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week 9

by: Emma Notetaker

week 9 NSCI 4510

Emma Notetaker
GPA 3.975

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week 9 of lecture notes
Biological Psychology
Dr. Colombo
Class Notes
25 ?




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This 6 page Class Notes was uploaded by Emma Notetaker on Thursday March 10, 2016. The Class Notes belongs to NSCI 4510 at Tulane University taught by Dr. Colombo in Spring 2016. Since its upload, it has received 19 views. For similar materials see Biological Psychology in Neuroscience at Tulane University.

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Date Created: 03/10/16
Monday, March 7, 2016 Week 9 Research Articles • Differential Immune System DNA Methylation and Cytokine Regulation in Post-Traumatic Stress Disorder • DNA methylation: adding a methyl group way to measure DNA regulation • • DNA neatly coiled around histones • in order for gene to be expressed, have to physically expose portion of molecule which can bind to promotor • experiential regulation AND inherited • usually decreases gene expression epigenetic changes: don’t affect actual sequence of nucleotides, but alter expression of • genes (methylation is an example) • PTSD: due to exposure to traumatic events • symptoms: intrusive memories, thoughts and feelings • hyperarousal • anxiety cytokines: signal in neurocrine system - act like neurotransmitters • • not genes - actual molecules • CpG sites: bases that are in line with each other • hypothesis: exposure to traumatic events (childhood trauma or later in life) may cause epigenetic changes to DNA, which may alter behavior • DNA methylation may mediate persistent changes in the functioning of genes after chronic stress • childhood trauma OR high levels of lifetime cumulative stress will result in changes in DNA methylation • plasma cytokine levels will be associated with PTSD • chronic stress changes immune dysregulation • differentially methylated CpG sites over represented in genes related to immune function and inflammation • relationship between stress levels and development of PTSD • psychological stress may change the DNA methylation patterns (from immune dysregulation due to stress) • methods: • correlational study - no intervention administered PTSD scale - people who are clinically trained asses the subjects • • instrument administered by clinician • questionnaire asking about exposure to childhood trauma • took blood sample from periphery (not in the brain) • may or not be related to brain’s blood (due to BBB) • split into 4 groups based on PTSD and child abuse PTSD patients vs. control group • • measured total life stress (TLC) • results: • beta value: measure of methylated vs. un-methylated CpG sites • greater beta value indicates higher methylation 1 Monday, March 7, 2016 • overall: PTSD patients have higher levels of global methylation in the genes of their peripheral blood this technique is very touchy: amazing because you can look at so many genes, but so • much data that it is VERY difficult to interpret • in this study - the ones examined demonstrated the largest changes • differently methylated in several areas - seems that the genes that showed the biggest changes in methylation have to do with stress/immune response • some go down in PTSD while some increase translocated promotor region (TPR) decreased in methylation with PTSD • • TPR interacts with glucocorticoid receptors (measures main stress hormone) • CLEC9A increased • associated with immunoreceptor (immune response) • ACP5 increased • phosphatase (removes phosphate groups) stops short term plasticity • • ANXA2 decreased • TLR increases • related to stress • total life stress plotted against methylation • lowest levels of methylation associated with the highest life stress TNF alpha: cytokine • • stimulates HPA axis • pro-inflammatory response • increased with total life stress - inflammation increases with stress • cytokine levels more associated with total life stress • methylation levels more associated with PTSD • Brain response during visual emotional processing: an fMRI study of alexithymia • alexithymia: inability to recognize/describe emotions (issues in emotional processing) • process emotion differently, cannot understand different emotions • in 10% of general population • previous studies have shown inconsistencies in brain areas associated with alexithymia • hypothesis: altered function in anterior cingulate cortex implicated in alexithymia • methods: • behavioral intervention • subjected to emotional stimuli and measured brain activity • independent variable: nature of the emotional stimuli • dependent variable: brain activity • emotional stimuli: pictures (2 scales) • positive or negative • high or low intensity • only used females • some gene differentiation between male and females • now NIH has requirement that you use both genders unless there is a good justification • groups of 15 (high and low alexithymia) • scale measured Alexithymia (had to test 432 females to get the 30 subjects) • took people that tested very low and very high • also self-rates anxiety/depression questionnaires - tried to minimize levels of anxiety and depression (controlled for this) 2 Monday, March 7, 2016 • used fMRI to monitor brain activity in: • ACC mPFC • • insula • temporal lobe • took a baseline • results: • with negative high intensity stimuli: less activation in temporal, frontal and ACC with high-alexithymic • • positive high intensity stimuli: • MORE activation in frontal, precentral and insular gyro with high-alexithymic • mostly associated with cortex • **increase in lentiform/putamen** (different memory system - part of basal ganglia) • positive low intensity stimuli: more bilateral activity in ACC with high alexithymic • • both high and low alexithymic subjects showed similar activation in these areas with neutral stimuli • alexithymic group associated with increases of depression and anxiety • very few changes in the activity of the limbic system (except ACC) with these differences mostly cortical differences - people with alexithymia seem to have issues with • cortical processing of the information that is processed in the limbic system • cortical interpretation (reported subjective feeling) amiss • limbic components are assembling emotional stimuli, which seem to remain unaffected • positive and negative are not the same!! interpretation involves different brain areas Memory Systems • opposing theories memory is property of cells - everywhere in the brain • • memory stored in specific locations (localized) • working memory is NOT short term memory • get rid of it once you complete task - time varies • ex: have to remember where you parked • HM: bike accident - debilitating seizures localized in hippocampus (excited primarily by glutamate) • • hippocampus especially sensitive to excitation • surgeons removed medial temporal lobe (bilaterally) • removed hippocampus and amygdala • HM awake for this • no change in IQ, intellect intact lost ability to form ANY new memories (global anterograde amnesia) • • lost EPISODIC memory (declarative/explicit) • if asked who the president was, would say it was whoever was president before his accident • lost ability to be trace conditioned • normal short term memory, could carry out conversation 3 Monday, March 7, 2016 • this area deemed the first memory system (in 1957) due to his case • subjected to many tasks testing his intact skills mirror tracing: motor skill learning • • got better and better as he learned - remembered from day to day • RETAINED ability to learn motor skills • suggests that hippocampus is not the only area of the brain where memory resides • word-stem completion task: priming • exposure to information, then fill in the end of words amnesics do just as well, if not better, than controls with word completion • • medial temporal lobe removal: can still store information, just not in explicit fashion • with priming, there is a decrease in activity in brain areas - brain operates more efficiently • classical conditioning: paired tone with air puff into the eye • people start to associate tone with blinking delay conditioning: delay between onset of tone and onset of air puff • • tone stays on throughout duration, still on when air puff comes • CAN be learned with medial temporal lobe amnesia • trace conditioning: tone still before, but leaves before air puff • medial temporal lobe amnesics CANNOT be trace conditioned • intact skills: learning motor skills • • priming • delay conditioning (simple classical conditioning) • medial temporal lobe amnesia (mostly hippocampus) • impaired: • declarative memory • episodic: events of your life • semantic: facts • dissociated from time and place - don’t always know where/when you learned it • probably stems from episodic memory • intact: • nondeclarative (procedural memory) • skill learning • priming • conditioning (simple - delayed) • time courses of memory - 2 kinds of memory storage • extent of the two very variable • short tem • rapid • no structural change - in terms of neural activity • labile - unstable • strength decreases with time • occurs first • long term • slow • building new synapses - structural changes • strength increases with time • stable • occurs after short term 4 Monday, March 7, 2016 • recall test: • controls recall more items from beginning (primacy effect) and end (recency effect) of the list - forget most from the middle • end of the list still in short term memory • things from beginning of the list have started to be consolidated to long term memory • amnesics remember things from the end, NOT from the beginning • because their long term memory is the issue • if no delay, ONLY recency effect with intermediate delays, get primacy and recency effect • • with VERY long delay, no recency effect (only primacy) • most recent items have not been in long term, while the rest have • too long to still use the short term memory • animal models of amnesia: hippocampal damage in rats • normal (or better than normal) acquisition of standard (Skinner) operant conditioning tests conflicting findings with spatial and sensory discrimination tasks • • y maze: sensory discrimination • simultaneous visual discrimination (see both black and white) • one arm is black, one is white • one color will be rewarded - rat learns which one it wants • rewarded arm switches positions after delays - seeing if they will choose the correct color for reward • INTACT with hippocampal damage • other y-maze task: SPATIAL discrimination task • concurrent visual discrimination (see EITHER white or black, never both together) • rat will see two black or two white inserts • if white, have to turn left • if black, have to turn right • IMPAIRED with hippocampal damage • found that hippocampus important for SPATIAL memory • water maze task: spatial navigation (Morris) • hidden platform in opaque water - rat has to find it • started from different locations, but platform remains in the same location • place navigation: have to find the platform (that remains in the same place) • normal animals learn rapidly over the first few trials - takes shorter time to get to it with repeated studies • lesioned cortex: no effect • lesioned hippocampus: NEVER do as well as controls • cue navigation: put something else to cue where the platform is (platform may move) • rats with lesions of cortex and hippocampus so JUST as well as controls • showing that they are able to swim to cue shows that they’re still motivated, motor skilled and able to process sensory information • probe trials: move platform • cortical lesion and controls spend more time looking where the platform used to be • lesioned hippocampus spend equal time in each quadrant - do not remember that the platform was in a specific location • conclusions: • hippocampus has nothing to do with vision, motivation, motor skills • hippocampus is related to spatial navigation 5 Monday, March 7, 2016 • lesions to hippocampus can still have decrease in latency, but don’t have spatial bias Olton: hippocampus NOT necessary for spatial memory, but working memory • • critique of Morris - not all spatial memory impaired (reference memory intact, working memory impaired) • radial arm mazes: animal placed in center, food placed in separate arms • A. once baited arms: optimal performance means going in each arm once • tests working memory (have to remember which arms you’ve visited) only want to remember this for a day - irrelevant for next trial (have to start over) • • hippocampal lesions caused IMPAIRMENTS (spatial memory task) • B. reference memory task • some arms baited, some NEVER baited • now animal has to learn to go to the baited arms and not go to the ones without bait hippocampal lesions could still remember reference memory (knew which ones • never had food), but struggled with working memory (knowing which ones they’d been to already) • C. working memory task - each arm a different texture • NON spatial working memory task • move order of textures every day go in each texture only once per day • • hippocampal lesions IMPAIRED • shows that not spatial memory that is impaired, but working memory • however, reference memory was impaired in the Morris task…inconclusive • some evidence supports each hypothesis • inferential memory expression - not spatial • Eichenbaum • animals learn paired associates (hippocampal lesions are still intact - can still learn simple associations) • odors paired with other odors • if given A, food reward paired with B (not with Y) • if given X, food reward paired with Y (not with B) • then go to another set • given B go to C • given Y go to Z • test for transitivity: • given A: see if they go to C (because A—>B—>C) • given X: see if they go to Z (because x—>y—>z) • SEVERELY impaired with hippocampal lesion (controls are fine) - cannot learn the rule • summary: • 1. various kinds of learning, spatial, non spatial, simple and complex can be accomplished WITHOUT the hippocampus in animals and human amnesics • 2. hippocampus REQUIRED to link representations of overlapping experiences into a relational representation • necessary for flexible and inferential expression of indirect associations among items within larger organization of linked memories 6


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