Deciphering learning and memory mechanism

15, May. 2009 Inaugural Symposium

Memory and Cognition

Cognition “The psychological result of perception and learning and reasoning”“Mental functions such as the ability to think, reason, and remember”

G

BCS

Graham& Kei

Eating seafood with Min

Fado

Cues

Ret

riev

al

Reconsolidation

Incoming information

Sensoryorgans Attended to

Short-termstorage Consolidation

Long-termstorage

Rehearsed

Multistage memory model(Modified from Bower, 1967)

Outside world

Our Main Questions

2) How is memory reorganized during reconsolidation process ?

1) What molecular mechanism underlies memory consolidation process ?

3) How can we erase our bad memory?

ReconsolidationReconsolidation

ConsolidationConsolidation

ExtinctionExtinctionExtinction

Model Organisms

Aplysia Mouse1) Largest neurons in the animal kingdom

2) Simple nervous system: 20,000 neurons

3) In vitro synapse culture

1) Transgenic animals

2) Various forms of associative memory

Consolidation

Short-termmemory

Long-termmemoryConsolidationConsolidation

- Transcription & translation-independent- Modification of existing moleculesSTM

- Transcription & translation-dependent - Structural changes : synaptic growthLTM

Consolidation of LTF in Aplysia

• Transcription factors involved in consolidation • 5-HT receptor

(Lee et al., M

ol B

rain, 2

008)

Reconsolidation

Consolidated state

Labile state

?Proteinsynthesis

Reactivated memory becomes labile and modifiable, and has to undergo some new process of stabilization depending on de novo protein synthesis. ( Misanin et al, 1968; Nader et al., 2000; Dudai, 2004 )

Protein degradation

MEMORY

Protein degradation and resynthesis in the synapse induced by memory retrieval

Kaang, B.K.Kaang, B.K.

Collingridge, G.L.Collingridge, G.L.

Zhuo, M.Zhuo, M.

Lee, I.Lee, I. Kim, S.J.Kim, S.J.

Cho, K.Cho, K.

“Silencing” or “TB” project

T.V.P Bliss & Lømo (1973) J. Physiol.

Synaptic plasticity is both necessary and sufficient for the information storage in the brain.

Hypothesis of TB project

• Testing the hypothesis

1) Memory is formed through strengthening a unique set of synaptic connection.

2) One neuron might attend to several memory circuits. If specific synapses are inactivated, specific memory would be impaired.

Event AEvent A

Event BEvent B

Synaptic specificity

Thanks to:Lab members Deok-Jin JangHyoung KimSue-Hyun LeeChi-Hoon Lee Jae-Ick KimHyoung-Gon KoHye-Ryeon LeeHeejung JunJun-Hyeok ChoiNam-Kyung YuSun-Lim ChoiNuribalhae LeeJung-Eun KimChuljung KwakSuwon ParkYeon-Su Chae