UC San Diego

In mammals, the consolidation of memories from previous waking is facilitated through the coordination of hippocampo-cortical waves during non-rapid eye movement sleep (NREM). Specifically, it is thought that consolidation in the cortex is guided by the coordination of cortical sleep waves (downstates, spindles, upstates) with high-frequency oscillations in the hippocampus called ‘ripples,’ which in rodents mark the replay of neuronal firing sequences established during waking. However, it is not well-understood how these waves facilitate plasticity. While it has been shown that cortical ripples are involved in memory recall in humans, it is not known whether they are generated during human sleep. Furthermore, it remains unknown how the different elements of a memory are bound across the cortex into a cohesive representation. In this dissertation, I collected and analyzed human intracranial macro- and micro-electrode recordings to investigate how interactions between cortical waves, hippocampal waves, and single unit spiking may underlie memory during sleep and waking. Chapter 1 shows how sleep spindles modulate neuron spike-timing to create conditions necessary for spike-timing-dependent plasticity (STDP). This study reveals that spindles facilitate short latency co-firing between neurons that may lead to STDP. Furthermore, it reports the spatial organization and propagation of spindles and spiking within a few millimeters of cortex. Chapter 2 provides the first report and comprehensive characterization of 80 Hz cortical ripples during human NREM, and provides evidence for their role in memory consolidation. This study shows that ripples are ubiquitous throughout the cortex during NREM as well as waking. During sleep, cortical ripples occur during spindles on down-to-upstates, with unit-firing patterns suggesting generation by pyramidal-interneuron feedback. Furthermore, cortical ripples mark the recurrence of spatiotemporal activity patterns from preceding waking and group co-firing, which could further enhance spindle-mediated STDP. Chapter 3 reveals that ripples occur simultaneously in multiple lobes in both hemispheres, and in the hippocampus, generally during sleep and waking, and with enhancements preceding memory recall. Ripples phase-lock local cell-firing, and phase-synchronize with little decay between locations separated by up to 25 cm, enabling long distance integration. Indeed, co-rippling sites have increased correlation of very-high-frequency activity which reflects cell-firing. Thus, ripples may help bind information across the cortex in memory.