knowledge about the world
• Memory is the process by which that knowledge
of the world is encoded, stored and
later retrieved
Kandel et al.,Principles of Neural Science, 5th ed,2013

4. Patient H.M : William Scoville & Brenda Milner
Henry Molaison, aged 60: Copyright J, Ogden, "Trouble In Mind" 2012

5. Patient H.M : MRI image
Corkin et al., J Neurosci. 1997

6. Findings in patient H.M
• Intact intellectual & perceptual functions
• Sustained attention
• Failure to convert transient, immediate
memory into stable long-term memory
• Earlier memories before surgery –normal
• Had insight about his disease

7. Inference made from study of patient H.M
• Memory is a distinct cerebral functions, separable
from perceptual & other cognitive functions
• Fundamental distinction between immediate & long-
term memory
• Identification of medial temporal lobe as crucial for
transition of short-term memory into long-term
memory
• Medial temporal lobe is not the ultimate storage for
previously acquired memories

8. Milner et al., 1962
Kandel et al.,Principles of Neural Science, 5th ed,2013
Skill-like abilities in patient H.M

9. Peter Graf and Daniel L. Schacter, Journal of Experimental Psychology. 1985
Priming in amnesia patients
BLA _ _ _ _COVERING

10. Long term memory
Explicit
(Declarative)
Implicit
(Non-declarative)
Semantic
(Facts)
Episodic
(Events)
Non- associative
• Habituation
•Sensitization
Associative
•Classical
•Operant conditioning
Priming Procedural
Kandel et al.,Principles of Neural Science, 5th ed,2013

11. Implicit memory

12. Habituation is the decrement of a behavioral
response that occurs when an initially novel
stimulus is repeatedly presented.
Dishabituation is the restoration of a previously
decremented response, occurs following a
change in the stimulus pattern, such as the
presentation of another, stronger stimulus.

13. Habituation and dishabituation
Pinsker et al., Science, 1970
Aplysia californica

14. Pinsker et al., Science, 1970
Habituation or fatigue

15. Kupfermann et al., Science, 1970

16. Castellucci et al., Science,1974

17. Castellucci et al., Science, 1974

18. Sensitization
Kandel et al. , Principles of Neural Science, 5th ed. 2013

19. Short term sensitization
Purves et al., Neuroscience 6th ed.2019

20. Long-Term sensitization
Purves et al., Neuroscience 6th ed.2019

21. Bailey et al., Proc. Nati. Acad. Sci. 1988
Long-term memory in Aplysia modulates the
total number of varicosities of sensory neurons

22. Bailey et al., Proc. Nati. Acad. Sci. 1988

23. Associative learning (Classical Conditioning)
Hawkins et al., Science. 1983

24. Hawkins et al., Science. 1983

25. Squire et al.,Fundamental of neuroscience,4th ed,2012

26. Long-Term Synaptic Facilitation Is Synapse Specific
Martin et al., Cell. 1997

27. Martin et al., Cell. 1997
Capture of long-term facilitationLong term facilitation

28. Casadio et al., Cell. 1999

29. Casadio et al., Cell. 1999

30. Kandel et al., Principles of Neural Science, 5th ed. 2013
Inactive (soluble) CPEB
Active (aggregate) CPEB
N-Actin
tublin
Long-term facilitation requires
local protein synthesis for maintenance

31. Striatum in habitual response memory
Packard et al., Neurobiology of Learning and Memory. 1996

32. Cerebellum-Dependent Memory
Thompson & Kim, Proceedings of the National Academy of Science USA, 1993
Eyeblink Classical
Conditioning
Auditory
nuclei
Pontine
nuclei
Cerebellar cortex
interpositus
nucleus
Red
nucleus
Cranial
motor
nuclei
Inferior
olive
Trigerminal
nucleus
Reticular
formation
All other targets of superior
cerebellar penduncle
Eyeblink
UR & CR
Mossy fibers
Climbing
fibers
Tone
CS

33. Amygdala in emotional memory

34. Squire et al.,Fundamental of neuroscience,4th ed,2012

36. Explicit memory

37. Explicit Memory Processes
process by which
new information
is attended and
linked to existing
information in
memory
neural
mechanisms and
sites by which
memory is
retained over time
process that makes
the temporarily
stored and still
labile information
more stable
process by which
stored
information
is recalled
Kandel et al.,Principles of Neural Science, 5th ed. 2013
StorageEncoding Consolidation Retrieval

38. Wagner et al. Science. 1998
Episodic memory encoding for verbal experience

39. Episodic memory encoding for visual experience
Brewer et al., Science. 1998

40. Semantic memory
Martin et al., Curr Opin Neurobiol.2001
2) medial fusiform gyrus
3) Left inferior temporal sulcus
5) left ventral premotor cortex
1) lateral fusiform gyrus
4) right superior temporal sulcus

41. Hippocampal Sub-regions

44. Reijmers et al., Molecular Neuroscience 2009

45. Long-Term Potentiation at the CA3–CA1 Synapse
Purves et al., Neuroscience 6th ed.2019

46. Purves et al., Neuroscience 6th ed.2019

47. Long-term synaptic depression
Purves et al., Neuroscience 6th ed.2019

48. Navigation and memory
Buzsaki et al., Nature Neuroscience.2015
Episodic memory Semantic memory

49. Place cells
J. O'Keefe & J. Dostrovsky, Brain Research 1971

50. J. O'Keefe and D.H. Conway. Exp. Brain Res.1978

51. J. O'Keefe and D.H. Conway. Exp. Brain Res.1978

52. Grid cells
Hafting et al., Nature. 2005

53. Solstad et al.,Hippocampus. 2006

54. Contextual Fear memory engrams
Liu et al., Nature. 2012
Fos- prom tTAFos-prom
ChR2-EYFP
Fos- prom tTAFos-prom
TRE ChR2-EYFPTRE
Doxycycline
Dentate gyrus

55. Dox on : Context A - 5 days of test session
Liu et al., Nature. 2012
Dox On : Context A - 5 days of habituation
12min/day : 3min - 3min - 3min - 3min
off on off on
Dox Off : for two days
Next day - Context B : 1 day training
500s 500s 500s
3 h 3 h

56. Dentate gyrus cells that express endogenous C-Fos
during training & therefore become labelled by
ChR2-EYEP, define an active neural population that
is sufficient for memory recall upon subsequent
reactivation
Liu et al., Nature. 2012

57. Dox on : Context A - 5 days of test session
Liu et al., Nature. 2012
Dox On : Context A - 5 days of habituation
12min/day : 3min - 3min - 3min - 3min
off on off on
Dox Off : for two days
Dox On - Context B : 1 day training
500s 500s 500s
3 h 3 h
Next day - Context C : 1 day

58. Liu et al., Nature. 2012
Light induced fear memory recall is context specific

59. Liu et al., Nature. 2012

60. Place cells vs Engram cells
Tanaka et al., Science 2018

61. Tanaka et al., Science 2018
Engram cells are place cells with lower spatial stability & accuracy, but with activity
that can reliably and quickly reflect contextual identity

62. Engrams and circuits crucial for systems
consolidation of a memory
Kitamura et al., Science 2017

63. Redondo et al., Nature.2014

65. Thank you