Physiology III
Neuroscience
Exam III - Essay #5

That which is in red was updated after input from Dr. Winterson...See below

Describe the types of human memory and the brain circuitry involved. Explain the pathophysiology of Alzheimer’s disease.

Memory Types:

  1. immediate – lasts seconds
  2. short term – lasts seconds to minutes
  3. intermediate long term – lasts days to weeks
  4. long term – lasts years to lifetime

Memory is a function of synapses – occurs each time certain types of sensory signals pass thru a sequence of synapses. Facilitation occurs in that each time a certain sequence is followed it becomes easier to activate this circuit with subsequent attempts. There are several theories of how memory is laid down:

  1. Immediate memory
    1. Lasts seconds
  2. Short term memory
    1. caused by continued neural activity resulting from nerve signals that travel around in a temporary memory trace thru a circuit of reverberating neurons.
    2. Presynaptic facilitation or inhibition (the brain’s ability to ignore sensory input that is or no consequence) – occurs at synapses of presynaptic terminal and not on the neuron. The neurotransmitter (NT) causes a prolonged facilitation or inhibition lasting seconds to minutes.
    3. Synaptic potentiation – which can enhance synaptic conduction. Can result from accumulation of Ca++ ions in presynaptic terminal which can cause prolonged release of NT substance at the synapse
  3. Intermediate long term memory – via habituation (progressive closure of Ca++ channels of presynaptic terminal) or via facilitation. The following is the mechanism for facilitation and according to Guyton occurs in the sea slug Aplysia:
    1. stimulation of facilitator terminal at same time as sensory terminal causes release of serotonin.
    2. Serotonin moves to serotonin receptors in sensory terminal membrane, which activate AC in membrane, which causes formation of cAMP.
    3. CAMP activates protein kinase, which phosphorylates the protein in the K+ channels of sensory terminal membrane which blocks channels. – block can last minutes to weeks.
    4. Lack of K+ conductance causes prolonged AP in presynaptic terminal.
    5. Prolonged AP causes prolonged activation of Ca++ pores, which allows large quantities of Ca++ to enter sensory terminal, which facilitates synaptic transmission.
      Another term for this process is long term potentiation – one model suggests that there is a release of glutamate which causes the NMDA type receptor of the hippocampal cells to allow an increase in Ca++ to enter the cell. This causes a biochemical change and thus the release of nitric oxide which diffuses back across to the presynaptic terminal and acts on the terminal to permanently increase its release of glutamate. The more the circuit is activated the easier it is to activate it. Another theory of memory consolidation is that when several synapses are present on a single cell, the input from these synapse is integrated (added together). In long term potentiation, one synapse fires in a particular temporal pattern. This changes the likelihood of that synapse and other synapses activating the target cell. This may be due to an increased probability that transmitter will be released from the presynaptic cell, or an increased response in the postsynaptic cell to the same amt of NT, or both. This has been demonstrated at terminals of the perforant pathway in the dentate gyrus and at the synapses of CA3 pyramidal cells on CA1 cells (located in the hippocampus) via the NT glutamate.
      6.
  4. Long term memory – thought to result from actual structural changes not just chemical changes – a restructuring of the synapses to increase sensitivity for transmitting nervous signals
    1. increase # of vesicle release sites for secretion of transmitter substance
    2. increase # or transmitter vesicles
    3. increase # of presynaptic terminals

Circuitry:
Short to long term consolidation occurs at perforant pathway of dentate gyrus and at synapses of CA3 pyramidal cells which project to CA1 cells – these are located in the hippocampus via NT – glutamine. Short term memory is thought to also come from mammillary nuclei which project to subiculum of hippocampus. Projections come in from and go out to the cerebral cortex, thalamus, and upper reticular formation of brain stem.

Alzheimer’s disease:
Premature aging of the brain – loss of memory and cognitive function – presenile dementia. Affects more than 1 million Americans. It can only be diagnosed definitively by postmortem brain exam. It is caused by degeneration of neurons in cerebral cortex, hippocampus, and substantia innominata which is part of the globus pallidus of basal ganglia. The acetylcholine containing cells are lost and the activity of choline acetyltransferase in the cortex and hippocampus is extremely low. There are an accumulation of neurofibrillary tangles and neuritic or amyloid plaques in the cortex, hippocampus, basal ganglia, thalamus, and cerebellum. Damage or the abnormalities are usually seen 1st in the subiculum and entorhinal cortices thus relay of info through the hippocampus is impeded which causes the memory deficits.
The comments in this box are from Dr. Winterson.  They have been integrated into the essay outline above and highlighted in red.
"My main suggestion is to replace your discussion of intermediate memory (which currently describes mechanisms in Aplysia (sea slug)) with the discussion found on page 450 of Haines under long-term potentiation. Not only does this describe mechanisms that have been studied in depth in the hippocampus but it is likely that a mechanism with these features are responsible for the structural changes mentioned to explain long-term memory."

Last Updated 09/06/01 08:53:37 PM
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