Predictive learning by a burst-dependent learning rule.

Humans and other animals are able to quickly generalize latent dynamics of spatiotemporal sequences, often from a minimal number of previous experiences. Additionally, internal representations of external stimuli must remain stable, even in the presence of sensory noise, in order to be useful for informing behavior. In contrast, typical machine learning approaches require many thousands of samples, and generalize poorly to unexperienced examples, or fail completely to predict at long timescales. Here, we propose a novel neural network module which incorporates hierarchy and recurrent feedback terms, constituting a simplified model of neocortical microcircuits. This microcircuit predicts spatiotemporal trajectories at the input layer using a temporal error minimization algorithm. We show that this module is able to predict with higher accuracy into the future compared to traditional models. Investigating this model we find that successive predictive models learn representations which are increasingly removed from the raw sensory space, namely as successive temporal derivatives of the positional information. Next, we introduce a spiking neural network model which implements the rate-model through the use of a recently proposed biological learning rule utilizing dual-compartment neurons. We show that this network performs well on the same tasks as the mean-field models, by developing intrinsic dynamics that follow the dynamics of the external stimulus, while coordinating transmission of higher-order dynamics. Taken as a whole, these findings suggest that hierarchical temporal abstraction of sequences, rather than feed-forward reconstruction, may be responsible for the ability of neural systems to quickly adapt to novel situations.

Descriptive analysis of horses and ponies attending horse auctions in Victoria from July 2019 to March 2020.

INTRODUCTION: In recent years there has been public speculation about the breed, destination and number of horses being sold by public auction at livestock saleyards in Australia. Currently, there is little objective information available about the breed and condition of horses sold through this medium. With little publicly available objective data on these horses, the horse industry has been left vulnerable to misinformation. Accurate information regarding the composition and condition of horses attending saleyards is important to identify and address any welfare issues and to inform public debate. METHOD: Data were collected on 312 horses and ponies presented for sale through the Pakenham Horse Sales between July 2019 and March 2020. All horses and ponies were inspected at the saleyards and information on breed, age, body condition score (BCS), purchaser and sale price were recorded as the animals were auctioned. RESULTS: Crossbred horses and ponies were the largest groups presented for sale. Ponies were more likely to be sold to private buyers. Quarter horses and riding ponies were as likely to be sent to slaughter as thoroughbreds and standardbreds. Entire males and females sold for lower prices than geldings. Most horses and ponies (64%) were sold to private buyers. More than three-quarters (77%) of horses and ponies presented for sale had a BCS greater than or equal to three out of five. CONCLUSION: This pilot study challenges perceptions that thoroughbreds are the primary breed to attend public sales or that animals attending the sales are in poor condition.

Regulation of human cortical interneuron development by the chromatin remodeling protein CHD2.

Mutations in the chromodomain helicase DNA binding protein 2 (CHD2) gene are associated with neurodevelopmental disorders. However, mechanisms by which CHD2 regulates human brain development remain largely uncharacterized. Here, we used a human embryonic stem cell model of cortical interneuron (hcIN) development to elucidate its roles in this process. We identified genome-wide CHD2 binding profiles during hcIN differentiation, defining direct CHD2 targets related to neurogenesis in hcIN progenitors and to neuronal function in hcINs. CHD2 bound sites were frequently coenriched with histone H3 lysine 27 acetylation (H3K27ac) and associated with high gene expression, indicating roles for CHD2 in promoting gene expression during hcIN development. Binding sites for different classes of transcription factors were enriched at CHD2 bound regions during differentiation, suggesting transcription factors that may cooperatively regulate stage-specific gene expression with CHD2. We also demonstrated that CHD2 haploinsufficiency altered CHD2 and H3K27ac coenrichment on chromatin and expression of associated genes, decreasing acetylation and expression of cell cycle genes while increasing acetylation and expression of neuronal genes, to cause precocious differentiation. Together, these data describe CHD2 direct targets and mechanisms by which CHD2 prevents precocious hcIN differentiation, which are likely to be disrupted by pathogenic CHD2 mutation to cause neurodevelopmental disorders.

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.

The immediate effects of Kinesio Taping on running biomechanics, muscle activity, and perceived changes in comfort, stability and running performance in healthy runners, and the implications to the management of Iliotibial band syndrome.

BACKGROUND: Kinesio Taping is frequently used in the management of lower limb injuries, and has been shown to improve pain, function, and running performance. However, little is known about the effects of Kinesio Taping on running biomechanics, muscle activity, and perceived benefits. RESEARCH QUESTION: This study aimed to explore the immediate effects of Kinesio Taping on lower limb kinematics, joint moments, and muscle activity, as well as perceived comfort, knee joint stability, and running performance in healthy runners. METHODS: Twenty healthy participants ran at a self-selected pace along a 20-metre runway under three conditions; no tape (NT), Kinesio Tape with tension (KTT), and Kinesio tape without tension (KTNT). Comparisons of peak hip, knee angles and moments, and EMG were analysed during the stance phase of running. RESULTS: KTT exhibited significant increases in peak hip flexion, peak hip abduction and hip external rotation compared to NT. Moreover, the KTT condition showed a trend towards a decrease in peak hip internal rotation and adduction angle compared to the NT condition. EMG results showed that Tensor Fascia Latae activity decreased with KTT compared with NT, and Gluteus Maximus activity reduced with KTNT when compared with NT. Ten of the 20 participants indicated important improvements in the comfort score, six participants in the knee stability score, and seven participants in the running performance score when using KTT. SIGNIFICANCE: These results suggest that changes in running biomechanics previously associated with ITBS can be improved with the application of kinesio tape, with the greatest effect seen with the application of kinesio tape with tension. Perceived improvements were seen in comfort, stability and running performance, however these benefits were only seen in half the participants. Further work is required to explore the biomechanical effects and perceived benefits in different patient groups.

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.

Frontal plane knee alignment mediates the effect of frontal plane rearfoot motion on knee joint load distribution during walking in people with medial knee osteoarthritis.

OBJECTIVE: To examine the nature of differences in the relationship between frontal plane rearfoot kinematics and knee adduction moment (KAM) magnitudes. DESIGN: Cross-sectional study resulting from a combination of overground walking biomechanics data obtained from participants with medial tibiofemoral osteoarthritis at two separate sites. Statistical models were created to examine the relationship between minimum frontal plane rearfoot angle (negative values = eversion) and different measures of the KAM, including examination of confounding, mediation, and effect modification from knee pain, radiographic disease severity, static rearfoot alignment, and frontal plane knee angle. RESULTS: Bivariable relationships between minimum frontal plane rearfoot angle and the KAM showed consistent negative correlations (r = -0.411 to -0.447), indicating higher KAM magnitudes associated with the rearfoot in a more everted position during stance. However, the nature of this relationship appears to be mainly influenced by frontal plane knee kinematics. Specifically, frontal plane knee angle during gait was found to completely mediate the relationship between minimum frontal plane rearfoot angle and the KAM, and was also an effect modifier in this relationship. No other variable significantly altered the relationship. CONCLUSIONS: While there does appear to be a moderate relationship between frontal plane rearfoot angle and the KAM, any differences in the magnitude of this relationship can likely be explained through an examination of frontal plane knee angle during walking. This finding suggests that interventions derived distal to the knee should account for the effect of frontal plane knee angle to have the desired effect on the KAM.

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.

Neuronal representation of environmental boundaries in egocentric coordinates.

Movement through space is a fundamental behavior for all animals. Cognitive maps of environments are encoded in the hippocampal formation in an allocentric reference frame, but motor movements that comprise physical navigation are represented within an egocentric reference frame. Allocentric navigational plans must be converted to an egocentric reference frame prior to implementation as overt behavior. Here we describe an egocentric spatial representation of environmental boundaries in the dorsomedial striatum.

Patient characteristics affect hip contact forces during gait.

OBJECTIVE: To examine hip contact force (HCF), calculated through multibody modelling, in a large total hip replacement (THR) cohort stratified by patient characteristics such as body mass index (BMI), age and function. METHOD: 132 THR patients undertook one motion capture session of gait analysis at a self-selected walking speed. HCFs were then calculated using the AnyBody Modelling System. Patients were stratified into three BMI groups, five age groups, and finally three functional groups determined by their self-selected gait speed. By means of statistical parametric mapping (SPM), statistical analyses of the 1-dimensional time series were performed to separately evaluate the influence of age, BMI and functionality on HCF. RESULTS: The mean predicted HCFs were comparable to HCFs measured with instrumented prostheses reported in the literature. The SPM analysis revealed a statistically significant positive linear correlation between BMI and HCF, indicating that obese patients are more likely to experience higher HCF during most of the stance phase, while a statistically significant negative correlation with age was found only during the late swing-phase. Patients with higher functional ability exhibited significantly increased peak HCF, while patients with lower functional ability demonstrated lower HCFs overall and a pathological flattening of the typical double hump force profile. CONCLUSION: HCFs experienced at the bearing surface are highly dependent on patient characteristics. BMI and functional ability were determined to have the biggest influence on contact forces. Current preclinical testing standards do not reflect this.

The challenges posed by equine arboviruses.

Equine populations worldwide are at increasing risk of infection by viruses transmitted by biting arthropods, including mosquitoes, biting midges (Culicoides), sandflies and ticks. These include the flaviviruses (Japanese encephalitis, West Nile and Murray Valley encephalitis), alphaviruses (eastern, western and Venezuelan encephalitis) and the orbiviruses (African horse sickness and equine encephalosis). This review provides an overview of the challenges faced in the surveillance, prevention and control of the major equine arboviruses, particularly in the context of these viruses emerging in new regions of the world.

Systemic administration of two different anxiolytic drugs decreases local field potential theta frequency in the medial entorhinal cortex without affecting grid cell firing fields.

Neurons coding spatial location (grid cells) are found in medial entorhinal cortex (MEC) and demonstrate increasing size of firing fields and spacing between fields (grid scale) along the dorsoventral axis. This change in grid scale correlates with differences in theta frequency, a 6-10Hz rhythm in the local field potential (LFP) and rhythmic firing of cells. A relationship between theta frequency and grid scale can be found when examining grid cells recorded in different locations along the dorsoventral axis of MEC. When describing the relationship between theta frequency and grid scale, it is important to account for the strong positive correlation between theta frequency and running speed. Plotting LFP theta frequency across running speeds dissociates two components of this relationship: slope and intercept of the linear fit. Change in theta frequency through a change in the slope component has been modeled and shown experimentally to affect grid scale, but the prediction that change in the intercept component would not affect grid scale has not been tested experimentally. This prediction about the relationship of intercept to grid scale is the primary hypothesis tested in the experiments presented here. All known anxiolytic drugs decrease hippocampal theta frequency despite their differing mechanisms of action. Specifically, anxiolytics decrease the intercept of the theta frequency-running speed relationship in the hippocampus. Here we demonstrate that anxiolytics decrease the intercept of the theta frequency-running speed relationship in the MEC, similar to hippocampus, and the decrease in frequency through this change in intercept does not affect grid scale.

Post-Inhibitory Rebound Spikes in Rat Medial Entorhinal Layer II/III Principal Cells: In Vivo, In Vitro, and Computational Modeling Characterization.

Medial entorhinal cortex Layer-II stellate cells (mEC-LII-SCs) primarily interact via inhibitory interneurons. This suggests the presence of alternative mechanisms other than excitatory synaptic inputs for triggering action potentials (APs) in stellate cells during spatial navigation. Our intracellular recordings show that the hyperpolarization-activated cation current (Ih) allows post-inhibitory-rebound spikes (PIRS) in mEC-LII-SCs. In vivo, strong inhibitory-post-synaptic potentials immediately preceded most APs shortening their delay and enhancing excitability. In vitro experiments showed that inhibition initiated spikes more effectively than excitation and that more dorsal mEC-LII-SCs produced faster and more synchronous spikes. In contrast, PIRS in Layer-II/III pyramidal cells were harder to evoke, voltage-independent, and slower in dorsal mEC. In computational simulations, mEC-LII-SCs morphology and Ih homeostatically regulated the dorso-ventral differences in PIRS timing and most dendrites generated PIRS with a narrow range of stimulus amplitudes. These results suggest inhibitory inputs could mediate the emergence of grid cell firing in a neuronal network.

Potential vectors of equine arboviruses in the UK.

There is growing concern about the increasing risk of disease outbreaks caused by arthropod-borne viruses (arboviruses) in both human beings and animals. There are several mosquito-borne viral diseases that cause varying levels of morbidity and mortality in horses and that can have substantial welfare and economic ramifications. While none has been recorded in the UK, vector species for some of these viruses are present, suggesting that UK equines may be at risk. The authors undertook, therefore, the first study of mosquito species on equine premises in the UK. Mosquito magnet traps and red-box traps were used to sample adults, and larvae were collected from water sources such as tyres, buckets, ditches and pools. Several species that are known to be capable of transmitting important equine infectious arboviruses were trapped. The most abundant, with a maximum catch of 173 in 72 hours, was Ochlerotatus detritus, a competent vector of some flaviviruses; the highest densities were found near saltmarsh habitats. The most widespread species, recorded at >75 per cent of sites, was Culiseta annulata. This study demonstrates that potential mosquito vectors of arboviruses, including those known to be capable of infecting horses, are present and may be abundant on equine premises in the UK.

Multiple Running Speed Signals in Medial Entorhinal Cortex.

Grid cells in medial entorhinal cortex (MEC) can be modeled using oscillatory interference or attractor dynamic mechanisms that perform path integration, a computation requiring information about running direction and speed. The two classes of computational models often use either an oscillatory frequency or a firing rate that increases as a function of running speed. Yet it is currently not known whether these are two manifestations of the same speed signal or dissociable signals with potentially different anatomical substrates. We examined coding of running speed in MEC and identified these two speed signals to be independent of each other within individual neurons. The medial septum (MS) is strongly linked to locomotor behavior, and removal of MS input resulted in strengthening of the firing rate speed signal, while decreasing the strength of the oscillatory speed signal. Thus, two speed signals are present in MEC that are differentially affected by disrupted MS input.