CNS*2026 Halifax

Introduction
Working memory and decision making are mediated by common cortical areas [1], but they make conflicting demands of circuit dynamics. Competition between neural populations is essential for decision making, but exacerbates working memory storage limitations. This discrepancy implies a mechanism for mediating between dynamic regimes. VIPs are strong candidates for this role, as they receive long-range cortical and modulatory inputs, and selectively target classes of inhibitory interneurons with varying connectivity profiles [2,3]. As such, VIPs are well positioned to integrate a range of task factors and to control the spatial structure of inhibition in a context-dependent manner, providing a rich mechanism for cognitive flexibility.

Methods
We developed a cortical circuit model comprising pyramidal neurons, large basket cells (broad, indiscriminate inhibition) and small basket cells (local surround inhibition) [4], connected by AMPA, NMDA, and GABA receptor synapses with conductance strengths informed by electrophysiological data. VIP control was simulated by independently modulating inhibitory conductance onto each interneuron class. We simulated a luminance-contrast visual discrimination task in which the network identified a target among distractors and a visuospatial working memory task in which the network maintained stimulus information across a delay. Both tasks received identical stimuli to enable direct comparison between the dynamics imposed by inhibitory structure.

Results
Under a single set of parameter values, our model accounts for neural and behavioural signatures of decision making and working memory. On our decision task, these data include target-selective and distractor-selective neural activity, and psychometric and chronometric curves. On our working memory task, they include statistics of persistent mnemonic activity and storage limitations. Local inhibition has a strong stabilizing effect in the model, attenuating the competitive dynamics engendered by large basket cells. As such, VIPs establish a decision regime by preferentially targeting small basket cells (local disinhibition) and establish a working memory regime by targeting large basket cells (broad disinhibition).

Discussion
Our findings support the hypothesis that VIPs mediate flexible cognitive control by selectively targeting inhibitory cell classes with different connectivity profiles, effectively determining the spatial structure of inhibition in cortical circuits. This mechanism enables the rapid switching between task-appropriate dynamic regimes for decision making (competition) and working memory (stability with minimal competition) as well as fine-tuning the dynamics within each regime. The model makes testable predictions for neural and behavioural data from visual discrimination and working memory tasks.

References

1. Murray, J. D., Jaramillo, J., & Wang, X. J. (2017). Working memory and decision-making in a frontoparietal circuit model. Journal of Neuroscience, 37(50), 12167-12186.
2. Pi, H. J., Hangya, B., Kvitsiani, D., Sanders, J. I., Huang, Z. J., & Kepecs, A. (2013). Cortical interneurons that specialize in disinhibitory control. Nature, 503(7477), 521-524.
3. Wall, N. R., De La Parra, M., Sorokin, J. M., Taniguchi, H., Huang, Z. J., & Callaway, E. M. (2016). Brain-wide maps of synaptic input to cortical interneurons. Journal of Neuroscience, 36(14), 4000-4009.
4. Wang, Y., Gupta, A., Toledo-Rodriguez, M., Wu, C. Z., & Markram, H. (2002). Anatomical, physiological, molecular and circuit properties of nest basket cells in the developing somatosensory cortex. Cerebral cortex, 12(4), 395-410.