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Cil Flores
Regina Munoz
   Kim Ocana
   Monkeys with bilateral medial temporal
    lobectomies have major problems forming
    long-term memories for objects encountered
    in the delayed nonmatching-to-sample test.
   Intact , well-trained monkeys performed
    correctly on about 90% of delayed
    nonmatching-to-sample trials when the
    retention intervals were a few minutes or less.
   In contrast, monkeys with bilateral medial
    temporal lobe lesions had major object-
    recognition deficits.
100

 80

 60
                                             Medial temporal lobe
 40                                          lesions
                                             Normal controls
 20

 0

        8       15      1 minute     10
      seconds seconds              minutes
   The development of the delayed nonmatching-to-
    sample test for monkeys provided a means of
    testing the assumptions that the amnesia resulting
    from medial temporal lobe damage is entirely the
    consequence of hippocampal damage.
Aspiration lesions of
   the hippocampus in
     monkeys and rats.
Because of differences
         in the size and
         location of the
       hippocampus in
        monkeys and in
rats, hippocampectom
y typically involves the
       removal of large
     amounts of rhinal
               cortex in
   monkeys, but not in
                    rats.
   Mumby box
     David Mumby
     Delayed nonmatching-to-sample test for rats
     It was assumed that rats could not perform a task
      as complex as that required for the delayed
      nonmatching-to-sample test.

    Combined bilateral lesions of rats’
     hippocampus, amgdala, & rhinal cortex produce
     major retention deficits at all but the shortest
     retention intervals.
   Hippocampal lesions consistently disrupt the
    performance of tasks that involve the
    memory for spatial location.
   Morris water maze test
    ◦ Rats with hippocampal lesions learn the task with
      great difficulty.
   Radial arm maze test
    ◦ Intact rats readily learn to visit only those that
      contain food, without visiting the same arm more
      than once each day.
   Radial arm maze test
    ◦ Reference memory-memory for the general
      principles and skills that are required to perform a
      task
    ◦ Ability to visit only the baited arms of the radial arm
      maze.
    ◦ Working memory-temporary memory that is
      necessary for the successful performance of a task
      on which one is currently working.
    ◦ Ability to refrain from visiting an arm more than
      once in a given day
    ◦ Rats with hippocampal lesions display major
      deficits on both ref. & working memory.
   Place cells
    ◦ Neurons that respond only when a subject is in
      specific locations.
    ◦ By placing a rat in an ambiguous situation in a
      familiar test environment, it is possible to
      determine whether the rat thinks it is from the
      route that it takes to get to the location in the
      environment where it has previously been rewarded
   Species of birds that
    remember where
    they store seeds have
    larger
    hippocampuses than
    birds that do not
    store
    seeds, supporting
    the idea that
    hippocampus is
    important for spatial
    memory in many, if
    not all, species.
   Experiment with humans in virtual-reality
    towns (show activity in hippocampus using
    positron emission tomography, PET) and with
    taxi drivers (bigger hippocampuses measured
    with magnetic resonance imaging, MRI) also
    support this idea.
   Cognitive map theory
    ◦ O’Keefe and Nadel
    ◦ There are several systems in the brain that
      specializes in the memory for different kinds of
      information, and the specific function of the
      hippocampus is the storage of memories for spatial
      location.
Brown and Aggleton
Theory of the role of hippocampus in object
  recognition that emphasizes its relation to the
  perirhinal cortex.
◦ Perirheral cortex, not the hippocampus, plays a key
  role in most object-recognition tasks.
   Configural association memory
    ◦ Based on the premise that spatial memory is one
      specific manifestation of the hippocampus’s more
      general function.
    ◦ Hippocampus plays a role in the retention of the
      behavioral significance of combinations of
      stimuli, but not of individual stimuli.
   Inferotemporal Cortex
    ◦ The cortex of the inferior temporal lobe
    ◦ Involved in the perception of objects, it is thought
      to participate, in concert with perirhinal cortex, in
      storing memories of visual paterns.
   Amygdala
    ◦ Plays a role in memory for experiences with
      emotional significance.
    ◦ Rats with amygdalar lesions, unlike intact rats, do
      not respond with fear to a neutral stimulus that has
      been repeatedly followed y electric foot shocks.
   Prefrontal Cortex
    ◦ The area of frontal cortex anterior to motor cortex
    ◦ Are not grossly amnesic; they often display no
      deficits at all on conventional tests of memory.
    Two memory abilities that are often lost by patients
      with large prefrontal lesion
     deficit in memory for the temporal order of
      events, even when they remember the events
      themselves
     Deficits in working memory- the ability to maintain
      relevant memories while a task is being completed.
   Cerebellum
    ◦ Thought to participate in the storage of memories
      of learned sensorimotor skills through its various
      neuroplastic mechanisms


   Striatum
    ◦ Thought to store memories for consistent
      relationships between stimuli and responses- the
      type of memories that develop incremental over
      many trials.
   What is happening within the brain structures
    involved in memory?
   The efficiency of synaptic transmission were
    the basis of long-term memory- Hebb
   Long-Term Potentiation (LTP) - synapses are
    effectively made stronger by repeated
    stimulation
   Hebb hypothesized that consistent with the
    synaptic changes are the neural basis of
    learning and memory
    LTP can last for many weeks after multiple
    stimulations
   It is developed only if the firing of presynaptic
    neuron is followed by the firing of the
    postsynaptic neuron.
   Hebb’s Postulate for learning- The Co-
    occurrence is necessary for learning and
    memory
The idea that LTP is related to the neural
   mechanisms of learning and memory has
   some several observations:
(1) Elicited by levels of stimulation that mimic
    normal neural activity
(2) LTP effects greatest in brain areas involved
    in learning and memory
(3) Learning can produce LTP-like changes
(4) Drugs that impact learning often have
    parallel effects on LTP
    All of the evidence is indirect that supports a
     role of LTP in learning and Memory
    Has three part process:
1.    Induction (learning),
2.    maintenance (memory) and
3.     expression (recall)
   Usually studied at synapses at which NMDA
    receptor is prominent.
   NMDA receptor is a receptor for glutamate
    which is the main excitatory neurotransmitter
    of the brain.
   NMDA receptors do not respond maximally
    unless glutamate binds and the neuron is
    already depolarized
   Calcium channels do not open fully unless
    both conditions are met
   Learning Calcium influx only occurs if there is
    the co-occurrence that is needed for
    LTP, leading to the binding of glutamate at an
    NMDA receptor that is already depolarized
   Calcium influx may activate protein kinases
    that induces changes causing LTP
   The maintenance and expression of LTP
    involve changes in both presynaptic and
    postsynaptic neurons.
   Only those synapses that were depolarized
    before high-frequency stimulation were
    involved in LTP
   The maintenance of LTP involves structural
    changes which depend on protein synthesis
   The discovery of structural changes in
    neurons following the induction of LTP
    stimulated a search for a mechanism by
    which neuron’s activity could change its
    structure which led to the discovery of
    transcription factors.
   Nitric oxide synthesized in postsynaptic
    neurons in response to calcium influx may
    diffuse back to presynaptic neurons
    Structural changes are now a well-established
    consequence of LTP

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Final biopsyCHOLOGY REPORT

  • 2. Monkeys with bilateral medial temporal lobectomies have major problems forming long-term memories for objects encountered in the delayed nonmatching-to-sample test.
  • 3.
  • 4. Intact , well-trained monkeys performed correctly on about 90% of delayed nonmatching-to-sample trials when the retention intervals were a few minutes or less.  In contrast, monkeys with bilateral medial temporal lobe lesions had major object- recognition deficits.
  • 5. 100 80 60 Medial temporal lobe 40 lesions Normal controls 20 0 8 15 1 minute 10 seconds seconds minutes
  • 6. The development of the delayed nonmatching-to- sample test for monkeys provided a means of testing the assumptions that the amnesia resulting from medial temporal lobe damage is entirely the consequence of hippocampal damage.
  • 7. Aspiration lesions of the hippocampus in monkeys and rats. Because of differences in the size and location of the hippocampus in monkeys and in rats, hippocampectom y typically involves the removal of large amounts of rhinal cortex in monkeys, but not in rats.
  • 8. Mumby box  David Mumby  Delayed nonmatching-to-sample test for rats  It was assumed that rats could not perform a task as complex as that required for the delayed nonmatching-to-sample test. Combined bilateral lesions of rats’ hippocampus, amgdala, & rhinal cortex produce major retention deficits at all but the shortest retention intervals.
  • 9.
  • 10. Hippocampal lesions consistently disrupt the performance of tasks that involve the memory for spatial location.  Morris water maze test ◦ Rats with hippocampal lesions learn the task with great difficulty.  Radial arm maze test ◦ Intact rats readily learn to visit only those that contain food, without visiting the same arm more than once each day.
  • 11. Radial arm maze test ◦ Reference memory-memory for the general principles and skills that are required to perform a task ◦ Ability to visit only the baited arms of the radial arm maze. ◦ Working memory-temporary memory that is necessary for the successful performance of a task on which one is currently working. ◦ Ability to refrain from visiting an arm more than once in a given day ◦ Rats with hippocampal lesions display major deficits on both ref. & working memory.
  • 12. Place cells ◦ Neurons that respond only when a subject is in specific locations. ◦ By placing a rat in an ambiguous situation in a familiar test environment, it is possible to determine whether the rat thinks it is from the route that it takes to get to the location in the environment where it has previously been rewarded
  • 13. Species of birds that remember where they store seeds have larger hippocampuses than birds that do not store seeds, supporting the idea that hippocampus is important for spatial memory in many, if not all, species.
  • 14. Experiment with humans in virtual-reality towns (show activity in hippocampus using positron emission tomography, PET) and with taxi drivers (bigger hippocampuses measured with magnetic resonance imaging, MRI) also support this idea.
  • 15. Cognitive map theory ◦ O’Keefe and Nadel ◦ There are several systems in the brain that specializes in the memory for different kinds of information, and the specific function of the hippocampus is the storage of memories for spatial location.
  • 16. Brown and Aggleton Theory of the role of hippocampus in object recognition that emphasizes its relation to the perirhinal cortex. ◦ Perirheral cortex, not the hippocampus, plays a key role in most object-recognition tasks.
  • 17. Configural association memory ◦ Based on the premise that spatial memory is one specific manifestation of the hippocampus’s more general function. ◦ Hippocampus plays a role in the retention of the behavioral significance of combinations of stimuli, but not of individual stimuli.
  • 18. Inferotemporal Cortex ◦ The cortex of the inferior temporal lobe ◦ Involved in the perception of objects, it is thought to participate, in concert with perirhinal cortex, in storing memories of visual paterns.
  • 19. Amygdala ◦ Plays a role in memory for experiences with emotional significance. ◦ Rats with amygdalar lesions, unlike intact rats, do not respond with fear to a neutral stimulus that has been repeatedly followed y electric foot shocks.
  • 20. Prefrontal Cortex ◦ The area of frontal cortex anterior to motor cortex ◦ Are not grossly amnesic; they often display no deficits at all on conventional tests of memory. Two memory abilities that are often lost by patients with large prefrontal lesion  deficit in memory for the temporal order of events, even when they remember the events themselves  Deficits in working memory- the ability to maintain relevant memories while a task is being completed.
  • 21. Cerebellum ◦ Thought to participate in the storage of memories of learned sensorimotor skills through its various neuroplastic mechanisms  Striatum ◦ Thought to store memories for consistent relationships between stimuli and responses- the type of memories that develop incremental over many trials.
  • 22. What is happening within the brain structures involved in memory?  The efficiency of synaptic transmission were the basis of long-term memory- Hebb  Long-Term Potentiation (LTP) - synapses are effectively made stronger by repeated stimulation
  • 23. Hebb hypothesized that consistent with the synaptic changes are the neural basis of learning and memory  LTP can last for many weeks after multiple stimulations  It is developed only if the firing of presynaptic neuron is followed by the firing of the postsynaptic neuron.  Hebb’s Postulate for learning- The Co- occurrence is necessary for learning and memory
  • 24. The idea that LTP is related to the neural mechanisms of learning and memory has some several observations: (1) Elicited by levels of stimulation that mimic normal neural activity (2) LTP effects greatest in brain areas involved in learning and memory (3) Learning can produce LTP-like changes (4) Drugs that impact learning often have parallel effects on LTP
  • 25. All of the evidence is indirect that supports a role of LTP in learning and Memory  Has three part process: 1. Induction (learning), 2. maintenance (memory) and 3. expression (recall)
  • 26. Usually studied at synapses at which NMDA receptor is prominent.  NMDA receptor is a receptor for glutamate which is the main excitatory neurotransmitter of the brain.  NMDA receptors do not respond maximally unless glutamate binds and the neuron is already depolarized  Calcium channels do not open fully unless both conditions are met
  • 27. Learning Calcium influx only occurs if there is the co-occurrence that is needed for LTP, leading to the binding of glutamate at an NMDA receptor that is already depolarized  Calcium influx may activate protein kinases that induces changes causing LTP
  • 28. The maintenance and expression of LTP involve changes in both presynaptic and postsynaptic neurons.  Only those synapses that were depolarized before high-frequency stimulation were involved in LTP  The maintenance of LTP involves structural changes which depend on protein synthesis
  • 29. The discovery of structural changes in neurons following the induction of LTP stimulated a search for a mechanism by which neuron’s activity could change its structure which led to the discovery of transcription factors.  Nitric oxide synthesized in postsynaptic neurons in response to calcium influx may diffuse back to presynaptic neurons Structural changes are now a well-established consequence of LTP