Historical Perspectives, Part 3, Anatomical and neurochemical correlates of neuronal plasticity

  1. Introduction of the research questions
    1. Two primary goals of learning and memory studies are
      1. to identify the kinds of neural centers involved in specific behaviours
      2. to identify the kinds of changes that underly the observed plasticity
    2. The changes in neural functions (neuronal plasticity) might involve
      1. chemistry (the number of transmitter chemicals released),
      2. morphology (the number or types of connections made between nerve cells)
      3. electrical activity (how rapidly, or in what sequence, nerve cells fire)
  2. Changes in synapses may be mechanisms of memory storage
    1. The concept of separate nerve cells communicating through synapses (this theory is referred to as the neuron doctrine) was only slowly accepted during the 1st half of this century.
      1. Determining one nerve cell ended and another begin was difficult due to the close proximity of one with another
      2. the term synapse was first proposed by Sherrington (1906).
    2. Speculations of the changes in neuronal junction could be a mechanism to store memories (1890s)
      1. Tanzi (1893) proposed the hypothesis that the plastic changes involved in learning probably take place at the neuronal junctions
      2. Ramón y Cajal (1894) suggested that neurons extend their axons and dentrites to make new connections with other neurons in both development and learning. He further stated that the higher one looked in the vertebrate scale, the more the neural terminals and collaterals ramified.
      3. Charles Sherrington (1897) stated the synapses was likely to be strategic for learning.
  3. Donald O. Hebb (1949) suggested conditions that might be required to produce changes at synapses that could account for the development of the nervous system and for learning
      1. He proposed that functional relationship between a presynatic neuron (A) and a postsynaptic neuron (B) could change if A frequently took part in exciting B.
        1. when an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficacy, as one of the cells firing B, is increased.
      2. Extension of the hypothesis:
        1. any two cells that are repeated active at the same time will tend to become 'associated', so that activity in one facilitates activity in the other.
      3. Summary: "Neurons that fire together wire together"
      4. Synapses that show such properties are called Hebbian synapses.
  4. Two early experimental findings demonstrating the brain can be altered measurably by training and differential experience (early 1960s).
    1. Rosenzweig's group: both formal training and informal training in varied environments led to measurable changes in neurochemistry and neuroanatomy of rodent brain.
    2. Hubel and Wiesel: occluding one eye of a kitten led to reduction in the number of cortical cells responding to that eye. Critical period.
  5. Findings by Rosenzweig and associates
    1. Formal training
      1. Rats trained and tested for spatial problem task
      2. Measured AchE activity in the cerebral cortex
      3. Found the groups that had been trained and tested on more difficult problems > those given easier problems > groups given no training and testing.
    2. Informal learning, enriched experience, see Fig. 1-5
      1. increased acetylcholinesterase (AchE)
      2. increased weights of regions of neocortex.
    3. Further systematic testing
      1. Enriched condition (EC), Standard condition (SC), Isolated condition (IC)
      2. training and differential experience could produce measurable changes in the brain
      3. Changes can be produced throughout life span and rather rapidly
      4. Change were not uniformly distributed throughout cortex, largest change in occipital cortex, see Fig. 1-6
      5. Other measures, see Fig. 1-7, 1-8, 1-9, 1-10
        1. cortical thickness,
        2. sizes of neuronal cell bodies,
        3. count of dendritic spines
        4. size of the synaptic contact areas,
        5. increase in extent and branching of dendrites
        6. number of synapses per neuron
        7. increase in cortical volume and intracortical connections
        8. better learning and problem solving
  6. Neurochemical mechanisms: Protein synthesis is required for memory storage
    1. Early findings: enriched experience causes
      1. increased rate of protein synthesis
      2. Increased amounts of protein and RNA in the cortex
    2. Test of protein-synthesis hypothesis
      1. Flexner and associates: use of inhibitor of protein synthesis
      2. protein synthesis during and soon after training is necessary for formation of LTM, but STM and ITM do not require protein synthesis
  7. A false step - the ill-fated "transfer" experiments of 1960s and 1970s
      1. The idea that RNA or protein molecules could be biological code for storing individual memories
      2. If memory storage was predominantly chemical in nature, perhaps memory could be "transferred" from a trained animal to naive one by simple chemical injections.
      3. Results of the transfer experiment that could not be replicated.