Advances in cellular resolution microscopy for brain imaging in rats.

Rats are used in neuroscience research because of their physiological similarities with humans and accessibility as model organisms, trainability, and behavioral repertoire. In particular, rats perform a wide range of sophisticated social, cognitive, motor, and learning behaviors within the contexts of both naturalistic and laboratory environments. Further progress in neuroscience can be facilitated by using advanced imaging methods to measure the complex neural and physiological processes during behavior in rats. However, compared with the mouse, the rat nervous system offers a set of challenges, such as larger brain size, decreased neuron density, and difficulty with head restraint. Here, we review recent advances in in vivo imaging techniques in rats with a special focus on open-source solutions for calcium imaging. Finally, we provide suggestions for both users and developers of in vivo imaging systems for rats.

No Differences in Exercise Performance, Perceptual Response, or Safety Were Observed Among 3 Blood Flow Restriction Devices.

Purpose: To compare 3 separate blood flow restriction (BFR) systems in their capacity to reduce repetitions to failure, impact perceptual responses, and cause adverse events during a low-load free-flow exercise. Methods: The study included healthy subjects aged 18 years or older who presented to an ambulatory-care sports medicine clinic. On day 1, participants' demographic characteristics and anthropomorphic measurements were recorded. Each participant performed dumbbell biceps curl repetitions to failure using 20% of his or her 1-repetition maximum weight with each arm. Participants were exposed to 3 different tourniquet systems for familiarization. On day 2, each participant's arm was randomized to a cuff system, and the participant performed 2 sets of biceps curl repetitions to failure with the cuff inflated. Repetitions to failure, rating of perceived effort (RPE), rating of perceived discomfort, and pulse oxygenation levels were recorded after each set. On day 3, participants completed a survey of their perceived delayed-onset muscle soreness. Results: The final analysis was performed on 42 arms, with 14 limbs per system. The study population had a mean age of 28.7 ± 2.4 years and a mean body mass index of 24.9 ± 4.3. All 3 systems successfully reduced repetitions to failure compared with unrestricted low-load exercise from baseline to BFR set 1 and from baseline to BFR set 2. There were no significant between-group differences among BFR systems regarding the number of repetitions to failure performed at baseline versus BFR set 1 or BFR set 2. The Delfi Personalized Tourniquet System (PTS) cohort had the greatest reductions in repetitions to failure from BFR set 1 to BFR set 2 (P = .002) and reported the highest RPE after set 2 (P = .025). Conclusions: The Delfi PTS, SmartCuffs Pro, and BStrong BFR systems were each safe and were able to significantly reduce repetitions to failure compared with a low-load free-flow condition when used in a BFR exercise protocol. The Delfi PTS system may produce a higher RPE with prolonged use in comparison to the other systems. Level of Evidence: Level II, prospective cohort study.

Spatial navigation: A touch in the dark.

New work reveals whisker landmark coding in the retrosplenial cortex of mice, broadening our understanding of multisensory spatial cognition, contextual processing, and spatial predictive coding.

Gluteal Tendinopathy: Critical Analysis Review of Current Nonoperative Treatments.

¼ Gluteal tendinopathy/greater trochanteric pain syndrome (GTPS) is the most prevalent of all lower limb tendinopathies, affecting 1 in 4 women older than 50 years and commonly individuals within their fifth and sixth decades of life regardless of activity level.¼ The condition is believed to originate from age-related degenerative changes about the hip abductor tendon insertions and the surrounding bursae, and is exacerbated by congenital and acquired abnormal hip biomechanics.¼ Treatment of gluteal tendinopathy/GTPS often begins with noninvasive nonoperative modalities such as activity modifications, nonsteroidal anti-inflammatory drugs, and physical therapy. For recalcitrant symptoms, additional nonoperative therapies have been used; however, there remains a lack of comparative efficacy between these adjunct treatments.¼ In this article, we examine the available literature regarding the nonoperative management of gluteal tendinopathy/GTPS and provide insight into the effectiveness of current treatment modalities.

Learning the Vector Coding of Egocentric Boundary Cells from Visual Data.

The use of spatial maps to navigate through the world requires a complex ongoing transformation of egocentric views of the environment into position within the allocentric map. Recent research has discovered neurons in retrosplenial cortex and other structures that could mediate the transformation from egocentric views to allocentric views. These egocentric boundary cells respond to the egocentric direction and distance of barriers relative to an animal's point of view. This egocentric coding based on the visual features of barriers would seem to require complex dynamics of cortical interactions. However, computational models presented here show that egocentric boundary cells can be generated with a remarkably simple synaptic learning rule that forms a sparse representation of visual input as an animal explores the environment. Simulation of this simple sparse synaptic modification generates a population of egocentric boundary cells with distributions of direction and distance coding that strikingly resemble those observed within the retrosplenial cortex. Furthermore, some egocentric boundary cells learnt by the model can still function in new environments without retraining. This provides a framework for understanding the properties of neuronal populations in the retrosplenial cortex that may be essential for interfacing egocentric sensory information with allocentric spatial maps of the world formed by neurons in downstream areas, including the grid cells in entorhinal cortex and place cells in the hippocampus.SIGNIFICANCE STATEMENT The computational model presented here demonstrates that the recently discovered egocentric boundary cells in retrosplenial cortex can be generated with a remarkably simple synaptic learning rule that forms a sparse representation of visual input as an animal explores the environment. Additionally, our model generates a population of egocentric boundary cells with distributions of direction and distance coding that strikingly resemble those observed within the retrosplenial cortex. This transformation between sensory input and egocentric representation in the navigational system could have implications for the way in which egocentric and allocentric representations interface in other brain areas.

Gated transformations from egocentric to allocentric reference frames involving retrosplenial cortex, entorhinal cortex, and hippocampus.

This paper reviews the recent experimental finding that neurons in behaving rodents show egocentric coding of the environment in a number of structures associated with the hippocampus. Many animals generating behavior on the basis of sensory input must deal with the transformation of coordinates from the egocentric position of sensory input relative to the animal, into an allocentric framework concerning the position of multiple goals and objects relative to each other in the environment. Neurons in retrosplenial cortex show egocentric coding of the position of boundaries in relation to an animal. These neuronal responses are discussed in relation to existing models of the transformation from egocentric to allocentric coordinates using gain fields and a new model proposing transformations of phase coding that differ from current models. The same type of transformations could allow hierarchical representations of complex scenes. The responses in rodents are also discussed in comparison to work on coordinate transformations in humans and non-human primates.

Epidemiology of Lateral Ligament Complex Tears of the Ankle in National Collegiate Athletic Association (NCAA) Sports: 2014-15 Through 2018-19.

BACKGROUND: Epidemiological studies of lateral ankle sprains in NCAA sports are important in appraising the burden of this injury and informing prevention efforts. PURPOSE: To describe the epidemiology of lateral ankle sprains in NCAA sports during the 2014-15 through 2018-19 seasons. STUDY DESIGN: Descriptive epidemiology study. METHODS: Injury and exposure information collected within the NCAA Injury Surveillance Program (ISP) were examined. Counts, rates, and proportions of lateral ankle sprains were used to describe injury incidence by sport, event type (practices, competitions), season segment (preseason, regular season, postseason), injury mechanism (player contact, noncontact, and surface contact, injury history (new, recurrent), and time loss (time loss [≥1 day], non-time loss). Injury rate ratios (IRRs) were used to examine differential injury rates, and injury proportion ratios (IPRs) were used to examine differential distributions. RESULTS: A total of 3910 lateral ankle sprains were reported (4.61 per 10,000 athlete exposures) during the study period, and the overall rate was highest in men's basketball (11.82 per 10,000 athlete exposures). The competition-related injury rate was higher than the practice-related rate (IRR, 3.24; 95% CI, 3.04-3.45), and across season segments, the overall rate was highest in preseason (4.99 per 10,000 athlete exposures). Lateral ankle sprains were most often attributed to player-contact mechanisms in men's (43.2%) and women's sports (35.1%), although injuries were more prevalently attributed to player contact in men's than in women's sports (IPR, 1.23; 95% CI, 1.13-1.34). Overall, 49.7% of all lateral ankle sprains were time loss injuries. CONCLUSIONS: The findings of this study are consistent with previous epidemiological investigations of lateral ankle sprains among NCAA athletes. Results offer additional context on differential injury mechanisms between men's and women's sports and on injury risk across the competitive season. Future research may examine the effectiveness of deploying injury prevention programs before the start of a season.

Rethinking retrosplenial cortex: Perspectives and predictions.

The last decade has produced exciting new ideas about retrosplenial cortex (RSC) and its role in integrating diverse inputs. Here, we review the diversity in forms of spatial and directional tuning of RSC activity, temporal organization of RSC activity, and features of RSC interconnectivity with other brain structures. We find that RSC anatomy and dynamics are more consistent with roles in multiple sensorimotor and cognitive processes than with any isolated function. However, two more generalized categories of function may best characterize roles for RSC in complex cognitive processes: (1) shifting and relating perspectives for spatial cognition and (2) prediction and error correction for current sensory states with internal representations of the environment. Both functions likely take advantage of RSC's capacity to encode conjunctions among sensory, motor, and spatial mapping information streams. Together, these functions provide the scaffold for intelligent actions, such as navigation, perspective taking, interaction with others, and error detection.

Adaptive integration of self-motion and goals in posterior parietal cortex.

Rats readily switch between foraging and more complex navigational behaviors such as pursuit of other rats or prey. These tasks require vastly different tracking of multiple behaviorally significant variables including self-motion state. To explore whether navigational context modulates self-motion tracking, we examined self-motion tuning in posterior parietal cortex neurons during foraging versus visual target pursuit. Animals performing the pursuit task demonstrate predictive processing of target trajectories by anticipating and intercepting them. Relative to foraging, pursuit yields multiplicative gain modulation of self-motion tuning and enhances self-motion state decoding. Self-motion sensitivity in parietal cortex neurons is, on average, history dependent regardless of behavioral context, but the temporal window of self-motion integration extends during target pursuit. Finally, many self-motion-sensitive neurons conjunctively track the visual target position relative to the animal. Thus, posterior parietal cortex functions to integrate the location of navigationally relevant target stimuli into an ongoing representation of past, present, and future locomotor trajectories.

Neural responses in retrosplenial cortex associated with environmental alterations.

The retrosplenial cortex (RSC) is an area interconnected with regions of the brain that display spatial correlates. Neurons in connected regions may encode an animal's position in the environment and location or proximity to objects or boundaries. RSC has also been shown to be important for spatial memory, such as tracking distance from and between landmarks, contextual information, and orientation within an environment. For these reasons, it is important to determine how neurons in RSC represent cues such as objects or boundaries and their relationship to the environment. In the current work, we performed electrophysiological recordings in RSC, whereas rats foraged in arenas that could contain an object or in which the environment was altered. We report RSC neurons display changes in mean firing rate responding to alterations of the environment. These alterations include the arena rotating, changing size or shape, or an object being introduced into the arena.

The Unexplored Territory of Neural Models: Potential Guides for Exploring the Function of Metabotropic Neuromodulation.

The space of possible neural models is enormous and under-explored. Single cell computational neuroscience models account for a range of dynamical properties of membrane potential, but typically do not address network function. In contrast, most models focused on network function address the dimensions of excitatory weight matrices and firing thresholds without addressing the complexities of metabotropic receptor effects on intrinsic properties. There are many under-explored dimensions of neural parameter space, and the field needs a framework for representing what has been explored and what has not. Possible frameworks include maps of parameter spaces, or efforts to categorize the fundamental elements and molecules of neural circuit function. Here we review dimensions that are under-explored in network models that include the metabotropic modulation of synaptic plasticity and presynaptic inhibition, spike frequency adaptation due to calcium-dependent potassium currents, and afterdepolarization due to calcium-sensitive non-specific cation currents and hyperpolarization activated cation currents. Neuroscience research should more effectively explore possible functional models incorporating under-explored dimensions of neural function.

Neurophysiological coding of space and time in the hippocampus, entorhinal cortex, and retrosplenial cortex.

Neurophysiological recordings in behaving rodents demonstrate neuronal response properties that may code space and time for episodic memory and goal-directed behaviour. Here, we review recordings from hippocampus, entorhinal cortex, and retrosplenial cortex to address the problem of how neurons encode multiple overlapping spatiotemporal trajectories and disambiguate these for accurate memory-guided behaviour. The solution could involve neurons in the entorhinal cortex and hippocampus that show mixed selectivity, coding both time and location. Some grid cells and place cells that code space also respond selectively as time cells, allowing differentiation of time intervals when a rat runs in the same location during a delay period. Cells in these regions also develop new representations that differentially code the context of prior or future behaviour allowing disambiguation of overlapping trajectories. Spiking activity is also modulated by running speed and head direction, supporting the coding of episodic memory not as a series of snapshots but as a trajectory that can also be distinguished on the basis of speed and direction. Recent data also address the mechanisms by which sensory input could distinguish different spatial locations. Changes in firing rate reflect running speed on long but not short time intervals, and few cells code movement direction, arguing against path integration for coding location. Instead, new evidence for neural coding of environmental boundaries in egocentric coordinates fits with a modelling framework in which egocentric coding of barriers combined with head direction generates distinct allocentric coding of location. The egocentric input can be used both for coding the location of spatiotemporal trajectories and for retrieving specific viewpoints of the environment. Overall, these different patterns of neural activity can be used for encoding and disambiguation of prior episodic spatiotemporal trajectories or for planning of future goal-directed spatiotemporal trajectories.

Egocentric boundary vector tuning of the retrosplenial cortex.

The retrosplenial cortex is reciprocally connected with multiple structures implicated in spatial cognition, and damage to the region itself produces numerous spatial impairments. Here, we sought to characterize spatial correlates of neurons within the region during free exploration in two-dimensional environments. We report that a large percentage of retrosplenial cortex neurons have spatial receptive fields that are active when environmental boundaries are positioned at a specific orientation and distance relative to the animal itself. We demonstrate that this vector-based location signal is encoded in egocentric coordinates, is localized to the dysgranular retrosplenial subregion, is independent of self-motion, and is context invariant. Further, we identify a subpopulation of neurons with this response property that are synchronized with the hippocampal theta oscillation. Accordingly, the current work identifies a robust egocentric spatial code in retrosplenial cortex that can facilitate spatial coordinate system transformations and support the anchoring, generation, and utilization of allocentric representations.

Overview of computational models of hippocampus and related structures: Introduction to the special issue.

Extensive computational modeling has focused on the hippocampal formation and associated cortical structures. This overview describes some of the factors that have motivated the strong focus on these structures, including major experimental findings and their impact on computational models. This overview provides a framework for describing the topics addressed by individual articles in this special issue of the journal Hippocampus.

The Role of Hierarchical Dynamical Functions in Coding for Episodic Memory and Cognition.

Behavioral research in human verbal memory function led to the initial definition of episodic memory and semantic memory. A complete model of the neural mechanisms of episodic memory must include the capacity to encode and mentally reconstruct everything that humans can recall from their experience. This article proposes new model features necessary to address the complexity of episodic memory encoding and recall in the context of broader cognition and the functional properties of neurons that could contribute to this broader scope of memory. Many episodic memory models represent individual snapshots of the world with a sequence of vectors, but a full model must represent complex functions encoding and retrieving the relations between multiple stimulus features across space and time on multiple hierarchical scales. Episodic memory involves not only the space and time of an agent experiencing events within an episode but also features shown in neurophysiological data such as coding of speed, direction, boundaries, and objects. Episodic memory includes not only a spatio-temporal trajectory of a single agent but also segments of spatio-temporal trajectories for other agents and objects encountered in the environment consistent with data on encoding the position and angle of sensory features of objects and boundaries. We will discuss potential interactions of episodic memory circuits in the hippocampus and entorhinal cortex with distributed neocortical circuits that must represent all features of human cognition.

Shedding light on stellate cells.

The relationship between grid cells and two types of neurons found in the medial entorhinal cortex has been clarified.

Multiplexed oscillations and phase rate coding in the basal forebrain.

Complex behaviors demand temporal coordination among functionally distinct brain regions. The basal forebrain's afferent and efferent structure suggests a capacity for mediating this coordination at a large scale. During performance of a spatial orientation task, synaptic activity in this region was dominated by four amplitude-independent oscillations temporally organized by the phase of the slowest, a theta-frequency rhythm. Oscillation amplitudes were also organized by task epoch and positively correlated to the task-related modulation of individual neuron firing rates. For many neurons, spiking was temporally organized through phase precession against theta band field potential oscillations. Theta phase precession advanced in parallel to task progression, rather than absolute spatial location or time. Together, the findings reveal a process by which associative brain regions can integrate independent oscillatory inputs and transform them into sequence-specific, rate-coded outputs that are adaptive to the pace with which organisms interact with their environment.

Neurophysiological signatures of temporal coordination between retrosplenial cortex and the hippocampal formation.

Retrosplenial cortex (RSC) is heavily interconnected with a multitude of cortical regions and is directly connected with the hippocampal formation. As such, it is a likely coordinator of information transfer between the hippocampus (HPC) and cortex in the service of spatial cognition and episodic memory. The current work examined three potential temporal frameworks for retrosplenial-hippocampal communication, namely, theta frequency oscillations (6-12 Hz), sharp-wave/ripple events, and repeating, theta phase-locked shifts from low (30-65 Hz) to high (120-160 Hz) gamma frequency oscillations. From simultaneous recordings of single units and local field potentials (LFPs) in RSC and HPC, we report the presence of prominent theta, low-gamma, and high-gamma oscillations in the retrosplenial LFP. Retrosplenial and hippocampal theta rhythms were strongly coherent and subgroups of retrosplenial neurons exhibited either spiking at theta frequencies and/or spike-phase-locking to theta. Retrosplenial neurons were also phase-locked to local low- and high-gamma rhythms, and power in these frequency bands was coupled in a sequential fashion to specific phases of hippocampal and retrosplenial theta rhythms. Coordinated activity between the two regions also occurred during hippocampal sharp-wave/ripple events, where retrosplenial neuron populations were modulated in their spiking and retrosplenial LFPs exhibited sharp-wave-like events that co-occurred with those observed in HPC. These results identify several temporal windows of synchronization between RSC and HPC that may mediate cortico-hippocampal processes related to learning, memory, and spatial representation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Conjunctive coding in an evolved spiking model of retrosplenial cortex.

Retrosplenial cortex (RSC) is an association cortex supporting spatial navigation and memory. However, critical issues remain concerning the forms by which its ensemble spiking patterns register spatial relationships that are difficult for experimental techniques to fully address. We therefore applied an evolutionary algorithmic optimization technique to create spiking neural network models that matched electrophysiologically observed spiking dynamics in rat RSC neuronal ensembles. Virtual experiments conducted on the evolved networks revealed a mixed selectivity coding capability that was not built into the optimization method, but instead emerged as a consequence of replicating biological firing patterns. The experiments reveal several important outcomes of mixed selectivity that may subserve flexible navigation and spatial representation: (a) robustness to loss of specific inputs, (b) immediate and stable encoding of novel routes and route locations, (c) automatic resolution of input variable conflicts, and (d) dynamic coding that allows rapid adaptation to changing task demands without retraining. These findings suggest that biological retrosplenial cortex can generate unique, first-trial, conjunctive encodings of spatial positions and actions that can be used by downstream brain regions for navigation and path integration. Moreover, these results are consistent with the proposed role for the RSC in the transformation of representations between reference frames and navigation strategy deployment. Finally, the specific modeling framework used for evolving synthetic retrosplenial networks represents an important advance for computational modeling by which synthetic neural networks can encapsulate, describe, and predict the behavior of neural circuits at multiple levels of function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Neural mechanisms of navigation involving interactions of cortical and subcortical structures.

Animals must perform spatial navigation for a range of different behaviors, including selection of trajectories toward goal locations and foraging for food sources. To serve this function, a number of different brain regions play a role in coding different dimensions of sensory input important for spatial behavior, including the entorhinal cortex, the retrosplenial cortex, the hippocampus, and the medial septum. This article will review data concerning the coding of the spatial aspects of animal behavior, including location of the animal within an environment, the speed of movement, the trajectory of movement, the direction of the head in the environment, and the position of barriers and objects both relative to the animal's head direction (egocentric) and relative to the layout of the environment (allocentric). The mechanisms for coding these important spatial representations are not yet fully understood but could involve mechanisms including integration of self-motion information or coding of location based on the angle of sensory features in the environment. We will review available data and theories about the mechanisms for coding of spatial representations. The computation of different aspects of spatial representation from available sensory input requires complex cortical processing mechanisms for transformation from egocentric to allocentric coordinates that will only be understood through a combination of neurophysiological studies and computational modeling.