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The Journal of Neuroscience, January 1, 2000, 20(1):485-494
Destruction and Creation of Spatial Tuning by Disinhibition:
GABAA Blockade of Prefrontal Cortical Neurons Engaged
by Working Memory
Srinivas G.
Rao,
Graham V.
Williams, and
Patricia S.
Goldman-Rakic
Section of Neurobiology, Yale University School of Medicine, New
Haven, Connecticut 06510
Local circuit neurons in the dorsolateral prefrontal cortex (dPFC)
of monkeys have been implicated in the cellular basis of working
memory. To further elucidate the role of inhibition in spatial tuning,
we iontophoresed bicuculline methiodide (BMI) onto functionally
characterized neurons in the dPFC of monkeys performing an oculomotor
delayed response task. This GABAA blockade revealed that
both putative interneurons and pyramidal cells possess significant
inhibitory tone in the awake, behaving monkey. In addition, BMI
application primarily resulted in the loss of previously extant spatial
tuning in both cell types through reduction of both isodirectional and
cross-directional inhibition. This tuning loss occurred in both the
sensorimotor and mnemonic phases of the task, although the delay
activity of prefrontal neurons appeared to be particularly affected.
Finally, application of BMI also created significant spatial tuning in
a sizable minority of units that were untuned in the control condition.
Visual field analysis of such tuning suggests that it is likely caused
by the unmasking of normally suppressed spatially tuned excitatory
input. These findings provide the first direct evidence of directional
inhibitory modulation of pyramidal cell and interneuron firing in both
the mnemonic and sensorimotor phases of the working memory process, and
they implicate a further role for GABAergic interneurons in the
construction of spatial tuning in prefrontal cortex.
Key words:
primate; inhibition; prefrontal cortex; interneurons; spatial tuning; bicuculline; working memory; fast spiking
Copyright © 2000 Society for Neuroscience 0270-6474/0/201485-10$05.00/0
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