Learning and Memory

  • What is learning and memory?

    • Learning: changes in the brain as a result of experience

      • Facts, events, skills, and behavior patterns 

    • Memory: ability to store and retrieve the changes 

  • Different types of memory and learning

    • Short-term: seconds → hours (<24)

      • Limited capacity 

    • Long-term: ~24 hours → ??

      • Virtually unlimited capacity 

    • Working memory: information that is temporarily stored while we using it

      • Requires focused attention 

  • Patient H.M. – know his case and where damage is

    • 27 years old in 1953 

    • Severe epilepsy following a childhood head injury 

    • Seizures arouse from the medial parts of H.M. temporal lobes 

    • H.M. underwent a bilateral medial temporal lobectomy to relieve his symptoms 

      • Removed most of hippocampus, amygdala, adjacent cortex 

    • Results: 

      • Seizure almost completely eliminated 

      • Devastating amnesia (pathological memory loss) 

    • Things he could do vs things he could not

      • Explicit memory impaired 

        • Remote memory intact 

        • Recent episodic memories were impaired 

        • Could not form new semantic or episodic memories 

          • Could not perform explicit memory task (digital span and block-tapping task) 

      • Implicit memory intact

        • Could learn new movement patterns, motor skills, and classical condition 

        • New implicit memories retained 

          • Perform well on implicit tasks (mirror tracing and incomplete pictures task)

  • Medial Temporal Lobes – functions, how we test

    • Hippocampus

      • Greek for seahorse 

      • Evidence from humans and animals points to role in spatial memory 

        • Memory for places, locations of objects, spatial navigation abilities 

      • Tests; 

        • fMRI studies indicated increased hippocampal activation when people perform spatial tasks 

          • London taxi driver study (2000)

            • experienced drivers have larger posterior hippocampi than non-drivers 

            • Size was positively correlated with number of years on the job 

          • Follow up study (2011) on cabbies in training 

            • Before training: no difference in hippocampal volume 

            • After training: 3 groups 

              • Trainees who passed (39) 

              • Trainees who failed (32) 

              • Controls (31) 

    • Rhinal cortex (tissue surrounding the hippocampus)

      • Perihinal cortex, entorhinal cortex, parahippocampal cortex 

      • Important input to hippocampus for spatial memory and object recognition memory 

      • Test: 

        • DNMS Task/Mumby Box 

        • Novel Objection Recognition Test

    • Amygdala

      • Strengthens emotionally significant memories stored by other areas 

  • Place cells and grid cells

    • Place cells are many hippocampal neurons 

      • Fire action potentials during navigation of a familiar environment 

      • Different groups of place cells fire in different locations

    • Grid cells found in the entorhinal cortex 

      • Fire at regular intervals as animals navigates an open area 

      • Hexagonal “firing fields” help the brain form an internal map of coordinates 

  • Tests learning and memory in other animals

    • Hippocampus:

      • Morris water maze: rats learn to find a hidden platform in a murky pool of water 

        • Visual cues around the room signal location or platform 

        • Starting point is changed in each trial 

      • Radial arm maze: rats learn to remember which arms contain food 

        • Must learn not to visit arms without food or revisit arms where they got the food 

      • Rodents with hippocampal lesions perform poorly on both tasks 

    • Rhinal Cortex: 

      • DNSMS Task/Mumby box: 

        • DNMS = delayed nonmatching to sample 

          • Used in nonhuman primates 

          • Monkey shown an object → delay → choice of 2 objects 

          • Reward is underneath the unfamiliar object 

        • Adapted for rats using the Mumby box 

        • Animals with rhinal cortex lesions are severely impaired 

      • Novel Object Recognition Test 

        • Rodent task that has largely replaced DNMS

        • Phase 1: Animal placed in area with 2 identical objects 

        • Delay: 45 min ~ 1 hr or more 

        • Phase 2: animal placed in area with 1 object from Trail 1 (familiar) and 1 new object (novel) 

        • “NOR score” = time spent exploring novel - time spent exploring familiar 

        • Perianal cortex lesions impair performance 

  • Areas other than MTL

    • Inferotemporal cortex

      • Ventral portion of temporal cortex (outer surface of temporal lobe) 

      • Stores visual memories 

      • Fusiform gyrus: important for facial recognition 

    • PFC and working memory

      • Most rostral (anterior) portion of the frontal lobe 

      • Important for working memory 

      • Delayed response task: 

        • Present a stimulus → delay → make response 

        • PFC neurons are active during the delay

    • Striatum

      • Part of the basal ganglia

        • Caudate nucleus and putamen  

      • Formation and storage of memories about relationship between stimuli and responses 

      • T maze used to test habit formation in rodents 

    • Cerebellum

      • “Little brain” in the metencephalon of the hindbrain

      • Simple forms of associative motor learning

        • Eyeblink conditioning:

          • air puff (US) → blink 

          • air puff (US) + tone (CS) 

          • tone (CS) → blink (CR)

      • Neural plasticity in cerebellum linked to motor skill learning 

  • Hebb’s Theory

    • Axon of neuron A repeatedly stimulates receptors of dendrites of neuron B

      • In the future, A is more likely to excite B because the connection between A and B has strengthened 

      • “Cells that fire together wire together” 

    • Memories are stored in cell assemblies (networks of connected neurons)

  • LTP and glutamate – NMDA receptors

    • LTP shown to depend on changed at synapses that release glutamate 

    • Activation of NMDA-type glutamate receptors is critical 

    • NMDA receptors cause other proteins to be activated, leading to maintenance of LTP 

    • “Doogie” mice – what is special about them

      • transgenic mice born with higher numbers of NMDA receptors 

        • Superior learners at a young age 

  • Alzheimer’s

    • Protein tangles – what are they? Why are they controversial in treatment?

      • Amyloid plaques surround and destroy neurons 

      • Tau tangles form inside neurons and destroy their internal structure

    • Progression in the brain – why is it so hard to treat?

      • Pathology starts in MTL, spreads throughout cortex 

      • Symptoms don’t appear until many years after plaques/tangles start forming 

    • Deficits

      • Deficits in implicit memory for verbal and perceptual material 

    • Risk and protective factors

      • Genetic factors 

      • Non-genetic factors 

      • Environment and aging