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Department
Neuroscience
Course
NROC61H3
Professor
Rutsuko Ito
Semester
Fall

Description
Lec05 Learning and memory systems 1. Organization of the brain into multiple, parallel neural systems that mediate different associative memory processes 2. Each of the systems responsible for establishing relationships between specific types of information a. Reinforcement b. Environmental stimuli c. Internal or external responses 3. Dysfunction of any one of the systems may result in a wide spectrum of neuropsychological disorders a. Drug addiction b. Schizophrenia c. Depression d. Eating disorders e. OCD Learning and memory 1. Learning a. Acquisition of new information 2. Memory a. Retention of learned information i. Division into 1. Short term memory 2. Long term memory a. Focus on long term memory Long term memory 1. Further divided into a. Declarative (explicit) i. Episodic 1. Autobiographical ii. Semantic 1. Facts / knowledge of the world b. Non declarative (implicit) i. Procedural 1. How to perform tasks ii. Emotional 2. Each of the different forms of memory are processed in dissociable neural systems a. Hippocampus i. Declarative learning / memory b. Amygdala i. Emotional learning c. Dorsal striatum i. Stimulus response learning ii. Procedural learning (SR) Early evidence for multiple learning and memory systems 1. WHITE study a. Pre-acquisition lesions of the dorsal striatum, hippocampus (fornix) and lateral amygdala b. Training rats on different versions of food foraging on the radial maze c. Investigating the causal roles of these brain regions in processing different types of associative information Radial maze foraging task - Win-Shift 2. Rats trained to collect a single food pellet from the from the ends of each arm of the radial maze 3. Rats allowed to move freely on the maze in each session a. Most effective strategy to enter each arm once 4. Successful performance of this task dependent on a. Learning spatial (extra maze) cues b. Using working memory to track which arms have already been entered 5. Test for: a. Number of errors (re-entry into already visited arm) 6. Results a. Fornix lesioned group made significantly more errors than other test groups i. Control ii. Dorsal striatum lesioned iii. Amygdala lesioned Radial maze foraging task - Win-Stay 1. Lights available at the entrance to each arm to inform the rats about location of food a. Different sets of half the arms (4 of 8) was lit b. Rats allowed the opportunity to collect a pallet from the end of a lit arm twice 2. Successful performance of this task required a. Stimulus (light) - Response (enter arm) association 3. Test for a. Number of errors (visit into unlit arms) 4. Results a. Lesions of the dorsal striatum made more errors than other test groups i. Implication of the dorsal striatum in procedural learning Radial maze foraging task - Conditioned cue preference 1. 2 of 8 arms used 2. Two trials a. Rat confined in empty arm b. Rat confined in arm with large amount of food 3. Associations made a. Empty arm i. Prevented rat from acquiring hippocampus mediated spatial information about arm location ii. Rat never learned to run into the arm to obtain food 1. i.e. never went through SR learning mediated by dorsal striatum b. Food arm i. Association between 1. Environmental stimuli visible from arm 2. Rewarding consequences of eating the food in the food paired arm 4. Test a. When given a choice between the food paired and unpaired arms in extinction (no food) i. Unlesioned rats chose to spend more time in the food paired arm 1. Preference for approaching and remaining in the vicinity of food paired stimuli ii. Only lesions from the amygdala led to deficits in demonstrating a preference for food paired arm 1. Implications in emotional memory Critique of early studies 1. Early studies do not provide conclusive evidence that the three brain regions (hippocampus / amygdala / dorsal striatum) are causally involved in the processes inferred from the studies 2. Limitations a. Electrolytic lesions i. Causes damage to fibers of passage ii. May damage surrounding area as well (non specific) b. Fornix lesions vs hippocampus proper lesions i. Disruption to the fornix (via hippocampal output fibers) is less debilitating in its effect upon spatial learning ii. Compared to lesioning the cell bodies of the hippocampus proper Interacting learning and memory systems 1. Concept of competitive inhibition systems a. Multiple learning and memory systems compete interactively i. E.g. win-stay task 1. Lesion of dorsal striatum actually resulted in better performance compared to control group a. i.e. the removal of one learning and memory system (hippocampus) enhances learning mediated by another system (dorsal striatum) i. Success determined by procedural learning  removal of competitive inhibitor  results in better performance of necessary learning system 2. Concept of dissociable learning and memory systems a. Existence of separate hippocampal and dorsal striatal systems 3. How and where do these interactions take place? a. Research focused on upstream (e.g. prefrontal cortex) and downstream (nucleus accumbens core) of the hippocampus / amygdala / dorsal striatum and their contribution to learning processes Recent evidence of further functional dissociations within dorsal and ventral striatum and evidence that some regions of the striatum and their dopaminergic innervations act as sites of processing regulation Neural systems underlying action vs habit learning 1. AO learning and SR learning occur in parallel a. AO dominates early on in learning (goal directed) b. SR dominates later on during over-training (habit formation) 2. Suggestion that there is a shift in the control of an instrumental, goal oriented performance (AO) to a habitual and automated process (SR) as training progresses a. Evidence suggests that there are two separate neural systems mediating these two forms of learning i. Medial prefrontal cortex ii. Dorsal striatum Medial prefrontal cortex 1. KILLCROSS and COUTUREAU study a. Pre-training excitotoxic lesions of the medial prefrontal cortex i. Two discrete areas had dissociation in AO vs SR learning 1. Prelimbic cortex 2. Infralimbic cortex b. Rats trained to lever press on right (A1) or left (A2) lever for two outcomes (O1 and O2) in two different chambers (S1 and S2) for two different lengths of time (high and low) i. One outcome was devalued (by pre-feeding) ii. Rats placed for 15 minutes in S1 (or S2) chambers, followed by another 15 minutes in the opposite chamber S2 (or S1) iii. Allowed to lever press in extinction c. Results i. Sham group (low training) 1. Selectively reduced responses on lever associated with devalued outcome a. i.e. mediated by AO learning ii. Sham group (high training) 1. Failed to adjust responses to a devalued outcome a. Instrumental responses come under control of SR learning iii. Prelimbic lesioned rats 1. Did not respond with a reduction in responses for devalued outcome in both low and high training conditions a. i.e. prelimbic area implicated in AO learning iv. Infralimbic lesioned rats 1. Showed a reduction in responses for devalued outcome in both low and high training conditions a. i.e. infralimbic area implicated in SR learning Dorsal striatum 1. YIN study a. Conducted pre-training excitotoxic lesions of discrete areas of the dorsal striatum i. Dissociation found between specific areas in AO and SR learning 1. Dorsolateral striatum 2. Dorsomedial striatum b. Trained rats to lever press for sucrose solution i. Under random interval schedules of reinforcement chosen to generate habits ii. Half of the rats 1. Devalued sucrose in home cages using conditioned taste aversion (LiCl) iii. Half of the other rats 1. Injected with saline (no devaluation) c. Test i. All rats put into respective operant chambers for lever pressing in extinction d. Results i. Dorsolateral striatum lesion group 1. Sensitive to outcome devaluation a. Reduced response on a lever associated with sucrose i. Implications in SR learning ii. Dorsomedial striatum lesion group / control group 1. Insensitivity to devaluation a. Implications in AO learning 2. YIN study #2 a. Dorsomedial striatum further tested for role in instrumental learning i. Division into 1. Anterior 2. Posterior b. Rats received 2 separate 30 minute sessions learning to i. Press on one lever for sucrose ii. Press on other lever for food pellet c. One of two outcomes devalued by satiation (feeding
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