Neuroscience of Learning & Memory Midterm

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Ramon y Cajal synaptic plasticity hypothesis

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Ramon y Cajal synaptic plasticity hypothesis

the idea that the strength of a synaptic connection can be modified by experience

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  • during diseases of the brain memories disappear in an orderly fashion

  • old memories are more resistant to disruption

what did RIbot teach us about memory

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recent memories → personal memories → habits, skills → emotional memories

what order do memories disappear according to Ribot

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anterograde amnesia

the inability to acquire new memories

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retrograde amnesia

the loss of memories acquired before the onset of the disease

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Thorndike’s Law of effect

the correct behavior is learned because it results in a successful outcome and strengthens the connection between the stimulus and correct response

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  • storage failure

  • retrieval failure

what are the two explanations for amnesia from Korsakoff

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storage failure

lost memory

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retrieval failure

memory still exists, just can’t access it anymore

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  • initially place rat in a box, play a tone, then follow it with a shock

  • to test context conditioning, place rat in the same box and test freezing

  • to text cued conditioning, place rat in a new box, play the same tone, and test freezing

How can context and cue conditioning be tested separately in rats or mice

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declarative memory

things you know that you can tell others

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non declarative memory

things you know that you can show by doing

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episodic memory

  • any personal experience you may have had, bound to original context

  • remembering your first day of school

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semantic memory

  • independent of original learning

  • knowing the capital of France

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skill learning

knowing to ride a bicycle

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priming

  • exposure to certain stimulus affects later behavior without conscious awareness

  • being more likely to use a word you heard recently

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conditioning

salivating when you see a favorite food

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  • encoding based on relational representations

  • flexibility of representations

  • declarative memory does not depend on awareness during encoding

  • explicit memory retrieval depends on relational representations

describe the updated version of declarative memory

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  • severe anterograde amnesia

  • time-limited retrograde amnesia

  • Intact short-term memory & intelligence

  • severe impairment of declarative memory for new info

  • intact non-declarative memory

  • intact remote memory

what memory functions are impaired or unimpaired in patient HM

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selective hippocampus damage

where was RB’s brain damage

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  • partial impairment of declarative memory

  • severe anterograde amnesia

What memory functions were impaired in RB

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the hippocampus has a relational coding of space

what do the water maze experiments tell us about hippocampus function

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water maze experiment: variable start

train rats on multiple locations, test rat on one location and see if they can still find the location of the hidden platform

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water maze experiment: constant start

train rats on one location, test rat on multiple other locations and see if they can still find the location of the hidden platform

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relational representations of space

how the environment around us goes together and tells us where we are

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place cells

codes for where the animal is in space

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  • external cues help animal tell where it is in the environment

  • different place cells are active depending on the location of the black card

describe the experiments showing the place fields are determined by external stimuli

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grid cells

  • codes a map of the environment more globally

  • grid is the same no matter the environment

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  • training set 1: rat is trained to associate odor A with B and odor X with Y

  • training set 2: rat is trained to associate odor B with C and odor Y with Z

  • test for transitivity: can the rat associate odor A with C and odor X with Z

describe odor paired associates task and the test for transitivity

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  • hippocampus is capable of flexible use of information

  • if the hippocampus is lesioned, unable to have flexible memory

What does the test for transitivity tell us about hippocampal memory.

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  • place cells are also coding for other aspects of the context (color of the wall, smell)

  • place field is determined by what the task is (go west vs go east)

  • neurons code the different situations differently depending on the task

describe the experiments showing context-specific hippocampal activity

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different neurons are active across time

how does the hippocampus code for time

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Tulving’s theory of episodic memory

elements of episodic memory

  • who

  • what

  • when

  • where

autonoetic consciousness

travel forward and backward in mental time

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autonoetic counsciousness

unique to humans, when recollecting an experience able to determine experience occurred to yourself

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Ruby’s theory of episodic memory

  • temporal-spatial context

  • automatic capture

  • pattern completion

  • patter seperation

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automatic capture

brain automatically encode info when experience occurs

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pattern completion

partial information can trigger bringing more info together

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pattern separation

able to separate representations that are similar

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  • patterns of neocortical activity are sent to hippocampal neurons

  • hippocampal neurons store an index of which cortical areas were co-activated

  • temporal-spatial context is automatically captured

describe the indexing theory of hippocampal memory

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  • rat is placed into context A from a circular box

  • rat is then placed back into circular box and is then placed in context B where it receives a shock

  • a fear test is done in context A and context B

  • Rat shows more fear in context A than it does in context B

describe the pattern completion and false memory test

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  • tests rats with rewards adjacent to each other and separate

  • rats with dentate gyrus lesions are unable to find the reward when the open doors are adjacent to each other

describe the pattern separation task and the effects of dentate gyrus lesions

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optogenetics

after opsin genes have been expressed on membranes, they can be activated by light to excite neurons or to inhibit neurons

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  • DOX on, neurons in dentate gyrus not expressing ChR2

  • DOX off, rats allowed to explore context A and dentate gyrus expresses ChR2

  • Rats returned to DOX-on, put in context B and shocked, Blue light stimulation occurred causing an association with Context A

  • Fear test on Context A or new Context C

  • Rats that were exposed to Blue light showed more fear in Context A and little fear in Context C

  • Rats that were not exposed to Blue light show the same amount of feat in Context A and C

describe the experiment of false memories done by Steve Ramirez

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  • DOX on, neurons in CA1 do not express ArchT

  • DOX off, mice experience a fear condition, allows neurons in CA1 to express ArchT

  • Tests for fear conditioning, green light is used to silence neurons expressing ArchT

  • Mice that expressed ArchT and stimulated with the green light did not freeze, but if not stimulated with green light did freeze

Describe the experiment of silencing index neurons in the CA1

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prevents the retrieval of context fear memory

What happens in the cortex when CA1 memory cells are inactivated

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  • memory trace consists of weak neocortical representations, held together by their temporary connections by the medial temporal hippocampal system

  • new memories require MTH system for retrieval

  • as the memory ages, consolidation occurs

  • strengthened connections = retrieved without hippocampus

describe the standard model of systems consolidation

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model shows that damage to the hippocampus results in temporally graded retrograde amnesia

what pattern of results from memory tests supports the standard model system consolidation

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  • both old and new episodic memory always depend on the hippocampus

  • patients with almost complete damage to the hippocampus could not recall either new or old episodic memories

  • some evidence for old episodic memories was found in patients with only partial damage

What was Nadel and Moscovitch’s clinical evidence for the standard model of systems consolidation

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  • during encoding, information about the context is sent to the hippocampus and then to MEC, then the prefrontal cortex and amygdala

  • during recent recall, information about the context is retrieved from hippocampus and then sent to the amygdala

  • during maturation, information about the context is sent to the hippocampus then the MEC, and then the prefrontal cortex

  • during remote recall, information about the context is retrieved from the prefrontal cortex and then sent to the amygdala, leading to a behavior

Describe the Takashi experiment

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systems consolidation for fear conditioning occurs over time

What does the Takashi experiment tell us about systems consolidation

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  • new memories are able to be recalled

  • as memories age, retrieval can degrade memory leading to false contextual detail to memories

  • repetition and replay of memories consolidates connections and creates a semantic memory that can be recalled without the hippocampus

  • episodic contextual detail=requires hippocampus

  • memories lacking contextual detail = does not require hippocampus

Describe Yassa’s competitive trace theory

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  • the memories we are unable to recall have episodic contextual detail and therefore need the hippocampus to recall them

How might Yassa’s theory explain human retrograde amnesia data

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defensive behavioral system

organizes the expression of a variety of behaviors that have evolved to protect us from danger, can be activated by innate danger signals and learned danger signals

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analgesia

less responsive to painful stimuli

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autonomic arousal

increased heart rate, increase respiration, etc.

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predatory imminence gradient

different fear responses dependent on how close a fear stimuli is to an organism

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immediate shock deficit

animal is shocked right away = will show no fear of context

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extinction

  • conditioned stimulus is presented without the unconditioned stimulus

  • conditioned stimulus loses its ability to evoke a conditioned response

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  • spontaneous recovery

  • renewal effect

  • reinstatement effect

what are the three ways to show that extinction is not unlearning

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spontaneous recovery

after a short interval, behavior no longer occurs but after a longer interval, behavior occurs again

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renewal effect

still shows fear for context A despite trying to stop the fear by using extinction in context B

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reinstatement effect

will associate shock with unconditioned stimulus despite it occurring after extinction

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associative loss hypothesis of extinction

extinction is due to presenting the conditioned stimulus alone, which eliminates the association between the conditioned stimulus and unconditioned stimulus

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competing memory hypothesis of extinction

new association occurs between conditioned stimulus with no unconditioned stimulus, which inhibits the occurrence of a conditioned reponse

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  • molecular layer

  • purkinje layer

  • granule cell layer

what are the three layers of the cerebral cortex

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purkinje cell

primary cells, send output out of the cerebellum

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  • sellate cell

  • basket cell

what cells inhibit purkinje cells

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golgi cell

what cell inhibits granule cells

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  • during acquisition, there are strong parallel fiber connections to the purkinje cells which leads to the inhibition of the nucleus, which has weaker synapses

  • eventually, the synapses weaken for purkinje cells, which releases the nucleus from inhibition

  • leads to long-term depression in purkinje cells and long-term potentiation in nucleus

describe Mauk’s theory about the synaptic plasticity mechanisms in the cerebellum that are thought to underlie the memory for eyeblink conditioning

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  • tests for three groups: control group, muscimol injected in cerebellum, muscimol injected in red nucleus

  • during training sessions, only the control group showed evidence of learning the conditioned response

  • after training, both control and red nucleus groups showed evidence of learning

  • cerebellum group did not learn anything

describe the experiment that examined the effect of inactivating the cerebellum or red nucleus on eyeblink conditioning

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  • tests for three groups: two TTX groups, and a control group

  • during training, both TTX groups showed no evidence of learning

  • during testing, all groups had similar percentages of conditioned responses, which indicates learning

describe the experiment that examined the effect of inactivating SCP on eyeblink conditioning

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  • test two groups: muscimol group and control group

  • tested for learning of conditioned and unconditioned responses

  • both tests showed training periods where muscimol group showed no learning

  • both tests showed testing periods where learning of UR and CR is evident

describe the experiment that examined the effect of inactivating the motor neuron on eyeblink conditioning

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indicates memory is stored in the cerebellum because when testing for eyeblink conditioning with cerebellum lesions, during training there was no conditioned responses and during testing there was no savings of what they learned during the training period

What did the results of the inactivation experiments indicate how memory is stored in eyeblink conditioning

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  • the activity in the cerebellum precedes the unconditioned stimulus, therefore it is what leads to a response

  • decrease in purkinje cells leads to long-term depression, LTD & LTP occurring at the same time causes synaptic plasticity

How are changes in neuronal activity in the interpositus nucleus and purkinje cells related synaptic plasticity mechanisms underlying eyeblink conditioning

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  • sensory nuclei

  • pontine nucleus

  • mossy fibers

  • parallel fibers

  • purjinke cells

what is the conditioned stimulus pathway

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  • trangiminal nucleus

  • inferior olive

  • climbing fibers

  • purkinje cells

what is the unconditioned stimulus pathway

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  • purkinje cells will no longer inhibit the nucleus cells

  • after continuous unconditioned and conditioned stimuli, long-term potentiation of the nucleus will occur

  • results in a blink

what happens after long-term depression in purjinke cells

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  • tested for tone and light before the lesion

  • after the lesion, decreased conditioned responses to tone

  • similar percentage of conditioned responses for light as before the lesion

describe the pontine lesion experiment

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pontine nucleus has different areas responsible for different sensory info

what does the pontine lesion experiment tell us

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  • electrical stimulation of mossy fiber + air puff = conditioned stimulus

  • sufficient for learning

  • after lesion of DI, conditioned response is lost

describe the mossy fiber stimulation experiment

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  • pontine lesion experiment

  • mossy fiber stimulation experiment

what two experiments identify the conditioned response pathway for eyeblink conditioning

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  • before lesion, train for conditioned responses

  • after lesion, the conditioned response did not immediately go away, looks like extinction

describe the inferior olive lesion experiment

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  • stimulation of climbing fibers & tone = unconditioned stimulus

  • learning of conditioned responses is normal/ same as control

describe the climbing fiber stimulation experiment

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  • inferior olive lesion experiment

  • climbing fiber stimulation experiment

what two experiments identify the unconditioned stimulus pathway for eyeblink conditioning

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