The strikingly linear relationship between response probability and response time is likely
a fundamental property of our short term memory. The tagging model is a compelling explanation
of the data. But any memory process is one of biochemistry. What could possibly be a
biochemical mechanism explaining the tagging model? We know that long term memory is
related to long term synaptic changes presumably via protein synthesis (6). Short term behavior
in aplysia can also be related to changes in the synapses: “serotonin leads to an increase in
presynaptic cAMP, which activates PKA and leads to synaptic strengthening through enhanced
transmitter release produced by a combination of mechanisms”(6). Thus it is tempting to search
for something that quickly tags synapses and more slowly untags them and does so in a
reversible fashion (if the changes are not reversible, it would be long term memory rather than
short term). Such a system is the cycle of exocytosis and endocytosis of neurotransmitter
vesicles in the presynaptic terminal.
3. The Cycle of Exocytosis and Endocytosis
Neurotransmitter is stored in small vesicles in the presynaptic terminal (for an introduction
please see (7) pp. 105-7 and the introduction in (8)) and on can surmise that “all presynaptic
functions, directly or indirectly, involve synaptic vesicles” (9) (exocytosis and endocytosis has
been reviewed elsewhere ((9) and (10)).
When an action potential occurs in the presynaptic neuron, the Ca2+ channels open and
in 10-20% of cases (11),(12) cause one (12) vesicle to fuse to the plasma membrane of the
presynaptic terminal and open up a pore into the synaptic cleft and release neurotransmitter into
the synaptic cleft (exocytosis). After repeated stimulation available vesicles in what is called the
Readily Releasable Pool of vesicles (RRP, for reviews of the RRP see (13) and (9)) can be
completely depleted. Exocytosis results in neurotransmitters crossing over to the receptors in the
postsynaptic terminal and they are quickly broken down by enzymes in the synaptic cleft.
Exocytosis is a possible candidate for the tagging process. In Figure 10 is shown the
average time course for exocytosis (depletion of the Readily Releasable Pool (RRP) of
neurotransmitter vesicles) in a rat hippocampal culture (12). It is quasi-linear and the overall time
is a little over 1 second, consistent with the tagging time in the experiments quoted (calculated in
(1) to range from 0.2 to 1.8 seconds). Full tagging corresponds to a state of the synapse in which
the presynaptic neurons are no longer actively influencing the postsynaptic neuron, in effect,
limiting the size of the overall neural excitation corresponding to the recalled or recognized word.