Optogenetic activation of the ventral tegmental area-hippocampal pathway facilitates rapid adaptation to changes in spatial goals.

Animal adaptation to environmental goals to pursue rewards is modulated by dopamine. However, the role of dopamine in the hippocampus, involved in spatial navigation, remains unclear. Here, we studied dopaminergic inputs from the ventral tegmental area (VTA) to the hippocampus, focusing on spatial goal persistence and adaptation. Mice with VTA dopaminergic lesions struggled to locate and update learned reward locations in a circular maze with dynamic reward locations, emphasizing the importance of VTA dopaminergic neurons in the persistence and adaptation of spatial memory. Further, these deficits were accompanied by motor impairments or motivational loss even when dopamine receptors in the dorsal hippocampus were selectively blocked. Stimulation of VTA dopaminergic axons within the dorsal hippocampus enhanced the mice's ability to adapt to changing reward locations. These findings provide insights into the contribution of dopaminergic inputs within the hippocampus to spatial goal adaptation.

The neural representation of time distributed across multiple brain regions differs between implicit and explicit time demands.

Animals appear to possess an internal timer during action, based on the passage of time. However, the neural underpinnings of the perception of time, ranging from seconds to minutes, remain unclear. Herein, we considered the neural representation of time based on mounting evidence on the neural correlates of time perception. The passage of time in the brain is represented by two types of neural encoding as follows: (i) the modulation of firing rates in single neurons and (ii) the sequential activity in neural ensembles. Time-dependent neural activity reflects the relative time rather than the absolute time, similar to a clock. They emerge in multiple regions, including the hippocampus, medial and lateral entorhinal cortices, medial prefrontal cortex, and dorsal striatum. Moreover, they involve different brain regions, depending on an implicit or explicit event duration. Thus, the two types of internal timers distributed across multiple brain regions simultaneously engage in time perception, in response to implicit or explicit time demands.

Utilizing a Reconfigurable Maze System to Enhance the Reproducibility of Spatial Navigation Tests in Rodents.

Several maze shapes are used to test spatial navigation performance and behavioral phenotypes. Traditionally, each experiment requires a unique maze shape, thus requiring several separate mazes in different configurations. The maze geometry cannot be reconfigured in a single environment to accommodate scalability and reproducibility. The reconfigurable maze is a unique approach to address the limitations, allowing quick and flexible configurations of maze pathways in a repeatable manner. It consists of interlocking pathways and includes feeders, treadmills, movable walls, and shut-off sensors. The current protocol describes how the reconfigurable maze can replicate existing mazes, including the T-shaped, plus-shaped, W-shaped, and figure-eight mazes. Initially, the T-shaped maze was constructed inside a single experimental room, followed by modifications. The rapid and scalable protocol outlined herein demonstrates the flexibility of the reconfigurable maze, achieved through the addition of components and behavioral training phases in a stepwise manner. The reconfigurable maze systematically and precisely assesses the performance of multiple aspects of spatial navigation behavior.

A Review of Neurologgers for Extracellular Recording of Neuronal Activity in the Brain of Freely Behaving Wild Animals.

Simultaneous monitoring of animal behavior and neuronal activity in the brain enables us to examine the neural underpinnings of behaviors. Conventionally, the neural activity data are buffered, amplified, multiplexed, and then converted from analog to digital in the head-stage amplifier, following which they are transferred to a storage server via a cable. Such tethered recording systems, intended for indoor use, hamper the free movement of animals in three-dimensional (3D) space as well as in large spaces or underwater, making it difficult to target wild animals active under natural conditions; it also presents challenges in realizing its applications to humans, such as the Brain-Machine Interfaces (BMI). Recent advances in micromachine technology have established a wireless logging device called a neurologger, which directly stores neural activity on ultra-compact memory media. The advent of the neurologger has triggered the examination of the neural correlates of 3D flight, underwater swimming of wild animals, and translocation experiments in the wild. Examples of the use of neurologgers will provide an insight into understanding the neural underpinnings of behaviors in the natural environment and contribute to the practical application of BMI. Here we outline the monitoring of the neural underpinnings of flying and swimming behaviors using neurologgers. We then focus on neuroethological findings and end by discussing their future perspectives.

Head direction cells in a migratory bird prefer north.

Animals exhibit remarkable navigation abilities as if they have an internal compass. Head direction (HD) cells encoding the animal's heading azimuth are found in the brain of several animal species; the HD cell signals are dependent on the vestibular nuclei, where magnetic responsive cells are present in birds. However, it is difficult to determine whether HD cell signals drive the compass orientation in animals, as they do not necessarily rely on the magnetic compass under all circumstances. Recording of HD cell activities from the medial pallium of shearwater chicks (Calonectris leucomelas) just before their first migration, during which they strongly rely on compass orientation, revealed that shearwater HD cells prefer a north orientation. The preference remained stable regardless of geolocations and environmental cues, suggesting the existence of a magnetic compass regulated by internally generated HD signals. Our findings provide insight into the integration of the direction and magnetoreception senses.

Cross-species behavior analysis with attention-based domain-adversarial deep neural networks.

Since the variables inherent to various diseases cannot be controlled directly in humans, behavioral dysfunctions have been examined in model organisms, leading to better understanding their underlying mechanisms. However, because the spatial and temporal scales of animal locomotion vary widely among species, conventional statistical analyses cannot be used to discover knowledge from the locomotion data. We propose a procedure to automatically discover locomotion features shared among animal species by means of domain-adversarial deep neural networks. Our neural network is equipped with a function which explains the meaning of segments of locomotion where the cross-species features are hidden by incorporating an attention mechanism into the neural network, regarded as a black box. It enables us to formulate a human-interpretable rule about the cross-species locomotion feature and validate it using statistical tests. We demonstrate the versatility of this procedure by identifying locomotion features shared across different species with dopamine deficiency, namely humans, mice, and worms, despite their evolutionary differences.

Deep learning-assisted comparative analysis of animal trajectories with DeepHL.

A comparative analysis of animal behavior (e.g., male vs. female groups) has been widely used to elucidate behavior specific to one group since pre-Darwinian times. However, big data generated by new sensing technologies, e.g., GPS, makes it difficult for them to contrast group differences manually. This study introduces DeepHL, a deep learning-assisted platform for the comparative analysis of animal movement data, i.e., trajectories. This software uses a deep neural network based on an attention mechanism to automatically detect segments in trajectories that are characteristic of one group. It then highlights these segments in visualized trajectories, enabling biologists to focus on these segments, and helps them reveal the underlying meaning of the highlighted segments to facilitate formulating new hypotheses. We tested the platform on a variety of trajectories of worms, insects, mice, bears, and seabirds across a scale from millimeters to hundreds of kilometers, revealing new movement features of these animals.

The Reconfigurable Maze Provides Flexible, Scalable, Reproducible, and Repeatable Tests.

Multiple mazes are routinely used to test the performance of animals because each has disadvantages inherent to its shape. However, the maze shape cannot be flexibly and rapidly reproduced in a repeatable and scalable way in a single environment. Here, to overcome the lack of flexibility, scalability, reproducibility, and repeatability, we develop a reconfigurable maze system that consists of interlocking runways and an array of accompanying parts. It allows experimenters to rapidly and flexibly configure a variety of maze structures along the grid pattern in a repeatable and scalable manner. Spatial navigational behavior and hippocampal place coding were not impaired by the interlocking mechanism. As a proof-of-principle demonstration, we demonstrate that the maze morphing induces location remapping of the spatial receptive field. The reconfigurable maze thus provides flexibility, scalability, repeatability, and reproducibility, therefore facilitating consistent investigation into the neuronal substrates for learning and memory and allowing screening for behavioral phenotypes.

Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies.

Uremic pruritus is a very common and frustrating condition for both patients and clinicians because no treatment has been demonstrated to be effective in relieving the itch. In this report, nalfurafine, a new kappa-opioid receptor agonist, was used to treat uremic pruritus in patients who were undergoing routine hemodialysis. Two multicenter, randomized, double-blind, placebo-controlled studies enrolled 144 patients with uremic pruritus to postdialysis intravenous treatment with either nalfurafine or placebo for 2 to 4 wk. A meta-analysis approach was used to assess the efficacy of nalfurafine. Statistically significant reductions in worst itching (P = 0.0212), itching intensity (P = 0.0410), and sleep disturbances (P = 0.0003) were noted in the nalfurafine group as compared with placebo. Improvements in itching (P = 0.0025) and excoriations (P = 0.0060) were noted for the nalfurafine-treated patients. Nalfurafine showed similar types and incidences of drug-related adverse events as did placebo. Nalfurafine was shown to be an effective and safe compound for use in this severely ill patient population.