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Mundy et al. Hypothesis Q: Do the Hippocampus and Perirhinal Cortex contribute to different types of perceptual learning? Hypothesis 1. The Hippocampus has a more selective involvement in learning about scenes 2. The Perirhinal Cortex has a stronger involvement in learning about faces Participan...

Mundy et al. Hypothesis Q: Do the Hippocampus and Perirhinal Cortex contribute to different types of perceptual learning? Hypothesis 1. The Hippocampus has a more selective involvement in learning about scenes 2. The Perirhinal Cortex has a stronger involvement in learning about faces Participants N=2 HC3 = bilateral HC damage MTL3 - bilateral MTL damage (including HC and PrC) N = 16 healthy participants Trained and tested as in study 1 (exposure followed by discrimination testing) Methods Combine two techniques to verify whether MTL selectively encodes domain-specific visual information (scenes vs faces): 1) Test patients with focal lesions of the MTL (causal) 2) Use fMRI (BOLD) approaches to determine whether the brain regions encode information in a domain-specific manner (correlational) fMRI: Neural activity is estimated through a Blood Oxygenation Level Dependent (BOLD) signal - a measure of cerebral blood flow - Q: Are brain areas sensitive to faces and scenes modulated by 1) exposure history (Experiment 2A) 2) discrimination accuracy (Experiment 2B) fROI: functional region of interest (pre-identified regions to look at) Face encoding region = FFA Scene encoding region = PPA ◦ MTL Regions: ◦ Perirhinal Cortex (PrC); ◦ Anterior Hippocampus(AntHC); ◦ Posterior Hippocampus (PostHC) Results EXPERIMENT #1 Discrimination: The greater the difference, the greater the perceptual learning effect  Controls equally discriminate pre-exposed from nonexposed stimuli for each stimulus domain HC3 shows disruption in discriminating pre-exposed from nonexposed SCENES MTL3 shows disruption in discriminating pre-exposed from nonexposed FACES & SCENES RT: No difference in RT between pre-exposed and nonexposed stimuli for controls across all stimulus type HC3 took longer to respond to SCENE stimuli MTL3 took longer to respond to FACE & SCENE stimuli Controls show an improved performance across Blocks for each stimulus type HC3 shows improved performance across Blocks for DOTS & FACES but not SCENE MTL3 shows improved performance for DOTS, but not FACES and SCENE EXPERIMENT #2 2A - No differences in discrimination accuracy between stimulus types Participants do better in discriminating pre-exposed stimuli vs non-exposed 2B - Greater activity to pre-exposued than to non-exposed face pairs in FFA No modulation for scenes and dot - Greater activity to pre-exposued than to non-exposed scene pairs in PPA No modulation for faces and dot - No difference in RTs to same and different pairs - no response bias - PrC = discrimination accuracy for faces (not scenes) - PostHC = discrimination accuracy for scenes (not faces) - AntHC = no association with discrimination accuracy (faces or scenes) Waelti et al. Hypothesis Q: are dopamine signals fully consistent with reward prediction errors? Hypothesis: The prediction error signal in temporal difference reinforcement learning Participants - Monkeys - Within subject, comparing same neuron within one animal Methods - 4 visual stimuli: A,B, X,Y - 4 phases 1. A+ juice (A > CR) 2. B+ no juice (B) 3. AX + juice (A+X > CR) 4. BY+juice (Y > CR) Results - anticipatory licking is present to A and AX but not to X during the test - No anticipatory licking to B - Anticipatory licking to BY (because it was paired to juice) - Anticipatory licking to Y during the test Phase 1 & 2: - A = dopamine response to CS - A = dopamine dip when reward not presented - B = no response to CS - B = dopamine activity to unexpected reward Compound Phases: - AX = dopamine response to A+X - BY = increasing dopamine response to B+Y Test Phase: - X = response to CS (but less than Y) - X not presented = no change in response - Y = increased response to CS - Y not presented = dopamine dip Unexpected rewards = Prediction error signal = increase in DA activity Omitted reward = negative prediction error = decrease in DA activity Expected reward = no prediction error = no change in DA activity Steinberg et al Role of reward-prediction errors (RPE) RPE = Actual Reward - Expected Reward - Positive RPE: strengthens cue-reward associations - Presentation of an unpredicted reward or reward better than expected - Negative RPE: weakens cue reward-associations - Leads to extinction - Expected rewards omitted - No RPE: when expected rewards is expected and presented Hypothesis Dopamine activity acts as a teaching signal, influencing learning about antecedent cues Participants Methods Optogenetics: artificially mimic a RPE by stimulating DA neurons Behavioural: 1. Blocking: inability to learn an association between a new stimulus (B) and a reward (US) if another stimulus (A) can already reliably predict the reward 1. No expectation of reward 2. Extinction: no reward 1. Downshift: less salient reward (slower extinction, reduced negative RPE) 2. Total extinction: no reward Results Downshift extinction task: Dopamine neurons in the VTA showed reduced firing in response to a downshift in reward (less than expected), reflecting a negative prediction error Optogenetic inhibition of dopamine neurons during the downshift event impaired the ability to extinguish learned behaviours, suggesting that negative prediction errors are critical for extinction learning Optogenetic activation of dopamine neurons during a non-rewarded trial (mimicking a positive prediction error) enhanced learning of an association between the stimulus and reward, demonstrating the importance of positive prediction errors in reinforcement learning Phasic dopamine signals were shown to be causally linked to the learning process, with their manipulation (inhibition or activation) affecting the ability of animals to learn from changes in reward expectations Dopamine neuron activity during unexpected reward omission (negative prediction error) was necessary for adjusting behavior in response to reduced rewards, confirming a link between dopamine firing and the updating of reward expectations Animals with dopamine neuron inhibition during reward prediction errors (both positive and negative) showed significant deficits in learning from changing reward contingencies. McNally et al. Fear acquisition: Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US) = Tone + Footshock = Freezing ; Extinction: extinction of the freezing conditioned response (CR) elicited by the CS via nonreinforced presentations of the CS = Tone + No footshock = Reduction in freezing Hypothesis Q: How would opioid receptor manipulations in the PAG affect fear extinction via injections of naloxone, an opioid receptor antagonist? The PAG may be crucial for fear extinction of conditioned freezing Methods EXPERIMENT #1: ROLE OF OPIOID RECEPTORS IN VLPAG IN ACQUISITION AND EXPRES- SION OF FEAR EXTINCTION To determine whether a similar impairment of extinction would occur when the effects of naloxone were restricted to the vlPAG EXPERIMENT #2: ROLE OF VLPAG OPIOID RECEPTORS IN EXTINCTION OF CONDITIONED FEAR 1. To confirm the reliability and extend the generality of the impairment of fear extinction by using a different set of parameters for CS exposures during extinction Rats received eight 2 min CS presentations (vs 1x 10 min in Exp. 1) 2. To determine whether any impairment of extinction of the freezing CR produced by vlPAG infusions of naloxone would be manifest during a drug-free test Rats received 2 days of extinction (Vs 5 days of extinction in Exp. 2), which did not produce complete extinction of freezing and were then tested for freezing to the CS EXPERIMENT #3: ROLE OF DPAG OPIOID RECEPTORS IN EXTINCTION OF CONDITIONED FEAR Same as Exp 1, but microinjections were in the dlPAG EXPERIMENT 4: DOSE–RESPONSE PROPERTIES OF VLPAG OPIOID RECEPTOR CONTRIBUTIONS TO EXTINCTION OF CONDITIONED FEAR Same as experiment 2 but but rats received microinjections of 5, 0.5, 0.05, 0.0 g of naloxone Results Experiment #1 microinjections of naloxone into the vlPAG impair the extinction of Pavlovian fear conditioning. However, these microinjections did not reinstate expression of already extinguished CR 𝛍  microinjections of naloxone into the PAG impair the development but not the expression of extinction of conditioned fear There was a difference between the naloxone and saline groups during the first 4 min of the CS on day 1 of extinction: naloxone animals displayed significantly more freezing than the saline animals in the first 4 min Experiment #2 microinjections of naloxone into the vlPAG impair the extinction of a freezing CR and also show that this impairment is manifest during a drug-free test Experiment #3 microinjections of naloxone into the dPAG do not impair the extinction of Pavlovian fear conditioning as indexed by freezing confirmed the neuroanatomical specificity of vlPAG opioid receptor contributions to the extinction of conditioned freezing Experiment #4 the effects of naloxone on fear extinction were dose-dependent: As the dose of naloxone infused into the vlPAG before extinction training increased, so too did the amount of freezing subsequently displayed on the drug-free test Likthik et al Fear conditioning: BLA + > CeA = fear expression Fear extinction: BLA + > ITC - > CeA = inhibition of fear expression Hypothesis Disruption of the ITC neurons would impair the expression of fear extinction, leading to the persistence of fear responses even after extinction training. Participants Rats placed in 3 groups: Group 1 (experimental): D-Sap infusions to lesion ITC cells target ITC clusters between BLA and CeA Group 2 (control): U-Sap infusions (no effect on ITC) Group 3 (control): D-Sap infusions in BLA or CeA (no effect on ITC) Methods Day 1: habituation Day 2: fear acquisition = tone + foot shock Day 3: extinction = tone w/o foot shock in new setting Day 4: ITC lesion Day 11: recall test  Measurements Differences in immunoreactivity of ORs Freezing times (in percentage) under different toxins Correlation between number of surviving ITC and freezing behaviours Results ORs are most concentrated in ITC cells vs other subregions Immunoreactivity primarily on post-synaptic sides (i.e. connection between ITC & CeA) Siginificantly less ITC neurons in experimental group = D-Sap targets ITC ITC lesion did impair extinction of fear All groups acquired fear in new context = ITC not involved in acquisition Strong inverse correlation = fewer ITC correlate with fear responses not shown in CeA 𝛍 𝛍