Neural Connections and Memories

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Neural Connections and Memories

• Some theories of how information gets stored in
  the Brain

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1 The Organization of Memory

• Memories are not stored in single neurons
  neural links
• Memories are stored in many different locations
  in the brain
• Memories are reconstructed each time we recall
  them from a number of different brain areas
  including sensory and verbal areas. There is no
  central depository area
• D Schacters word confusion experiment using MRI
• True words cake sugar candy
• False word sweet
• True memory has inputs from auditory sections of
  the brain,
• False only from left medial temporal lobe (also
  for true words)

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2 Convergence Zones

• Antonio Damasio (Descartes' Error) proposes
• The elements of a memory come together at
  convergence zones near the sensory neurons that
  first registered the event
• Convergence zones help us conceive of objects by
  facilitating connections between the many
  features of the object
• There is a hierarchy of convergence zones
• The lower convergence zones help us understand
  specific concepts (e.g., faces in general)
• The higher ones help us to understand specific
  instances of a concept (e.g., Person As face in
  particular)
• Linking the two are intermediate convergence
  zones that allow us to identify specific features
  that distinguish a face

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3 The Hippocampus as Regulator

• The Hippocampus does not store memories
• It seems to be an intelligent collating
  machine. It filters new associations, and
  decides what to store, sorts the results, and
  sends packets of information to other parts of
  the brain
• Stored memories can be put back together without
  the hippocampus, but it is difficult to form new
  memories without it
• The intact hippocampus may also put the pieces
  of a memory stored elsewhere in the cortex
  together when we recall something

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4 Non-Sensory memories

• What about non-sensory memories such as
  reflections, beliefs, emotions?
• One suggestion is that the brain forms maps of
  its own activities
• The maps categorize, discriminate, and recombine
  the various brain activities needed to form the
  ideas and emotions
• The bits and pieces are different, but they are
  dispersed and pulled together in the same way as
  other memories

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5 The Importance of Sleep

• Electrodes planted in Hippocampi of Rats
• Recordings of cells firing in rats hippocampi
  during their exploration of a new environment
  were made
• When the re-caged rats slept the very same cells
  fired again
• Avi Karni Dov Sagi in Israel found that
• Interrupting REM sleep 60 times a night
  completely blocked learning
• This suggests that REM sleep helps organize
  pieces of memory in different parts of cortex and
  the associations between them to facilitate later
  recall and lasting memory formation

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6 Memory as stronger connections

• Donald Hebb (1949) suggested that when the axon
  of a neuron A repeatedly stimulated neuron B to
  fire, the connection between the axon and neuron
  B would be facilitated (become more effective)
• The formation of such Hebbian connections has
  been studied mainly in invertebrates such as
  Aplysia (a sea-living relative of the slug)
  because
• Nervous system is simple
• Neurons are large (as much as 1mm in diameter)

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7 Habituation in Aplysia

• Habituation decrease in response to repeatedly
  presented stimulus
• Aplysias withdrawal of gills response to
  stimulation habituates with repeated stimulation
• Not due to muscle fatigue (direct stimulation of
  muscle)
• Sensory neuron also still fires at same rate
• Thus must be the result of a change in the
  synapse between the sensory neuron and the motor
  neuron (I.e., decreased release of
  neurotransmitter)

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8 Sensitization in Aplysia

• Sensitization increase in response to mild
  stimuli as a result of previous exposure to more
  intense stimuli
• Strong stimulation excites a facilitating
  interneuron which has axons that release
  serotonin onto the presynaptic terminals of
  sensory neurons
• This closes potassium channels, which permit the
  flow of potassium out of the neuron after action
  potential and thus restore polarization
• Blocked potassium channels cause prolonged action
  potential in the presynaptic cell, additional
  transmitter release, long-term sensitization of
  the sensory neuron

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9 Long-term Potentiation in Mammals

• Learning probably causes a long-term change in
  the synapses best candidate at present
  Long-term potentiation (LTP)
• Learning memory exist in circular relationship
• Learning enables information to cross from
  perception to memory
• Stored memories affect future learning
• LTP, first identified in hippocampus, may be the
  appropriate mechanism by which this happens
• LTP occurs if one or more axons connected to a
  dendrite bombard it with brief but rapid series
  of stimuli This burst leaves the synapses
  potentiated (more responsive to same stimuli type)

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10 Properties of LTP

• Specificity if some synapses onto a cell have
  been highly active and not others, only the
  active ones are strengthened
• Cooperativity LTP tends to be produced by the
  simultaneous stimulation from two or more axons
• Associativity pairing a weak input with a
  strong input enhances the later response to the
  weak input
• LTP has an opposite pair long-term depression
  (LTD) a prolonged decrease in response to a
  synaptic input that has been repeatedly paired
  with another low-frequency input

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11 Glutamate Synapses

• Different kinds of synapses
• Dopamine, types distinguished as D1, D2
• GABA, types distinguished by letter - GABAA
• Glutamate has two types of interest AMPA and
  NMDA
• Both Glutamate synapses are ionotropic they open
  a channel when stimulated by glutamate to let one
  or more ions enter the postsynaptic cell
• AMPA opens sodium channels NMDA responds to
  glutamate only when the membrane has been partly
  depolarized, and allow entry of calcium
• All known LTP depends on glutamate synapses
• Glutamate most abundant transmitter in brain

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12 Glutamate Synapses and LTP

• Process
• Two axons repeated stimulate a dendrite
• Many sodium ions then enter through AMPA
  channels. The dendrite thus becomes (at least
  partly) depolarized
• Partly depolarized dendrite then opens NMDA
  channel
• Both sodium and calcium now enter through NMDA
  channel

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13 The importance of Calcium

• The entry of calcium through NMDA channel
• Activates many chemicals in dendrite
• Activates some otherwise inactive genes. This
  causes
• The structure of the AMPA receptor changes,
  becoming more responsive to glutamate
• Some NMDA receptors change into AMPA receptors
  (which respond more strongly to glutamate)
• The dendrite may build more AMPA receptors
• The dendrite may make more branches, forming
  additional synapses to the same axon
• Net result An increase in the responsiveness of
  the receptors to glutamate

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14 Summary of LTP Process

• Massive glutamate stimulation of AMPA receptors
  results in depolarization
• Depolarization enables glutamate to stimulate
  NMDA receptors
• This allows the entry of calcium into receptor
• The entry of calcium produces changes that
  potentiate the dendrites future response to
  glutamate
• Once LTP is established it no longer needs NMDA
  receptors to maintain potentiation I.e.,
  long-term change

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15 LTP and behaviour

• LTP a mechanism for learning (but there may be
  other mechanisms)
• LTP a process by which brain plasticity is
  achieved but there are other processes too
• As learning happens LTP takes place in
  hippocampus. 1.5 to 3 hours later we can detect
  LTP taking place in other parts of cortex (Thus
  hippocampus is perhaps a temporary store and
  transfer facility?)
• Abnormalities in NMDA receptors impair learning,
  and more of them better memory in mice

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16 LTP and Behaviour 2

• Drugs that interfere with LTP impair learning
  drugs that enhance LTP enhance learning
• Drugs may act by affecting calcium
• In old age calcium channels become leaky thus
  too much calcium within neurons. (LTP requires
  abundant calcium flow at the right time)
• Thus drugs that block calcium channels enhance
  memory in aged mammals