Working memory (WM) is a key component of human memory and cognition. Computational models have been used to study the underlying neural mechanisms, but neglected the important role of short-term memory (STM) and long-term memory (LTM) interactions for WM. Here, we investigate these using a novel multiarea spiking neural network model of prefrontal cortex (PFC) and two parietotemporal cortical areas based on macaque data. We propose a WM indexing theory that explains how PFC could associate, maintain, and update multimodal LTM representations. Our simulations demonstrate how simultaneous, brief multimodal memory cues could build a temporary joint memory representation as an “index” in PFC by means of fast Hebbian synaptic plasticity. This index can then reactivate spontaneously and thereby also the associated LTM representations. Cueing one LTM item rapidly pattern completes the associated uncued item via PFC. The PFC–STM network updates flexibly as new stimuli arrive, thereby gradually overwriting older representations.

We present an electrophysiological model of double bouquet cells and integrate them into an established cortical columnar microcircuit model that has previously been used as a spiking attractor model for memory. Learning in that model relies on a Hebbian-Bayesian learning rule to condition recurrent connectivity between pyramidal cells. We here demonstrate that the inclusion of a biophysically plausible double bouquet cell model can solve earlier concerns about learning rules that simultaneously learn excitation and inhibition and might thus violate Dale’s principle. We show that learning ability and resulting effective connectivity between functional columns of previous network models is preserved when pyramidal synapses onto double bouquet cells are plastic under the same Hebbian-Bayesian learning rule. The proposed architecture draws on experimental evidence on double bouquet cells and effectively solves the problem of duplexed learning of inhibition and excitation by replacing recurrent inhibition between pyramidal cells in functional columns of different stimulus selectivity with a plastic disynaptic pathway. We thus show that the resulting change to the microcircuit architecture improves the model’s biological plausibility without otherwise impacting the model’s spiking activity, basic operation, and learning abilities.