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Total recall: episodic memory retrieval,choice, and memory confidence in the rat

Video Abstract (AI generated) Paper Preprint Supplementary Information

Episodic memory enables recollection of past experiences to guide future behavior. Humans know which memories to trust (high confidence) and which to doubt (low confidence). How memory retrieval, memory confidence, and memory-guided decisions are related, however, is not understood. Additionally, whether animals can assess confidence in episodic memories to guide behavior is unknown. We developed a spatial episodic memory task in which rats were incentivized to gamble their time: betting more following a correct choice yielded greater reward. Rat behavior reflected memory confidence, with higher temporal bets following correct choices. We applied modern machine learning to identify a memory decision variable, and built a generative model of memories evolving over time that accurately predicted both choices and confidence reports. Our results reveal in rats an ability thought to exist exclusively in primates, and introduce a unified model of memory dynamics, retrieval, choice, and confidence.

Constant sub-second cycling between representations of possible futures in the hippocampus

Cell, 2020-01-30

Video Abstract (AI generated) Paper Preprint Cell

Cognitive faculties such as imagination, planning, and decision-making entail the ability to project into the future. Crucially, animal behavior in natural settings implies that the brain can generate representations of future scenarios not only quickly but also constantly over time, as external events continually unfold. Despite this insight, how the brain accomplishes this remains unknown. Here we report neural activity in the hippocampus encoding two future scenarios (two upcoming maze paths) in constant alternation at 8 Hz: one scenario per 8 Hz cycle (125 ms). We further found that the underlying cycling dynamic generalized across multiple hippocampal representations (location and direction) relevant to future behavior. These findings identify an extremely fast and regular dynamical process capable of representing future possibilities.

High-density, long-lasting, and multi-region electrophysiological recordings using polymer electrode arrays

Neuron, 2018-11-27

Video Abstract (AI generated) Paper Preprint Neuron

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to months. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track 25% of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.

A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain

Journal of Neural Engineering, 2019-06-19

Video Abstract (AI generated) Paper Preprint Journal of Neural Engineering

Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip. We describe a novel design and fabrication process to create silicon insertion shuttles that are sharp in three dimensions and can penetrate rat dura, for faster, easier, and less damaging implantation of polymer arrays. Sharpened profiles are obtained by reflowing patterned photoresist, then transferring its sloped profile to silicon with dry etches. We demonstrate that sharpened shuttles can reliably implant polymer probes through dura to yield high quality single unit and local field potential recordings for at least 95 days. On insertion directly through dura, tissue compression is minimal. This is the first demonstration of a rat dural-penetrating array for chronic recording. This device obviates the need for a durotomy, reducing surgical time and risk of damage to the blood-brain barrier. This is an improvement to state-of-the-art flexible polymer electrode arrays that facilitates their implantation, particularly in multi-site recording experiments. This sharpening process can also be integrated into silicon electrode array fabrication.

Hippocampal replay of experience at real-world speeds

Video Abstract (AI generated) Paper Preprint Supplemental Movie 3 Supplemental Movie 2 Supplemental Movie 1 (github,"") (github,"")

Representations of past and possible future experiences play a critical role in memory and decision-making processes. The hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain "replay" of spatial trajectories at ~20x real-world speeds. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here we develop a state space model that uses a combination of movement dynamics of different speeds to capture the spatial content and time evolution of replay during SWRs. Using this model, we find that the large majority of replay events contain spatially coherent, interpretable content. Furthermore, most events progress at real-world, rather than accelerated, movement speeds, consistent with actual experiences. ### Competing Interest Statement The authors have declared no competing interest.