Behavioral Neuroscience: Fear thou not. Rony Paz
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1 Behavioral Neuroscience: Fear thou not Rony Paz
2 Thoughts What is a reward? Learning is best motivated by threats to survival? Threats are much better reinforcers? Fear is a prime motivator Decreases behavior Increases behavior Presented Positive punishment Positive reinforcer Taken away Negative punishment Negative reinforcer Taking drugs? More fun, less withdrawal
3 Percent Freezing Classical fear conditioning Habit. Cond. Extinction Next Day Trials Sham CS-US pairing Tone = conditioned stimulus (CS) Foot-shock = unconditioned stimulus (US) Freezing = conditioned response (CR-UR)
4 Contingency: co-occurence Schedules of reinforcement: Variable/fixed interval/ratio
5 More than contingency: Surprise / added information Aversive conditioning Blocking
6 Rules of thumb for conditioning strength Backward < simultaneous < trace < delay In trace: short interval > long interval In delay: short CS > long CS Salience of the CS Strength of the US Spaced trials is better than massed trials (the ratio between inter-trial-interval and the CS) But notice it is hard to estimate backwards learning
7 Trans-reinforcer blocking Conditioned inhibition Suggests common brain mechanisms
8 Amygdala
9 Amygdala and its basolateral complex (BLA) BLA evolution parallels that of the prefrontal cortex BLA cell types reminiscent of cortex Cortical projections are much more extensive in primates Most cortical projections of the amygdala originate from BLA (none from CEA)
10 Fear circuit Periaqueductal lateral Paraventricular Gray hypothalamus nucleus (midbrain) (hypothalamus) Ledoux, Mcgaugh, Davis
11 Neurons acquire tone responses after conditioning
12 LTP in the LA is required NMDA (N-methyl-D-aspartate, glutamate receptor) is involved in both the acquisition of fear memory and the induction of long-term potentiation (LTP) in the amygdala. CPP (3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid), a competitive NMDA-receptor antagonist
13 Long-term potentiation (LTP) Lomo, Bliss, Andersen, 1966, Hippocampus. Induced artificially by tetanic stimulation Long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. Increase in synaptic strength A cellular mechanism for learning and memory. Requires protein synthesis Hebbian LTP requires simultaneous pre- and postsynaptic depolarization for its induction ( fire together wire together ) Specificity: to synapse Associativity: associates a weak with a strong input Coopertaivity: weak stimulation of many Spike timing dependent plasticity
14 LA encodes memory independent of fear behavior Ce inactivation
15 Amygdala modulation of memory Hippocampal dependent learning: spatial Striatum dependent-learning: cue-related Morris water maze Injection of d-amphetamine into the Amygdala affects both if right after training, but not if pre-testing Packard, Mcgaugh
16 So, does it encode the memory or just modulates it? It depends.
17 Eyelid (blink) reflex conditioning mpfc Why is trace hippocampal-dependent? Maintaining the CS? Timing the trace? Harder? Eyelid requires ~0.3sec, and hippocampus is required when 0.5-1sec. In tone-shock, trace can be 3sec, and hippocampus is required for ~20sec This suggest context-conditioning
18 Contextual fear
19 Percent Freezing Extinction of fear-conditioning Habit. Cond. Extinction Next Day Trials Sham
20 Extinction: a new learning Faster re-learning
21 Extinction: brain mechanisms mpfc
22 Partial reinforcement extinction effect Partial reinforcement Fixed/variable ratio Fixed/variable schedule Results in longer extinction learning Why? Frustration theory (Amsel): The omission of the US induces frustration. Therefore, during extinction, the frustration predicts the US. Sequential theory (Capaldi): conditioning to strings of NNNRNNNR Bad for behavior flexibility Good for education
23 Aversion Index Garcia J Conditioned Taste Aversion One-trial learning Long-delay learning (few hours) A [lack of] interference effect? Still a problem for neuroscientists Lithium chloride Saline Hedonic shift: changes the CS, not its predictions
24 CTA Compound potentiation: odor + taste increase response to odor Preparedness:
25 Consolidation Anisomycin, a protein synthesis inhibitor, into the Basolateral complex of the amygdala (BLA) No effect on short-term-memory No effect after XX time (rule of thumb is 6hrs) But harms long-term memory below that. CS-US 30m > 24hrs Happy CS-US 8h Scared CS-US 30m Scared CS-US 30m > 24hrs Scared Saline
26 Stress hormones Mcgaugh JL, science, 2000
27 Reconsolidation No effect on STM Nader, Ledoux, Nature 2000
28 An updated view of memories
29 PTSD (post-traumatic-stress-disorder) Extinction failure
30 Reconsolidation and extinction: What Freud always knew... X
31 Context Generalization / specificity
32 Generalization In 1920, Watson and Rayner showed that one-year old Albert feared a rat that was previously paired with banging of steel rail. They then showed that he was afraid of other white fury objects as well. Pavlov, 1927: drooling to similar sounds Stimulus generalization: the behavioral fact that a conditioned response formed to one stimulus may also be elicited by other stimuli which have not been used in the course of conditioning.
33 Categorization Monet Cezanne / Renoir Picasso Matisse / Braque Watanabe, 95
34 Context generalization In fear conditioning, usually performed by training in one chamber, then testing in another. Mainly used with extinction: training in one chamber, extininguished in another. Implications for PTSD. Involves interactions between the amygdala and the hippocampus
35 Stimulus generalization Stimulus generalization on a physical dimension Neurons in many brain areas have tuning curves to a physical dimension Is generalization merely a result of discrimination? Earlier ideas: subjects will generalize to the extent that they cannot discriminate
36 What are emotions? Do we run from a bear because we are afraid, or are we afraid because we run? James proposed that the obvious answer, that we run because we are afraid, was wrong, and instead argued that we are afraid because we run. William James Perception=>bodily changes=>feeling
37 Stay safe, be fearless
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