Lecture 9 BIPN148 Wi11
Transcript of Lecture 9 BIPN148 Wi11
-
8/3/2019 Lecture 9 BIPN148 Wi11
1/21
Lecture 9
Memory circuitry: The amygdala and fear
conditioning; memory allocation
-
8/3/2019 Lecture 9 BIPN148 Wi11
2/21
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.
-
8/3/2019 Lecture 9 BIPN148 Wi11
3/21
Fear conditioning is an implicit memory and can become
recallable with medial temporal lobe involvement
-
8/3/2019 Lecture 9 BIPN148 Wi11
4/21
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
-
8/3/2019 Lecture 9 BIPN148 Wi11
5/21
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
-
8/3/2019 Lecture 9 BIPN148 Wi11
6/21
In the mammalian brain there is a distinct ensemble of
neurons that code for a particular memory.How can the ensemble be identified?
-
8/3/2019 Lecture 9 BIPN148 Wi11
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
-
8/3/2019 Lecture 9 BIPN148 Wi11
8/21
Guzowski, J. F. et al. J. Neurosci. 2001;21:5089-5098
Figure 3.
-
8/3/2019 Lecture 9 BIPN148 Wi11
9/21
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.
-
8/3/2019 Lecture 9 BIPN148 Wi11
10/21
Arc mRNA is transported to dendrites and translated indentritic spines
Arc is transported todendrites and can betargeted to stimulatedsynaptic areas
Bramham et al., 2010
-
8/3/2019 Lecture 9 BIPN148 Wi11
11/21
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
-
8/3/2019 Lecture 9 BIPN148 Wi11
12/21
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
-
8/3/2019 Lecture 9 BIPN148 Wi11
13/21
Published by AAAS
L. G. Reijmers et al., Science 317, 1230 -1233 (2007)
Fig. 2. (A) A protocol was designed to detect repeated activation of neurons during learning andretrieval of conditioned fear
-
8/3/2019 Lecture 9 BIPN148 Wi11
14/21
Published by AAAS
L. G. Reijmers et al., Science 317, 1230 -1233 (2007)
Fig. 3. Reactivated neurons in the BLA during fear conditioning provide a stable neural correlate ofassociative memory
LAC ZIF
-
8/3/2019 Lecture 9 BIPN148 Wi11
15/21
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
-
8/3/2019 Lecture 9 BIPN148 Wi11
16/21
Published by AAAS
J.-H. Han et al., Science 316, 457 -460 (2007)
Fig. 2. Neurons with increased CREB function are more likely than their neighbors to be recruited to thefear memory trace
-
8/3/2019 Lecture 9 BIPN148 Wi11
17/21
Reijmers and Mayford, 2009; Frontiers in Molecular Neuroscience 2,1-8
-
8/3/2019 Lecture 9 BIPN148 Wi11
18/21
Published by AAAS
J.-H. Han et al., Science 323, 1492 -1496 (2009)
Fig. 2. Neurons overexpressing CREB preferentially activated by fear memory testing
-
8/3/2019 Lecture 9 BIPN148 Wi11
19/21
Published by AAAS
J.-H. Han et al., Science 323, 1492 -1496 (2009)
Fig. 3. Overexpressing CREB in LA neurons enhances memory induced by weak training; subsequentablation of these neurons reverses this enhancement
-
8/3/2019 Lecture 9 BIPN148 Wi11
20/21
Fear conditioning
-
8/3/2019 Lecture 9 BIPN148 Wi11
21/21
Fear conditioning