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 Classical fear conditioning Percent Freezing Habit. Cond. Extinction 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
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 Extinction of fear conditioning Percent Freezing Habit. Cond. Extinction
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 Garcia J Conditioned Taste Aversion One trial learning Long delay learning (few hours) A [lack of] interference effect? Still a problem for neuroscientists Aversion Index 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 Stay safe, be fearless
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