Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations dynamically coupled with hippocampal rhythms across brain states.

The granular retrosplenial cortex (gRSC) exhibits high-frequency oscillations (HFOs; ∼150 Hz), which can be driven by a hippocampus-subiculum pathway. How the cellular-synaptic and laminar organization of gRSC facilitates HFOs is unknown. Here, we probe gRSC HFO generation and coupling with hippocampal rhythms using focal optogenetics and silicon-probe recordings in behaving mice. ChR2-mediated excitation of CaMKII-expressing cells in L2/3 or L5 induces HFOs, but spontaneous HFOs are found only in L2/3, where HFO power is highest. HFOs couple to CA1 sharp wave-ripples (SPW-Rs) during rest and the descending phase of theta. gRSC HFO current sources and sinks are the same for events during both SPW-Rs and theta oscillations. Independent component analysis shows that high gamma (50-100 Hz) in CA1 stratum lacunosum moleculare is comodulated with HFO power. HFOs may thus facilitate interregional communication of a multisynaptic loop between the gRSC, hippocampus, and medial entorhinal cortex during distinct brain and behavioral states.

T-DOpE probes reveal sensitivity of hippocampal oscillations to cannabinoids in behaving mice.

Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. The device tip can be miniaturized (as small as 50 µm) to minimize tissue damage while the ~20 times larger backend allows for industrial-scale connectorization. T-DOpE probes implanted in mouse hippocampus revealed canonical neuronal activity at the level of local field potentials (LFP) and neural spiking. Taking advantage of the triple-functionality of these probes, we monitored LFP while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity (optogenetics). Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit.

Outpatient Oncology Fall Risk: A Quality Improvement Project.

Introduction: Patients receiving cancer treatment are at high risk for falls. No current guidelines or standards of care exist for assessment and prevention of outpatient oncology falls. This quality improvement project's purpose was to 1) describe and evaluate outpatient oncology falls data to determine root cause(s), and develop, implement, and evaluate intervention strategies for future policy refinement, and 2) compare fall rates pre/post implementation of a system-wide Ambulatory Fall Risk Bundle. Methods: Retrospective data were used to describe and categorize fall incidence for the University of Kansas Cancer Center over 12 months. Further analyses were conducted to describe fall rates per 10,000 kept appointments pre/post implementation of an Ambulatory Fall Risk Bundle protocol. Semi-structured interviews were conducted with medical assistants and nurse managers to evaluate the initiative's impact, staff satisfaction, and recommendations for refinement. Results: The initial 12-month assessment yielded 58 patient falls retained for further analyses. Most patients were receiving chemotherapy (46, 79%). Common contributing symptoms included dizziness/ faintness and weakness (25, 43%). Tripping/falling over a hazard (12, 24%) and falls during transfer (10, 5.8%) also were cited. Subsequent analyses of fall rates indicated no change. Recommendations resulting from the qualitative interviews included: orthostatic vital sign protocol implementation, redesign of the electronic medical record fall risk alert, stakeholder involvement in protocol development, staff training, and related patient education strategies, and the procurement of additional assistive devices/equipment. Conclusions: System-related policy and culture change, investment in physical and human resource enhancements, and evidence-based protocols are needed to improve outpatient oncology fall rates.

The validity of a single inertial sensor to assess cervical active range of motion.

Cervical active range of motion (AROM) is an important outcome measure for clinicians working with a range of patient populations, especially people with neck pain. Multi-sensor inertial measurement unit (IMU) devices demonstrate good validity in the research laboratory but are expensive and not easily accessible in clinical settings. The use of single-IMU devices has been proposed but their validity for measuring cervical AROM is unknown. A concurrent and content validity study was conducted, comparing accuracy of single-IMU NeckCare Pro™ with multi-IMU Xsens™ for measuring cervical AROM in healthy adults (8 males, 7 females, mean age 30.6 years [SD 10.4]). Cervical AROM was assessed for flexion, extension, rotation (right and left), and lateral flexion (right and left), whereby six repetitions were performed for each movement with the subjects strapped to a high-back chair. Regarding content validity, Xsens™ detected a small amount of thoracic movement that could not be detected by the NeckCare Pro™ during cervical AROM testing, with means ranging from 1.5° to 4.1°. However, this did not significantly impact concurrent validity, which was good for all movements (ICC 0.764 - 0.966). This paper found that single-IMU technology (NeckCare Pro™) had good validity for measuring cervical AROM in healthy adults when subjects were strapped to a chair to limit trunk movement.

Submillimeter Multifunctional Ferromagnetic Fiber Robots for Navigation, Sensing, and Modulation.

Small-scale robots capable of remote active steering and navigation offer great potential for biomedical applications. However, the current design and manufacturing procedure impede their miniaturization and integration of various diagnostic and therapeutic functionalities. Herein, submillimeter fiber robots that can integrate navigation, sensing, and modulation functions are presented. These fiber robots are fabricated through a scalable thermal drawing process at a speed of 4 meters per minute, which enables the integration of ferromagnetic, electrical, optical, and microfluidic composite with an overall diameter of as small as 250 µm and a length of as long as 150 m. The fiber tip deflection angle can reach up to 54o under a uniform magnetic field of 45 mT. These fiber robots can navigate through complex and constrained environments, such as artificial vessels and brain phantoms. Moreover, Langendorff mouse hearts model, glioblastoma micro platforms, and in vivo mouse models are utilized to demonstrate the capabilities of sensing electrophysiology signals and performing a localized treatment. Additionally, it is demonstrated that the fiber robots can serve as endoscopes with embedded waveguides. These fiber robots provide a versatile platform for targeted multimodal detection and treatment at hard-to-reach locations in a minimally invasive and remotely controllable manner.

Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations coupled with hippocampal theta and gamma in online states or sharp-wave ripples in offline states.

Neuronal oscillations support information transfer by temporally aligning the activity of anatomically distributed 'writer' and 'reader' cell assemblies. High-frequency oscillations (HFOs) such as hippocampal CA1 sharp-wave ripples (SWRs; 100-250 Hz) are sufficiently fast to initiate synaptic plasticity between assemblies and are required for memory consolidation. HFOs are observed in parietal and midline cortices including granular retrosplenial cortex (gRSC). In 'offline' brain states (e.g. quiet wakefulness) gRSC HFOs co-occur with CA1 SWRs, while in 'online' states (e.g. ambulation) HFOs persist with the emergence of theta oscillations. The mechanisms of gRSC HFO oscillations, specifically whether the gRSC can intrinsically generate HFOs, and which layers support HFOs across states, remain unclear. We addressed these issues in behaving mice using optogenetic excitation in individual layers of the gRSC and high density silicon-probe recordings across gRSC layers and hippocampus CA1. Optogenetically induced HFOs (iHFOs) could be elicited by depolarizing excitatory neurons with 100 ms half-sine wave pulses in layer 2/3 (L2/3) or layer 5 (L5) though L5 iHFOs were of lower power than in L2/3. Critically, spontaneous HFOs were only observed in L2/3 and never in L5. Intra-laminar monosynaptic connectivity between excitatory and inhibitory neurons was similar across layers, suggesting other factors restrict HFOs to L2/3. To compare HFOs in online versus offline states we analyzed, separately, HFOs that did or did not co-occur with CA1 SWRs. Using current-source density analysis we found uniform synaptic inputs to L2/3 during all gRSC HFOs, suggesting layer-specific inputs may dictate the localization of HFOs to L2/3. HFOs occurring without SWRs were aligned with the descending phase of both gRSC and CA1 theta oscillations and were coherent with CA1 high frequency gamma oscillations (50-80 Hz). These results demonstrate that gRSC can internally generate HFOs without rhythmic inputs and that HFOs occur exclusively in L2/3, coupled to distinct hippocampal oscillations in online versus offline states.

Tapered Drug delivery, Optical stimulation, and Electrophysiology (T-DOpE) probes reveal the importance of cannabinoid signaling in hippocampal CA1 oscillations in behaving mice.

Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. Here we developed a thermal tapering process (TTP) which enables the fabrication of novel, low-cost, flexible probes that combine ultrafine features of dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly of the probes. We demonstrate that our T-DOpE ( T apered D rug delivery, Op tical stimulation, and E lectrophysiology) probe achieves in a single neuron-scale device (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. With a tapered geometry, the device tip can be minimized (as small as 50 µm) to ensure minimal tissue damage while the backend is ~20 times larger allowing for direct integration with industrial-scale connectorization. Acute and chronic implantation of the probes in mouse hippocampus CA1 revealed canonical neuronal activity at the level of local field potentials and spiking. Taking advantage of the triple-functionality of the T-DOpE probe, we monitored local field potentials with simultaneous manipulation of endogenous type 1 cannabinoid receptors (CB1R; via microfluidic agonist delivery) and CA1 pyramidal cell membrane potential (optogenetic activation). Electro-pharmacological experiments revealed that focal infusion of CB1R agonist CP-55,940 in dorsal CA1 downregulated theta and sharp wave-ripple oscillations. Furthermore, using the full electro-pharmacological-optical feature set of the T-DOpE probe we found that CB1R activation reduces sharp wave-ripples (SPW-Rs) by impairing the innate SPW-R-generating ability of the CA1 circuit.

Understanding the Cures Act Information Blocking Rule in cancer care: a mixed methods exploration of patient and clinician perspectives and recommendations for policy makers.

BACKGROUND: The 21st Century Cures Act Interoperability and Information Blocking Rule was created to increase patient access to health information. This federally mandated policy has been met with praise and concern. However, little is known about patient and clinician opinions of this policy within cancer care. METHODS: We conducted a convergent parallel mixed methods study to understand patient and clinician reactions to the Information Blocking Rule in cancer care and what they would like policy makers to consider. Twenty-nine patients and 29 clinicians completed interviews and surveys. Inductive thematic analysis was used to analyze the interviews. Interview and survey data were analyzed separately, then linked to generate a full interpretation of the results. RESULTS: Overall, patients felt more positive about the policy than clinicians. Patients wanted policy makers to understand that patients are unique, and they want to individualize their preferences for receiving health information with their clinicians. Clinicians highlighted the uniqueness of cancer care, due to the highly sensitive information that is shared. Both patients and clinicians were concerned about the impact on clinician workload and stress. Both expressed an urgent need for tailoring implementation of the policy to avoid unintended harm and distress for patients. CONCLUSIONS: Our findings provide suggestions for optimizing the implementation of this policy in cancer care. Dissemination strategies to better inform the public about the policy and improve clinician understanding and support are recommended. Patients who have serious illness or diagnoses such as cancer and their clinicians should be included when developing and enacting policies that could have a significant impact on their well-being. Patients with cancer and their cancer care teams want the ability to tailor information release based on individual preferences and goals. Understanding how to tailor implementation of the Information Blocking Rule is essential for retaining its benefits and minimizing unintended harm for patients with cancer.

Hippocampal sharp wave-ripple dynamics in NREM sleep encode motivation for anticipated physical activity.

Physical activity is an integral part of every mammal's daily life, and as a driver of Darwinian fitness, required coordinated evolution of the body and brain. The decision to engage in physical activity is driven either by survival needs or by motivation for the rewarding qualities of physical activity itself. Rodents exhibit innate and learned motivation for voluntary wheel running, and over time run longer and farther, reflecting increased incentive salience and motivation for this consummatory behavior. Dynamic coordination of neural and somatic physiology are necessary to ensure the ability to perform behaviors that are motivationally variable. Hippocampal sharp wave-ripples (SWRs) have evolved both cognitive and metabolic functions, which in modern mammals may facilitate body-brain coordination. To determine if SWRs encode aspects of exercise motivation we monitored hippocampal CA1 SWRs and running behaviors in adult mice, while manipulating the incentive salience of the running experience. During non-REM (NREM) sleep, the duration of SWRs before (but not after) running positively correlated with future running duration, and larger pyramidal cell assemblies were activated in longer SWRs, suggesting that the CA1 network encodes exercise motivation at the level of neuronal spiking dynamics. Inter-Ripple-intervals (IRI) before but not after running were negatively correlated with running duration, reflecting more SWR bursting, which increases with learning. In contrast, SWR rates before and after running were positively correlated with running duration, potentially reflecting a tuning of metabolic demand for that day's anticipated and actual energy expenditure rather than motivation. These results suggest a novel role for CA1 in exercise behaviors and specifically that cell assembly activity during SWRs encodes motivation for anticipated physical activity. SIGNIFICANCE STATEMENT: Darwinian fitness is increased by body-brain coordination through internally generated motivation, though neural substrates are poorly understood. Specific hippocampal rhythms (i.e., CA1 SWRs), which have a well-established role in reward learning, action planning and memory consolidation, have also been shown to modulate systemic [glucose]. Using a mouse model of voluntary physical activity that requires body-brain coordination, we monitored SWR dynamics when animals were highly motivated and anticipated rewarding exercise (i.e., when body-brain coordination is of heightened importance). We found that during non-REM sleep before exercise, SWR dynamics (which reflect cognitive and metabolic functions) were correlated with future time spent exercising. This suggests that SWRs support cognitive and metabolic facets that motivate behavior by coordinating the body and brain.

Multifunctional ferromagnetic fiber robots for navigation, sensing, and treatment in minimally invasive surgery.

Small-scale robots capable of remote active steering and navigation offer great potential for biomedical applications. However, the current design and manufacturing procedure impede their miniaturization and integration of various diagnostic and therapeutic functionalities. Here, we present a robotic fiber platform for integrating navigation, sensing, and therapeutic functions at a submillimeter scale. These fiber robots consist of ferromagnetic, electrical, optical, and microfluidic components, fabricated with a thermal drawing process. Under magnetic actuation, they can navigate through complex and constrained environments, such as artificial vessels and brain phantoms. Moreover, we utilize Langendorff mouse hearts model, glioblastoma microplatforms, and in vivo mouse models to demonstrate the capabilities of sensing electrophysiology signals and performing localized treatment. Additionally, we demonstrate that the fiber robots can serve as endoscopes with embedded waveguides. These fiber robots provide a versatile platform for targeted multimodal detection and treatment at hard-to-reach locations in a minimally invasive and remotely controllable manner.

Dispositional mindfulness and its relationship to exercise motivation and experience.

Mindfulness is the psychological state of staying attuned to the present moment, without ruminating on past or future events, and allowing thoughts, feelings, or sensations to arise without judgment or attachment. Previous work has shown that heightened dispositional mindfulness is associated with the awareness of the importance of exercise, exercise self-efficacy, exercise motivation, and self-reported exercise level. However, more methodologically rigorous studies are needed to understand the relationship between mindfulness and the psychological mechanisms related to exercise motivation, including the identification of why individuals are motivated to engage in exercise, the subjective experience of exercise, and the propensity for exercise dependence and addiction. In this cross-sectional investigation, we utilized the framework of the Self-Determination Theory to examine the hypothesis that heightened dispositional mindfulness (as measured by the Mindful Attention Awareness Scale) would be associated with increased levels of exercise motivation that were derived by higher levels of autonomous self-regulation. Individuals were recruited from urban areas who self-reported either low (exercising 2 or fewer times per week for 20 min or less; n = 78) or moderate (exercising 1 or 2 times per week for 20 min or more; n = 127) levels of exercise engagement. As hypothesized, heightened dispositional mindfulness was significantly associated with heightened levels of exercise self-determination as measured by the Behavioral Regulations in Exercise Questionnaire, with this effect being driven by negative associations with amotivation, external regulation, and introjected regulation. Additionally, we found that heightened dispositional mindfulness was associated with lower levels of psychological distress upon exercise and decreased exercise dependence/addiction. Overall, increased dispositional mindfulness may support a healthy relationship with exercise. These findings have implications for the utility of mindfulness interventions to support the regulation of exercise behaviors in service of enhancing exercise motivation and engagement.

Reliability of Cervicocephalic Proprioception Assessment: A Systematic Review.

OBJECTIVE: The purpose of this systematic review was to determine the reliability and, where possible, the validity of cervicocephalic proprioceptive (CCP) tests in healthy adults and clinical populations. METHODS: A systematic search, utilizing 7 databases from the earliest possible date to April 14, 2021, identified studies that measured reliability of CCP tests. Studies were screened for eligibility, and included studies were appraised using Quality Appraisal Tool for Studies of Diagnostic Reliability (QAREL) and Quality Assessment and Diagnostic Accuracy Studies-2 Tool (QUADAS-2) tools. Validity outcomes were assessed for included studies. RESULTS: Of 34 included studies, 29 investigated reliability for sense of position tests, 10 involved sense of movement tests, and 1 used a sense of force test. The head to neutral test was reliable and valid when 6 or more repetitions were performed within the test, discriminating between those with and without neck pain. Head tracking tests were reliable with 6 repetitions, and 1 study found discriminative validity in a whiplash population. Studies that found discriminative validity in sense of position reported mean joint position error generally >4.5° in the neck pain group and <4.5° in the asymptomatic group. No sense of force test was applied to a clinical population. Convergent validity analysis showed that these proprioceptive tests have low correlations with each other. CONCLUSION: The reliability and validity of CCP tests for sense of position and movement are dependent upon equipment and repetitions. Six repetitions are generally required for good reliability, and joint position error >4.5° is likely to indicate impairment in sense of position.

Recruitment and inhibitory action of hippocampal axo-axonic cells during behavior.

The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the "chandelier" or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting the initial segment, their in vivo activity patterns and influence over pyramidal cell dynamics are not well understood. We achieved cell-type-specific genetic access to AACs in mice and show that AACs in the hippocampal area CA1 are synchronously activated by episodes of locomotion or whisking during rest. Bidirectional intervention experiments in head-restrained mice performing a random foraging task revealed that AACs inhibit CA1 pyramidal cells, indicating that the effect of GABA on the initial segments in the hippocampus is inhibitory in vivo. Finally, optogenetic inhibition of AACs at specific track locations induced remapping of pyramidal cell place fields. These results demonstrate brain-state-specific dynamics of a critical inhibitory controller of cortical circuits.

Preexisting hippocampal network dynamics constrain optogenetically induced place fields.

Memory models often emphasize the need to encode novel patterns of neural activity imposed by sensory drive. Prior learning and innate architecture likely restrict neural plasticity, however. Here, we test how the incorporation of synthetic hippocampal signals is constrained by preexisting circuit dynamics. We optogenetically stimulated small groups of CA1 neurons as mice traversed a chosen segment of a linear track, mimicking the emergence of place fields. Stimulation induced persistent place field remapping in stimulated and non-stimulated neurons. The emergence of place fields could be predicted from sporadic firing in the new place field location and the temporal relationship to peer neurons before the optogenetic perturbation. Circuit modification was reflected by altered spike transmission between connected pyramidal cells and inhibitory interneurons, which persisted during post-experience sleep. We hypothesize that optogenetic perturbation unmasked sub-threshold place fields. Plasticity in recurrent/lateral inhibition may drive learning through the rapid association of existing states.

Monosynaptic inference via finely-timed spikes.

Observations of finely-timed spike relationships in population recordings have been used to support partial reconstruction of neural microcircuit diagrams. In this approach, fine-timescale components of paired spike train interactions are isolated and subsequently attributed to synaptic parameters. Recent perturbation studies strengthen the case for such an inference, yet the complete set of measurements needed to calibrate statistical models is unavailable. To address this gap, we study features of pairwise spiking in a large-scale in vivo dataset where presynaptic neurons were explicitly decoupled from network activity by juxtacellular stimulation. We then construct biophysical models of paired spike trains to reproduce the observed phenomenology of in vivo monosynaptic interactions, including both fine-timescale spike-spike correlations and firing irregularity. A key characteristic of these models is that the paired neurons are coupled by rapidly-fluctuating background inputs. We quantify a monosynapse's causal effect by comparing the postsynaptic train with its counterfactual, when the monosynapse is removed. Subsequently, we develop statistical techniques for estimating this causal effect from the pre- and post-synaptic spike trains. A particular focus is the justification and application of a nonparametric separation of timescale principle to implement synaptic inference. Using simulated data generated from the biophysical models, we characterize the regimes in which the estimators accurately identify the monosynaptic effect. A secondary goal is to initiate a critical exploration of neurostatistical assumptions in terms of biophysical mechanisms, particularly with regards to the challenging but arguably fundamental issue of fast, unobservable nonstationarities in background dynamics.

Anopheline and human drivers of malaria risk in northern coastal, Ecuador: a pilot study.

BACKGROUND: Understanding local anopheline vector species and their bionomic traits, as well as related human factors, can help combat gaps in protection. METHODS: In San José de Chamanga, Esmeraldas, at the Ecuadorian Pacific coast, anopheline mosquitoes were sampled by both human landing collections (HLCs) and indoor-resting aspirations (IAs) and identified using both morphological and molecular methods. Human behaviour observations (HBOs) (including temporal location and bed net use) were documented during HLCs as well as through community surveys to determine exposure to mosquito bites. A cross-sectional evaluation of Plasmodium falciparum and Plasmodium vivax infections was conducted alongside a malaria questionnaire. RESULTS: Among 222 anopheline specimens captured, based on molecular analysis, 218 were Nyssorhynchus albimanus, 3 Anopheles calderoni (n = 3), and one remains unidentified. Anopheline mean human-biting rate (HBR) outdoors was (13.69), and indoors (3.38) (p = 0.006). No anophelines were documented resting on walls during IAs. HBO-adjusted human landing rates suggested that the highest risk of being bitten was outdoors between 18.00 and 20.00 h. Human behaviour-adjusted biting rates suggest that overall, long-lasting insecticidal bed nets (LLINs) only protected against 13.2% of exposure to bites, with 86.8% of exposure during the night spent outside of bed net protection. The malaria survey found 2/398 individuals positive for asymptomatic P. falciparum infections. The questionnaire reported high (73.4%) bed net use, with low knowledge of malaria. CONCLUSION: The exophagic feeding of anopheline vectors in San Jose de Chamanga, when analysed in conjunction with human behaviour, indicates a clear gap in protection even with high LLIN coverage. The lack of indoor-resting anophelines suggests that indoor residual spraying (IRS) may have limited effect. The presence of asymptomatic infections implies the presence of a human reservoir that may maintain transmission.

Publisher Correction: Propagation of hippocampal ripples to the neocortex by way of a subiculum-retrosplenial pathway.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Gluteus medius and minimus activity during stepping tasks: Comparisons between people with hip osteoarthritis and matched control participants.

BACKGROUND: Altered gluteus minimus (GMin) activity has been identified in people with hip osteoarthritis (OA) during gait with some evidence of altered gluteus medius (GMed) activity in patients with advanced OA. It is not known whether these muscles also exhibit altered activity during other functional tasks. RESEARCH QUESTION: Does gluteal muscle activity during stepping tasks differ between people with hip OA and healthy older adults? METHODS: Participants included 20 people with unilateral hip OA and 20 age-and sex-matched controls. Muscle activity in the three segments within GMed and two segments of GMin were examined using intramuscular electromyography during step-up, step-down and side-step tasks. RESULTS: Participants in the OA group demonstrated reduced muscle activity early in the step-up task and a later time to peak activity in most muscle segments. Greater activity was identified in anterior GMin in people with hip OA during the side-step task. A delay in time to peak activity was identified in most muscle segments in people with OA during the side-step task. SIGNIFICANCE: For participants with OA, reduced activity in most muscle segments and increased time spent in double limb stance during the step-up task could reflect the decreased strength and pain associated with single limb stance on the affected limb. This study provides further evidence of altered function of the deep gluteal muscles in people with hip OA and highlights the importance of addressing these muscles in rehabilitation.

Propagation of hippocampal ripples to the neocortex by way of a subiculum-retrosplenial pathway.

Bouts of high frequency activity known as sharp wave ripples (SPW-Rs) facilitate communication between the hippocampus and neocortex. However, the paths and mechanisms by which SPW-Rs broadcast their content are not well understood. Due to its anatomical positioning, the granular retrosplenial cortex (gRSC) may be a bridge for this hippocampo-cortical dialogue. Using silicon probe recordings in awake, head-fixed mice, we show the existence of SPW-R analogues in gRSC and demonstrate their coupling to hippocampal SPW-Rs. gRSC neurons reliably distinguished different subclasses of hippocampal SPW-Rs according to ensemble activity patterns in CA1. We demonstrate that this coupling is brain state-dependent, and delineate a topographically-organized anatomical pathway via VGlut2-expressing, bursty neurons in the subiculum. Optogenetic stimulation or inhibition of bursty subicular cells induced or reduced responses in superficial gRSC, respectively. These results identify a specific path and underlying mechanisms by which the hippocampus can convey neuronal content to the neocortex during SPW-Rs.