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The Journal of Neuroscience, November 1, 1999, 19(21):9587-9603
Synaptic Basis of Cortical Persistent Activity: the Importance of
NMDA Receptors to Working Memory
Xiao-Jing
Wang
Volen Center for Complex Systems and Department of Physics,
Brandeis University, Waltham, Massachusetts 02454-9110
Delay-period activity of prefrontal cortical cells, the neural
hallmark of working memory, is generally assumed to be sustained by
reverberating synaptic excitation in the prefrontal cortical circuit.
Previous model studies of working memory emphasized the high efficacy
of recurrent synapses, but did not investigate the role of temporal
synaptic dynamics. In this theoretical work, I show that biophysical
properties of cortical synaptic transmission are important to the
generation and stabilization of a network persistent state. This is
especially the case when negative feedback mechanisms (such as
spike-frequency adaptation, feedback shunting inhibition, and
short-term depression of recurrent excitatory synapses) are included so
that the neural firing rates are controlled within a physiological
range (10-50 Hz), in spite of the exuberant recurrent excitation.
Moreover, it is found that, to achieve a stable persistent state,
recurrent excitatory synapses must be dominated by a slow component. If
neuronal firings are asynchronous, the synaptic decay time constant
needs to be comparable to that of the negative feedback; whereas in the
case of partially synchronous dynamics, it needs to be comparable to a
typical interspike interval (or oscillation period). Slow synaptic
current kinetics also leads to the saturation of synaptic drive at high
firing frequencies that contributes to rate control in a persistent
state. For these reasons the slow NMDA receptor-mediated synaptic
transmission is likely required for sustaining persistent network
activity at low firing rates. This result suggests a critical role of
the NMDA receptor channels in normal working memory function of the prefrontal cortex.
Key words:
working memory; prefrontal cortex; persistent activity; NMDA receptor; synaptic dynamics; short-term plasticity; rate control; synchronization; spiking neuron model
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219587-17$05.00/0
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