Rathat: A self-targeting printable brain implant system

There has not been a major change in how neuroscientists approach stereotaxic methods in decades. Here, we present a new stereotaxic method that provides an alternative approach to a traditional u-frame stereotaxic device and reduces costs, surgical time, and aids repeatability. The RatHat brain implantation system is a 3Dprintable stereotaxic device for rats that is fabricated prior to surgery and fits to the shape of the skull. RatHat builds are directly implanted into the brain without the need for head-leveling or coordinate-mapping during surgery. The RatHat can be used in conjunction with the traditional u-frame stereotaxic device, but does not require the use of a micromanipulator for successful implantations. Each RatHat contains several primary components including the implant for mounting intracranial components, the surgical stencil for targeting drill sites, and the protective cap for preventing damage from impacts and debris. Each component serves a unique function and can be used together or separately. We demonstrate the feasibility of the RatHat in four different proof-of-principle experiments: (1) a three-pole cannula apparatus, (2) an optrode-electrode assembly, (3) a fixed-electrode array, and (4) a tetrode hyperdrive. Implants were successful, durable, and long-lasting (up to nine months). RatHat print files are easily created, can be modified in computer aided design (CAD) software for a variety of applications, and are easily shared, contributing to open science goals and replications. The RatHat has been adapted to multiple experimental paradigms in our lab and should be a useful new way to conduct stereotaxic implant surgeries in rodents

Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events

We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC→RE and mPFC→PER projections regulate sequence memory retrieval. First, we found non-overlapping populations of mPFC cells project to RE and PER. Second, suppressing mPFC activity impaired sequence memory. Third, inhibiting mPFC→RE and mPFC→PER pathways effectively abolished sequence memory. Finally, a sequential lag analysis showed that the mPFC→RE pathway contributes to a working memory retrieval strategy, whereas the mPFC→PER pathway supports a temporal context memory retrieval strategy. These findings demonstrate that mPFC→RE and mPFC→PER pathways serve as top-down mechanisms that control distinct sequence memory retrieval strategies

Awake delta and theta-rhythmic hippocampal network modes during intermittent locomotor behaviors in the rat.

Delta-frequency network activity is commonly associated with sleep or behavioral disengagement accompanied by a dearth of cortical spiking, but delta in awake behaving animals is not well understood. We show that hippocampal (HC) synchronization in the delta frequency band (1–4 Hz) is related to animals’ locomotor behavior using detailed analyses of the HC local field potential (LFP) and simultaneous head- and body-tracking data. In contrast to running-speed modulation of the theta rhythm (6–10 Hz), delta was most prominent when animals were stationary or moving slowly, that is, when theta and fast gamma (65–120 Hz) were weak, and often developed rapidly when animals paused briefly between runs. We next combined time-frequency decomposition of the LFP with hierarchical clustering algorithms to categorize momentary estimations of the power spectral density (PSD) into putative modes of HC activity. Delta and theta power were strikingly orthogonal across spectral modes, as well as across bouts of precisely defined running and stationary behavior. Delta-band and theta-band coherences between HC recording sites were monotonically related to theta-delta ratios across modes; and whereas theta coherence between HC and medial prefrontal cortex (mPFC) increased during running, delta-band coherence between mPFC and HC increased during stationary bouts. Taken together, our findings suggest that delta-dominated network modes (and corresponding mPFC-HC couplings) represent functionally distinct circuit dynamics that are temporally and behaviorally interspersed among theta-dominated modes during navigation. As such, delta modes could play a fundamental role in coordinating encoding and retrieval mechanisms or decision-making processes at a timescale that segments event sequences within behavioral episodes. (PsycInfo Database Record (c) 2021 APA, all rights reserved

Nucleus reuniens transiently synchronizes memory networks at beta frequencies

Abstract Episodic memory-based decision-making requires top-down medial prefrontal cortex and hippocampal interactions. This integrated prefrontal-hippocampal memory state is thought to be organized by synchronized network oscillations and mediated by connectivity with the thalamic nucleus reuniens (RE). Whether and how the RE synchronizes prefrontal-hippocampal networks in memory, however, remains unknown. Here, we recorded local field potentials from the prefrontal-RE-hippocampal network while rats engaged in a nonspatial sequence memory task, thereby isolating memory-related activity from running-related oscillations. We found that synchronous prefrontal-hippocampal beta bursts (15–30 Hz) dominated during memory trials, whereas synchronous theta activity (6–12 Hz) dominated during non-memory–related running. Moreover, RE beta activity appeared first, followed by prefrontal and hippocampal synchronized beta, suggesting that prefrontal-hippocampal beta could be driven by the RE. To test whether the RE is capable of driving prefrontal-hippocampal beta synchrony, we used an optogenetic approach (retroAAV-ChR2). RE activation induced prefrontal-hippocampal beta coherence and reduced theta coherence, matching the observed memory-driven network state in the sequence task. These findings are the first to demonstrate that the RE contributes to memory by driving transient synchronized beta in the prefrontal-hippocampal system, thereby facilitating interactions that underlie memory-based decision-making