Lecture 9 BIPN148 Wi11

8/3/2019 Lecture 9 BIPN148 Wi11

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Lecture 9

Memory circuitry: The amygdala and fear

conditioning; memory allocation


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Recommended reading

1: Reijmers LG, Perkins BL, Matsuo N, MayfordM. Localization of a stable neural correlate ofassociative memory. Science. 2007 Aug31;317(5842):1230-3.

2: Guzowski JF, Setlow B, Wagner EK, McGaughJL. Experience-dependent gene expression in therat hippocampus after spatial learning: acomparison of the immediate-early genes Arc, c-fos, and zif268. J Neurosci. 2001 Jul15;21(14):5089-98.

3: Han JH, Kushner SA, Yiu AP, Cole CJ, Matynia A,Brown RA, Neve RL, GuzowskiJF, Silva AJ, JosselynSA. Neuronal competition and selection duringmemory formation. Science. 2007 Apr20;316(5823):457-60.

4: Han JH, Kushner SA, Yiu AP, Hsiang HL, Buch T,Waisman A, Bontempi B, Neve RL, Frankland PW,

Josselyn SA. Selective erasure of a fear memory.Science. 2009 Mar 13;323(5920):1492-6.


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Fear conditioning is an implicit memory and can become

recallable with medial temporal lobe involvement


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TRAINING

CONTEXTUAL TEST CUED TEST

Animal is placed in novel context

Hears a toneReceives foot shock

Animal is returned to same context

Test for freezing behavior

Animal is placed in modified context

Hears a toneTest for freezing behavior

Implicit Memory: Fear Conditioning


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Figure 8: Auditory fear conditioning pathways. The auditory conditioned stimulus (CS) and somatosensory (pain) unconditioned

stimulus (US) converge in the lateral amygdala (LA). The LA receives inputs from each system via both thalamic and cortical inputs. CS-

US convergence induces synaptic plasticity in LA such that after conditioning the CS flows through the LA to activate the central

amygdala (CE) via intraamygdala connections. CE in turn controls the expression of behavioral (freezing), autonomic and endocrine

responses that are components of the fear reaction. Other abbreviations: B, basal amygdala; CG, central gray; LH, lateralhypothalamus; ITC, intercalated cells of the amygdala; PVN, paraventricular nucleus of the hypothalamus


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In the mammalian brain there is a distinct ensemble of

neurons that code for a particular memory.How can the ensemble be identified?


7/21Copyright 2001 Society for Neuroscience

Guzowski, J. F. et al. J. Neurosci. 2001;21:5089-5098

Immediate early genes as markers of neuronal activity


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Guzowski, J. F. et al. J. Neurosci. 2001;21:5089-5098

Figure 3.


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Immediate early genes and synaptic plasticity

The zif-268 (egf-1) gene andfos gene encode transcription factors with bindingsites on the promoters of hundreds of different genes

IEGs are induced by high-frequency stimulation that triggers hippocampal long-term potentiation (LTP), a leading model of synaptic plasticity thought to underliememory formation (Bliss and Lmo 1973; Bliss and Collingridge 1993).

Most importantly, their expression is actually required for the long-term

maintenance of hippocampal LTP, as well as spatial and nonspatial long-termmemories.


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Arc mRNA is transported to dendrites and translated indentritic spines

Arc is transported todendrites and can betargeted to stimulatedsynaptic areas

Bramham et al., 2010


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The transport of arc mRNA allows for measurements ofneuronal activation at two time points

arc red

zif - green

A/B delay:5 min exposure to environment A

20 min delay

5 min exposure to B

25 min delay


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Published by AAAS

L. G. Reijmers et al., Science 317, 1230 -1233 (2007)

Fig. 1. (A) Tagging of activated neurons is achieved by two transgenes present in the TetTag mouse

tTA tetracycline transactivator

tTA* - Dox-insensitive tTA

Fos-prom Fos


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Published by AAAS


Fig. 2. (A) A protocol was designed to detect repeated activation of neurons during learning andretrieval of conditioned fear


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Published by AAAS


Fig. 3. Reactivated neurons in the BLA during fear conditioning provide a stable neural correlate ofassociative memory

LAC ZIF


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Published by AAAS

J.-H. Han et al., Science 316, 457 -460 (2007)

Fig. 1. Auditory fear conditioning activates CREB in ~20% of LA cells in wild-type (WT) mice; increasingCREB function in a similar portion of LA neurons rescues the fear memory deficit in CREB-deficient

mice


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Published by AAAS


Fig. 2. Neurons with increased CREB function are more likely than their neighbors to be recruited to thefear memory trace


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Reijmers and Mayford, 2009; Frontiers in Molecular Neuroscience 2,1-8


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Published by AAAS


Fig. 2. Neurons overexpressing CREB preferentially activated by fear memory testing


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Published by AAAS


Fig. 3. Overexpressing CREB in LA neurons enhances memory induced by weak training; subsequentablation of these neurons reverses this enhancement


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Fear conditioning


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Fear conditioning

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Lecture 9 BIPN148 Wi11