Dynamical Mechanisms for Coordinating Long-term Working Memory Based on the Precision of Spike-timing in Cortical Neurons

In the last century, most sensorimotor studies of cortical neurons relied on average firing rates. Rate coding is efficient for fast sensorimotor processing that occurs within a few seconds. Much less is known about long-term working memory with a time scale of hours (Ericsson and Kintsch, 1995). The discovery of the millisecond precision of spike initiation in cortical neurons was unexpected (Mainen and Sejnowski, 1995). Even more striking was the precision of spiking in vivo, in response to rapidly fluctuating sensory inputs, suggesting that neural circuits could, in principle, preserve and manipulate sensory information through spike timing. It could support spike-timing-dependent plasticity (STDP), which is triggered by the relative timing of spikes between presynaptic and postsynaptic neurons in the millisecond range. What spike-timing mechanisms could regulate STDP in vivo? Cortical traveling waves have been observed across many frequency bands with high temporal precision. Traveling waves have wave fronts that could link spike timing to STDP. As a wave front passes through a cortical column, excitatory synapses on the dendrites of both pyramidal and basket cells are synchronously stimulated. Inhibitory basket cells form a calyx on pyramidal cell bodies, and inhibitory rebound following a strong transient hyperpolarization can trigger a backpropagating action potential, which arrives shortly after the excitatory inputs on pyramidal dendrites. STDP activated in this way could persist for hours, creating a second-tier network. This temporary network could support long-term working memory, a cognitive network riding above the long-term sensorimotor network. On their own, traveling waves and STDP have not yet yielded new insights into cortical function. Together, they could be responsible for how we think (Sejnowski, 2025).