A spiking neuron model of pharmacologically-biased fear ...
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freezing more less Figure 2: Simulated freezing under twelve pharmacological manipulations musc oxy 5-HT DA PAG CeM CeL tone CeL o� BLA tone BLA cage Figure 1: Fear conditioning (left) and expression (right) CeM CeL BLA pre cond. ext. post Central Medial (CeM) Central Lateral (CeL) Basolateral (BLA) o� periaqueductal gray (PAG) hippocampus cortex o x y D A 5 - H T excite inhibit learn receptor a b GABA interneuron c error signals (BLA shock - BLA tone ) + CeL shock - CeL tone BLA shock - BLA cage + (BLA shock - BLA tone ) - a b c motor thalamus spinal cord cortex Anatomically-detailed spiking neuron model of the amygdala Learning rules drive fear associations by updating synaptic weights during training Simulated the impact of pharmacology on conditioning, extinction, and expression Results consistent with behavioral and neural data Muscimol (musc): GABA A agonist that inhibits neural activity in the targeted population [ 3, 5, 7] Oxytocin (oxy): Neuropeptide implicated in fear expression. Receptors in CeL off . [4] Dopamine/Seratonin (DA/5-HT): Implicated in fear learning. Receptors in GABAergic BLA interneurons [6] Neural Engineering Framework [ 1]: methods for building biologically-plausible, functional networks using spiking neurons Perscribed Error Sensitivity [ 9] : error- and activity- dependent learning rule for updating synaptic weights Abstract Background [1] Eliasmith and Anderson. MIT press, 2003. [2] Duvarci and Pare. Neuron, 2014. [3] Muller et al. Behavioral neuroscience, 1997 [4] Viviani et al. Science, 2011 [5] Ciocchi et al. Nature, 2010 [6] Ehrlich et al. Neuron, 2009. [7] Sierra-Mercado, Padilla-Coreano, and Quirk. Neuropsychopharmacology, 2011. [8] Akirav, Raizel, and Maroun. European Journal of Neuroscience, 2006. [9] MacNeil and Eliasmith. PloS one, 2011. Results Figure 2 shows fear expression (mean PAG activity during tone, n=10 trials) for twelve simulated experiments. References Model Anatomical reconstruction of amygdala [2]; 4200 spiking neurons, 16 ensembles, 3 learned connections Inputs: tone, shock, cage Outputs: decoded spikes Conditioning: (+) error increases response of excitatory tone neurons (CeL, BLA) when tone and shock coincide Extinction: (-) error increases response of inhibitory cage neurons (BLA) when tone present without shock Expression: within CeM, tone responses from CeL and BLA compete with cage response from BLA Pharmacology: (+/-) current applied to neurons Control experiments confirm model's fear learning no freezing without conditioning (cond.) more freezing after cond. less freezing after extinction (ext.) Muscimol's observed e�ects are captured by the model musc to CeL causes unconditioned freezing musc to CeL @ cond. impairs learning musc to BLA @ cond. impairs learning musc to BLA @ ext. impairs learning musc to BLA @ test impairs expression Modulator's e�ects are also recreated by the model oxy to CeL @ cond. preserves learning oxy to CeL @ test impairs expression DA to BLA @ cond. facilitates learning 5-HT to BLA @ cond. impairs learning vs vs vs vs vs vs vs vs vs vs vs [5] [5] [3] [7,8] [3] [4] [4] [6] [6] A B C D E F G H I J K L github.com/psipeter/anatomical_amygdala Society for Neuroscience 2019 computational neuroscience research group compneuro.uwaterloo.ca A spiking neuron model of pharmacologically-biased fear conditioning in the amygdala Centre for Theoretical Neuroscience, University of Waterloo | http://ctn.uwaterloo.ca/ Peter Duggins [email protected] Chris Eliasmith [email protected]
Transcript of A spiking neuron model of pharmacologically-biased fear ...
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Figure 2: Simulated freezing under twelve pharmacological manipulations
musc oxy 5-HTDA
PAG CeM CeLtone CeLo� BLAtone BLAcage
Figure 1: Fear conditioning (left) and expression (right) CeMCeLBLA pre cond. ext. post
Central Medial(CeM)
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Anatomically-detailed spiking neuron model of the amygdala
Learning rules drive fear associations by updating synaptic weights during training
Simulated the impact of pharmacology on conditioning, extinction, and expression
Results consistent with behavioral and neural data
Muscimol (musc): GABAA agonist that inhibits neural activity in the targeted population [3, 5, 7]Oxytocin (oxy): Neuropeptide implicated in fear expression. Receptors in CeLoff. [4]Dopamine/Seratonin (DA/5-HT): Implicated in fear learning. Receptors in GABAergic BLA interneurons [6]
Neural Engineering Framework [1]: methods for building biologically-plausible, functional networks using spiking neuronsPerscribed Error Sensitivity [9] : error- and activity-dependent learning rule for updating synaptic weights
Abstract
Background
[1] Eliasmith and Anderson. MIT press, 2003.[2] Duvarci and Pare. Neuron, 2014. [3] Muller et al. Behavioral neuroscience, 1997[4] Viviani et al. Science, 2011[5] Ciocchi et al. Nature, 2010[6] Ehrlich et al. Neuron, 2009.[7] Sierra-Mercado, Padilla-Coreano, and Quirk. Neuropsychopharmacology, 2011.[8] Akirav, Raizel, and Maroun. European Journal of Neuroscience, 2006.[9] MacNeil and Eliasmith. PloS one, 2011.
Results
Figure 2 shows fear expression (mean PAG activity during tone, n=10 trials) for twelve simulated experiments.
References
Model
Anatomical reconstruction of amygdala [2]; 4200 spiking neurons, 16 ensembles, 3 learned connections
Inputs: tone, shock, cage Outputs: decoded spikes
Conditioning: (+) error increases response of excitatory tone neurons (CeL, BLA) when tone and shock coincide
Extinction: (-) error increases response of inhibitory cage neurons (BLA) when tone present without shock
Expression: within CeM, tone responses from CeL and BLA compete with cage response from BLA
Pharmacology: (+/-) current applied to neurons
Control experiments confirm model's fear learning
no freezing without conditioning (cond.)
more freezing after cond.
less freezing after extinction (ext.)
Muscimol's observed e�ects are captured by the model
musc to CeL causes unconditioned freezing
musc to CeL @ cond. impairs learning
musc to BLA @ cond. impairs learning
musc to BLA @ ext. impairs learning
musc to BLA @ test impairs expression
Modulator's e�ects are also recreated by the model
oxy to CeL @ cond. preserves learning
oxy to CeL @ test impairs expression
DA to BLA @ cond. facilitates learning
5-HT to BLA @ cond. impairs learning
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github.com/psipeter/anatomical_amygdalaSociety for Neuroscience 2019
computational neuroscienceresearch groupcompneuro.uwaterloo.ca
A spiking neuron model of pharmacologically-biasedfear conditioning in the amygdala
Centre for Theoretical Neuroscience, University of Waterloo | http://ctn.uwaterloo.ca/
Peter [email protected]
Chris [email protected]
