Cell-type-specific cholinergic control of granular retrosplenial cortex with implications for angular velocity coding across brain states.

Cholinergic receptor activation enables the persistent firing of cortical pyramidal neurons, providing a key cellular basis for theories of spatial navigation involving working memory, path integration, and head direction encoding. The granular retrosplenial cortex (RSG) is important for spatially-guided behaviors, but how acetylcholine impacts RSG neurons is unknown. Here, we show that a transcriptomically, morphologically, and biophysically distinct RSG cell-type - the low-rheobase (LR) neuron - has a very distinct expression profile of cholinergic muscarinic receptors compared to all other neighboring excitatory neuronal subtypes. LR neurons do not fire persistently in response to cholinergic agonists, in stark contrast to all other principal neuronal subtypes examined within the RSG and across midline cortex. This lack of persistence allows LR neuron models to rapidly compute angular head velocity (AHV), independent of cholinergic changes seen during navigation. Thus, LR neurons can consistently compute AHV across brain states, highlighting the specialized RSG neural codes supporting navigation.

Archaeological sites in Grand Canyon National Park along the Colorado River are eroding owing to six decades of Glen Canyon Dam operations.

The archaeological record documenting human history in deserts is commonly concentrated along rivers in terraces or other landforms built by river sediment deposits. Today that record is at risk in many river valleys owing to human resource and infrastructure development activities, including the construction and operation of dams. We assessed the effects of the operations of Glen Canyon Dam - which, since its closure in 1963, has imposed drastic changes to flow, sediment supply and distribution, and riparian vegetation - on a population of 362 archaeological sites in the Colorado River corridor through Grand Canyon National Park, Arizona, USA. We leverage 50 years of evidence from aerial photographs and more than 30 years of field observations and measurements of archaeological-site topography and wind patterns to evaluate changes in the physical integrity of archaeological sites using two geomorphology-based site classification systems. We find that most archaeological sites are eroding; moreover, most are at increased risk of continuing to erode, due to six decades of operations of Glen Canyon Dam. Results show that the wind-driven (aeolian) supply of river-sourced sand, essential for covering archaeological sites and protecting them from erosion, has decreased for most sites since 1973 owing to effects of long-term dam operations on river sediment supply and riparian vegetation expansion on sandbars. Results show that the proportion of sites affected by erosion from gullies controlled by the local base-level of the Colorado River has increased since 2000. These changes to landscape processes affecting archaeological site integrity limit the ability of the National Park Service and Grand Canyon-affiliated Native American Tribes to achieve environmental management goals to maintain or improve site integrity in situ. We identify three environmental management opportunities that could be used to a greater extent to decrease the risk of erosion and increase the potential for in-situ preservation of archaeological sites. Environmental management opportunities are: 1) sediment-rich controlled river floods to increase the aeolian supply of river-sourced sand, 2) extended periods of low river flow to increase the aeolian supply of river-sourced sand, 3) the removal of riparian vegetation barriers to the aeolian transport of river-sourced sand.

Persuasion via Performance: Toward a Handbook for Youth to Develop Content that Promotes HPV Vaccination.

Slightly over half of American teens are fully vaccinated against the human papillomavirus, or HPV. The vaccine is protective against 90% of cancers caused by HPV, including cancers of the vagina, vulva, and cervix in women, the penis in men, and cancers of the throat and anus in both men and women. While HPV vaccination rates are on the rise, rural areas lag significantly behind. There are several reasons why, and there are multiple strategies that can increase vaccination rates. This article discusses the process of creating a writer's handbook to enable youth writers and producers to create provaccination, short-form dramatic stories in podcast format, and to distribute and promote them via social media to their peers. The objective is to prompt students to get their HPV vaccination. The article concludes with examples that will be part of this handbook.

Running speed and REM sleep control two distinct modes of rapid interhemispheric communication.

Rhythmic gamma-band communication within and across cortical hemispheres is critical for optimal perception, navigation, and memory. Here, using multisite recordings in both rats and mice, we show that even faster ∼140 Hz rhythms are robustly anti-phase across cortical hemispheres, visually resembling splines, the interlocking teeth on mechanical gears. Splines are strongest in superficial granular retrosplenial cortex, a region important for spatial navigation and memory. Spline-frequency interhemispheric communication becomes more coherent and more precisely anti-phase at faster running speeds. Anti-phase splines also demarcate high-activity frames during REM sleep. While splines and associated neuronal spiking are anti-phase across retrosplenial hemispheres during navigation and REM sleep, gamma-rhythmic interhemispheric communication is precisely in-phase. Gamma and splines occur at distinct points of a theta cycle and thus highlight the ability of interhemispheric cortical communication to rapidly switch between in-phase (gamma) and anti-phase (spline) modes within individual theta cycles during both navigation and REM sleep.

Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex.

The granular retrosplenial cortex (RSG) is critical for both spatial and non-spatial behaviors, but the underlying neural codes remain poorly understood. Here, we use optogenetic circuit mapping in mice to reveal a double dissociation that allows parallel circuits in superficial RSG to process disparate inputs. The anterior thalamus and dorsal subiculum, sources of spatial information, strongly and selectively recruit small low-rheobase (LR) pyramidal cells in RSG. In contrast, neighboring regular-spiking (RS) cells are preferentially controlled by claustral and anterior cingulate inputs, sources of mostly non-spatial information. Precise sublaminar axonal and dendritic arborization within RSG layer 1, in particular, permits this parallel processing. Observed thalamocortical synaptic dynamics enable computational models of LR neurons to compute the speed of head rotation, despite receiving head direction inputs that do not explicitly encode speed. Thus, parallel input streams identify a distinct principal neuronal subtype ideally positioned to support spatial orientation computations in the RSG.

Sitting in your car, about to drive home after a long day at work, you realize you have no idea which way to go: you recognize where you are right now, and you remember the name of the street your house is on, but you cannot figure out how to get there. This spatial disorientation happens to people with damage to a brain region called the retrosplenial cortex, whose role and inner workings remain poorly understood. Recent evidence has shown that this area contains 'low-rheobase' neurons which are not seen anywhere else in the brain, but what do these neurons do? Brennan, Jedrasiak-Cape, Kailasa et al. decided to explore the role of these neurons, focusing on the brain regions they are connected to. Experiments were conducted in mice using optogenetics, a technique that activates neurons using pulses of light. This revealed that brain areas involved in processing information about direction and position preferentially communicate with low-rheobase neurons rather than with nearby, more standard neurons in the retrosplenial cortex. The way these spatial signals are sent to the low-rheobase neurons allows these cells to 'calculate' how fast a mouse is turning its head using only information about which direction the mouse is facing. Essentially, this neuron can turn directional compass-like signals into a gyroscope signal that can track both direction and speed of head movement. These unique neurons may therefore be ideally suited to combine information about direction and space, suggesting that they may have evolved specifically to support spatial navigation. Individuals with Alzheimer's disease show exactly the same type of spatial disorientation as individuals with direct damage to the retrosplenial cortex. This region is also one of the first to show altered activity in Alzheimer's disease. Exploring whether these unique retrosplenial neurons and their communication patterns are altered in Alzheimer's disease models could help to understand and potentially treat this debilitating condition.

A Pediatric Hospital Physical Therapy and Occupational Therapy Department's Response to COVID-19: An Administrative Case Report.

OBJECTIVE: The purpose of this case report is to describe the challenges that COVID-19 presented for therapists in a pediatric hospital and the response to these challenges. METHODS: The case report setting is a physical therapy and occupational therapy department (department) of an academic pediatric medical center that provides a range of health care services for children and youth. Challenges that COVID-19 presented to the department included (1) managing safety concerns for patients, their families, and staff; (2) continuing to provide high-quality therapy services within state-mandated restrictions; (3) triaging patients; and (4) keeping clinicians employed and working productively. RESULTS: The department therapists responded to these challenges by (1) increasing communication huddles; (2) developing procedures for staffing and triaging of patients; (3) developing procedures for telehealth therapy services; and (4) designing a remote work program for all department employees. The number of patients and staff on site were reduced by initiating telehealth services, triaging patients, and developing a remote work plan. Communication huddles, department meetings, and supervision meetings were converted to virtual meetings. Staffing rates, patient-care productivity, and department project work were maintained. CONCLUSION: In response to COVID-19, the department developed new protocols and provided information about the protocols, which might be helpful for other pediatric hospitals or outpatient settings when planning for future pandemics or other issues that challenge the ability to provide usual care. Increasing the frequency of verbal and written communication on operational topics is recommended. Primary sources of information from national organizations (eg, the American Physical Therapy Association and the American Occupational Therapy Association) can assist with determining the scope of practice and code of conduct during a pandemic. IMPACT: COVID-19 posed challenges to operations and delivery of patient care. Although this case report is specific to COVID-19, principles applied and lessons learned from this experience can be applied to other emergency situations.

A stepped-wedge randomized trial protocol of a community intervention for increasing lung screening through engaging primary care providers (I-STEP).

Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet few eligible high-risk patients receive it annually. This protocol describes a community-partnered intervention (Toolkit) designed to support primary care practices in making referrals for lung screening and guiding patients into appropriate screening pathways. This study uses a stepped-wedge implementation design. Screening centers are randomized by readiness level to enter the intervention phase in three-month "steps" with pre-intervention data serving as the control. The primary outcome is whether delivery of the Toolkit to primary care practices results in a monthly increase in number of initial LDCT screenings. Six participating centers will identify 10 practices and reach 2-3 providers per practice to train them to use the Toolkit. The Toolkit will address known barriers to screening and referral at the patient and provider levels and provide support for required elements of screening. Toolkit components include adaptable evidence-based interventions to maximize compatibility with workflows. We hypothesize that after nine months of intervention delivery, the number of initial screening per center will double. Involving 60 practices achieves 80% power at 5% level of significance. Implementation outcomes such as adoption, acceptability, feasibility, adaptation, and sustainability will be assessed through field-notes and activity logs. LDCT for lung cancer screening currently reaches a small fraction of eligible adults. To reach the full potential to reduce mortality, primary care practices are an important venue for increasing appropriate referrals. This multidisciplinary trial will encourage acceptability and sustainability by using local knowledge and promoting partnership between providers and patients. Trial registration: ClinicalTrials.gov, NCT03958253.

Hyperexcitable Neurons Enable Precise and Persistent Information Encoding in the Superficial Retrosplenial Cortex.

The retrosplenial cortex (RSC) is essential for memory and navigation, but the neural codes underlying these functions remain largely unknown. Here, we show that the most prominent cell type in layers 2/3 (L2/3) of the mouse granular RSC is a hyperexcitable, small pyramidal cell. These cells have a low rheobase (LR), high input resistance, lack of spike frequency adaptation, and spike widths intermediate to those of neighboring fast-spiking (FS) inhibitory neurons and regular-spiking (RS) excitatory neurons. LR cells are excitatory but rarely synapse onto neighboring neurons. Instead, L2/3 is a feedforward, not feedback, inhibition-dominated network with dense connectivity between FS cells and from FS to LR neurons. Biophysical models of LR but not RS cells precisely and continuously encode sustained input from afferent postsubicular head-direction cells. Thus, the distinct intrinsic properties of LR neurons can support both the precision and persistence necessary to encode information over multiple timescales in the RSC.

Ripple While You Walk, and You May Get Lost: Pathological High-Frequency Activity Can Alter Spatial Navigation Circuits.

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Chemoattractant activity of degradation products of fetal and adult skin extracellular matrix for keratinocyte progenitor cells.

Biological scaffolds composed of naturally occurring extracellular matrix (ECM) have been utilized as templates for the constructive remodelling of numerous tissues in preclinical studies and human clinical applications. The mechanisms by which ECM induces constructive remodelling are not well understood, but it appears that the degradation products of ECM scaffolds may play key roles in cell recruitment. The objective of the present study was to investigate the effects of age and species of the tissue from which ECM is harvested on the chemoattractant activity of degradation products of ECM for human keratinocyte stem and progenitor cells. Adult human skin ECM, fetal human skin ECM and adult porcine skin ECM were prepared, enzymatically digested, characterized by SDS-PAGE and evaluated for in vitro chemoattractant activity for human keratinocyte progenitor and stem cells (HEKn). Degradation products of human fetal skin ECM showed greater chemoattractant activity than human adult skin ECM degradation products for the HEKn. Degradation products of porcine adult skin ECM showed greater chemoattractant activity than human adult skin ECM. The human fetal skin ECM degradation products showed the strongest chemoattractant activity for the HEKn. The findings of this study support the concept that the mechanism of ECM scaffold remodelling involves the recruitment of lineage-directed progenitor cells by scaffold degradation products, and that both the age and species of the tissue from which the ECM is harvested have an effect upon this chemoattractant potential.

Antibacterial activity within degradation products of biological scaffolds composed of extracellular matrix.

Biological scaffolds composed of extracellular matrix (ECM) have been shown to be resistant to deliberate bacterial contamination in preclinical in vivo studies. The present study evaluated the degradation products resulting from the acid digestion of ECM scaffolds for antibacterial effects against clinical strains of Staphylococcus aureus and Escherichia coli. The ECM scaffolds were derived from porcine urinary bladder (UBM-ECM) and liver (L-ECM). These biological scaffolds were digested with acid at high temperatures, fractionated using ammonium sulfate precipitation, and tested for antibacterial activity in a standardized in vitro assay. Degradation products from both UBM-ECM and L-ECM demonstrated antibacterial activity against both S. aureus and E. coli. Specific ammonium sulfate fractions that showed antimicrobial activity varied for the 2 different ECM scaffold types. The results of this study suggest that several different low-molecular-weight peptides with antibacterial activity exist within ECM and that these peptides may help explain the resistance to bacterial infection provided by such biological scaffolds.