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Balanced cortical microcircuitry for maintaining information in working memory

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Abstract

Persistent neural activity in the absence of a stimulus has been identified as a neural correlate of working memory, but how such activity is maintained by neocortical circuits remains unknown. We used a computational approach to show that the inhibitory and excitatory microcircuitry of neocortical memory-storing regions is sufficient to implement a corrective feedback mechanism that enables persistent activity to be maintained stably for prolonged durations. When recurrent excitatory and inhibitory inputs to memory neurons were balanced in strength and offset in time, drifts in activity triggered a corrective signal that counteracted memory decay. Circuits containing this mechanism temporally integrated their inputs, generated the irregular neural firing observed during persistent activity and were robust against common perturbations that severely disrupted previous models of short-term memory storage. These results reveal a mechanism for the accumulation and storage of memories in neocortical circuits based on principles of corrective negative feedback that are widely used in engineering applications.

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Figure 1: Memory networks with negative-derivative feedback.
Figure 2: Negative derivative–feedback networks of excitatory and inhibitory populations.
Figure 3: Negative-derivative feedback with mixture of NMDA and AMPA synapses in all excitatory pathways.
Figure 4: Robustness to common perturbations in memory networks with derivative feedback.
Figure 5: Irregular firing in spiking networks with graded persistent activity.
Figure 6: Synaptic inputs in derivative-feedback and common positive-feedback models.

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Acknowledgements

We thank D. Fisher for valuable discussions and E. Aksay, K. Britten, N. Brunel, D. Butts, J. Ditterich, R. Froemke, A. Goddard, D. Kastner, B. Lankow, S. Luck, B. Mulloney, J. Raymond, J. Rinzel and M. Usrey for valuable discussions and feedback on the manuscript. We thank A. Lerchner for providing code for our initial simulations of spiking network models. This research was supported by US National Institutes of Health grants R01 MH069726 and R01 MH065034, a Sloan Foundation fellowship, and a University of California Davis Ophthalmology Research to Prevent Blindness grant.

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S.L. and M.S.G. designed the study, analyzed the data and wrote the manuscript.

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Correspondence to Mark S Goldman.

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Lim, S., Goldman, M. Balanced cortical microcircuitry for maintaining information in working memory. Nat Neurosci 16, 1306–1314 (2013). https://doi.org/10.1038/nn.3492

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