Conditioning and Learning Test 2 Part 2 6 25 15 Memory Modulation cont experimental evidence When a learning experience occurs there are 3 parallel effects facts from consolidation Neocortex emotional memory amygdala and consolidation adrenal glands o But we were focusing on consolidation through epinephrine adrenal glands When Norepinephrine NE is injected the Morris Water Maze shows that after a day the rats are able to find the platform faster the reverse result is shown with propranolol an inhibitor o We can apply these findings to the inhibitory avoidance task the rats show a huge response to a weak shock when NE is applied and a small response to a strong shock w propranolol There is a positive relationship b t amount of NE and strength of shock this can be manipulated to affect memory the opposite is the case with propranolol Can you increase NE w o a drug that enhances it o You can use microdialysis a method for collecting neurochemicals in the brain to find out if this is possible if something makes NE get sent out the tubing can measure it Looking at Inhibitory avoidance in particular when shock was delivered higher the shock the more NE it really only has this effect when senses are heightened for curiosity s sake For example getting shocked in an unfamiliar environment In either case the strength of the shock is correlated with the strength of consolidation o This shows how important unexpected events are for consolidation curiosity helps memory Now that we know what NE can do and how to measure it how is the Amygdala involved in the overall process How does it modulate the signal and affect NE o Biological Breakdown While exploring and curious an arousing vent activates the sympathetic nervous system causing adrenal glands to release E and glucocorticoids Epinephrine binds to the vagus nerve as a relay the vagus nerve transmits a signal into the salivary tract to activate C1 neurons which activate Locus Coeruleus neurons This is then conveyed to the amygdala as the release of NE at approximately the same time glucocorticoids invade the BLA region of the amygdala The amygdala s anatomical connections then allow it to influence other regions to the cortex hippocampus entorhinal cortex and basal ganglia o There is also an experiment that deals specifically with the connection between the amygdala and hippocampus McIntyre et Al 2005 trained rats w a cannula inserted into the brain that delivered either a drug or control amygdala activation regulates ARC protein expression in the hippocampus We measure ARC proteins as a proxy for hippocampus stimulation through lidocaine antagonist and clenbuterol agonist the idea being that as NE increases in BLA there is an increase in hippocampal activity In the inhibitory avoidance task those w lidocaine jump immediately back to the dark half and w clenbuterol they took longer because the memory became a strong one Imagine the BLA like a control knob for the hippocampus o Summary of the Modulation Pathway Adrenal Glands BLA Neurons BLA projects broadly to regions of the brain to store memories may modulate memory storage by regulating hippocampal activity increase in ARC protein Side note Norepinephrine can have direct effects on hippocampus helps us to continue the idea that the more arousing a learning experience is the more hippocampal activity can result o NE in hippocampus phosphorylates AMPA receptors in the region making them work better with more sodium in the cell What else can the Amygdala do other than modulate memory signals o Patient S M had a disease related lesion of the sublateral area of the amygdala and some adjacent damage to the entorhinal cortex Had normal everything other than processing of emotional material not aroused from stimuli does not show normal conditioned fear responses and social behavior was indiscriminately trusting These issues were related to the inability to identify far from facial expression when looking at fearful faces S M avoided the eyes which convey the greatest extent of fear They didn t know if this was a motor problem or the learning performance distinction at play When instructed to look at eyes she was as good as the control group at identifying a fearful state The amygdala may not be the central fear cortex but it IS related to processing fear stimuli o Patient T N became cortically blind after damage to the occipital lobe no conscious experience of vision but visual info still got in However fMRI showed right amygdala activation when presented w a face o These together are further evidence that the amygdala plays a role even when cortically showing a direct gaze blind Reconsolidation 6 25 15 There are other ways to modulate memory and memory strength besides epinephrine or use of drugs and they may actually be better more robust o One example is the set of Lewis Experiments from 1968 use of tone shock pairings over 2 days on rats showing that reactivated fear memories are vulnerable to disruption by ECS measured in the amount of time frozen after hearing the tone latency response All groups had the original conditioning with the tone shock pairings on the first day it was the second and third day that set groups apart 4 groups One group had no reactivation or ECS another group just had ECS w no reactivation Results showed ECS alone will not degrade memory One group got a single presentation of only the conditioned tone on the second day for reactivation of memory and then was tested again 24 hrs later no ECS The last group had this reactivation as well as ECS right after and they were the only one out of the 4 not showing normally conditioned responses after the 2 days the memory of the shock was essentially lost no response to the tone o The above experiment gave the origin of the Active Trace Theory memories can exist in either an STM active state or in an LTM inactive state This binary existence shows up with both new experiences and in retrieval of existing LTM trace calling on something already learned disruption affects both All memory traces become inactive with time and in an inactive state they are less vulnerable to disruption when just given time they are harder to disrupt o We can also look at this Lewis Effect in humans the trace still shows vulnerability In this version subjects were human patients already receiving ECS for Major Depression groups were exposed to 2 different slide shows of strong emotional content prior to ECS and then tested on strength of memory