Neuromuscular adaptations of swallowing and speech in unilateral cerebral palsy: shared and distinctive traits.

Our aims were to 1) examine the neuromuscular control of swallowing and speech in children with unilateral cerebral palsy (UCP) compared with typically developing children (TDC), 2) determine shared and separate neuromuscular underpinnings of the two functions, and 3) explore the relationship between this control and behavioral outcomes in UCP. Surface electromyography (sEMG) was used to record muscle activity from the submental and superior and inferior orbicularis oris muscles during standardized swallowing and speech tasks. The variables examined were normalized mean amplitude, time to peak amplitude, and bilateral synchrony. Swallowing and speech were evaluated using standard clinical measures. Sixteen children with UCP and 16 TDC participated (7-12 yr). Children with UCP demonstrated higher normalized mean amplitude and longer time to peak amplitude across tasks than TDC (P < 0.01; and P < 0.02) and decreased bilateral synchrony than TDC for swallows (P < 0.01). Both shared and distinctive neuromuscular patterns were observed between swallowing and speech. In UCP, higher upper lip amplitude during swallows was associated with shorter normalized mealtime durations, whereas higher submental bilateral synchrony was related to longer mealtime durations. Children with UCP demonstrate neuromuscular adaptations for swallowing and speech, which should be further evaluated for potential treatment targets. Furthermore, both shared and distinctive neuromuscular underpinnings between the two functions are documented.NEW & NOTEWORTHY Systematically studying the swallowing and speech of children with UCP is new and noteworthy. We found that they demonstrate neuromuscular adaptations for swallowing and speech compared with typically developing peers. We examined swallowing and speech using carefully designed tasks, similar in motor complexity, which allowed us to directly compare patterns. We found shared and distinctive neuromuscular patterns between swallowing and speech.

Shared and Separate Neuromuscular Underpinnings of Swallowing and Motor Speech Development in the School-Age Years.

PURPOSE: Despite co-occurrence of swallowing and speech disorders in childhood, there is limited research on shared and separate neuromuscular underpinnings of these functions. The purpose of this study was to (a) compare neuromuscular control of swallowing and speech between younger and older children and (b) determine similarities and differences in neuromuscular control of swallowing and speech. METHOD: Twenty-six typically developing children (thirteen 7- to 8-year-olds and thirteen 11- to 12-year-olds) completed this cross-sectional study. Neuromuscular control was evaluated using surface electromyography of submental muscles and superior and inferior orbicularis oris muscles during parallel tasks of swallowing and speech. Outcome measures included normalized mean amplitude, burst duration, time to peak amplitude, and bilateral synchrony, which were examined using mixed-effects models. RESULTS: For normalized mean amplitude, burst duration, and time to peak amplitude, there were significant two- and three-way interactions between muscle group, task, and age group, indicating that older and younger children demonstrated different muscle activation patterns, and these patterns varied by muscle and task. No differences were noted between groups for bilateral synchrony. For parallel tasks, children demonstrated different magnitudes of normalized mean amplitude and time to peak amplitude of speech and swallowing. However, they demonstrated a similar pattern: increases in magnitude as task complexity increased. CONCLUSIONS: Children continue to demonstrate refinement of their neuromuscular control of swallowing and speech between 7-8 and 11-12 years of age, and there are both shared and separate elements of neuromuscular control between these two vital functions. To improve generalizability of findings, future research should include longitudinal analysis of swallowing and speech development, as well as measures of central neurophysiology. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23796258.

Validating expression of beta cell maturation-associated genes in human pancreas development.

The identification of genes associated with human pancreatic beta cell maturation could stimulate a better understanding of normal human islet development and function, be informative for improving stem cell-derived islet (SC-islet) differentiation, and facilitate the sorting of more mature beta cells from a pool of differentiated cells. While several candidate factors to mark beta cell maturation have been identified, much of the data supporting these markers come from animal models or differentiated SC-islets. One such marker is Urocortin-3 (UCN3). In this study, we provide evidence that UCN3 is expressed in human fetal islets well before the acquisition of functional maturation. When SC-islets expressing significant levels of UCN3 were generated, the cells did not exhibit glucose-stimulated insulin secretion, indicating that UCN3 expression is not correlated with functional maturation in these cells. We utilized our tissue bank and SC-islet resources to test an array of other candidate maturation-associated genes, and identified CHGB, G6PC2, FAM159B, GLUT1, IAPP and ENTPD3 as markers with expression patterns that correlate developmentally with the onset of functional maturation in human beta cells. We also find that human beta cell expression of ERO1LB, HDAC9, KLF9, and ZNT8 does not change between fetal and adult stages.

Telehealth Management of Dysphagia in Adults: A Survey of Speech Language Pathologists' Experiences and Perceptions.

The goal of this study was to explore telehealth use for dysphagia management in response to COVID-19 to understand variables associated with clinician confidence and perceived effectiveness of this service delivery model and determine clinician-perceived benefits and challenges of managing dysphagia via telehealth. Speech-language pathologists (SLPs, n = 235) completed a web-based survey, providing information on demographics, telehealth use during the pandemic, and perspectives on current and future tele-management of dysphagia. Analyses included descriptive statistics to examine usage patterns; logistic regression to determine which variables were associated with telehealth use, clinician confidence, and perceived-effectiveness; and conventional content analysis to analyze responses to open-ended questions. Results revealed a sharp increase in the tele-management of dysphagia during the pandemic. Years of experience with dysphagia management (p = .031) and pre-pandemic use of telehealth (p < .001) were significantly associated with current use patterns. Working in the outpatient setting was associated with greater clinician confidence (p = .003) and perceived effectiveness (p = .007), and use of guidelines (p = .042) was also associated with greater clinician confidence. Key challenges identified included inadequate technological infrastructure, inadequate patient digital literacy, and reimbursement restrictions. Key benefits were treatment continuity, improving access to care, and time savings. The majority (67%) of respondents reported that they would use telehealth in the future. These findings demonstrate SLPs' abilities and desire to expand their practice patterns to include telehealth for dysphagia management. Therefore, clinician training and more research on best practices for assessment and treatment of dysphagia via telehealth is warranted to refine models of care for dysphagia tele-management.

Effect of AMPK activation and glucose availability on myotube LAT1 expression and BCAA utilization.

Those with insulin resistance often display increased circulating branched-chain amino acids (BCAA), which has been largely attributable to reduced BCAA catabolic capacity. Metabolic stimuli such as exercise activates AMP-activated kinase (AMPK), which promotes the metabolism of BCAA and induction/activation of BCAA catabolic enzymes. Though much attention has been paid to BCAA catabolic machinery, few studies have assessed the effect of AMPK activation on the predominant BCAA transporter, L-type amino acid transporter 1 (LAT1). This study assessed the effect of AMPK activation on LAT1 expression via common chemical AMPK activators in a cell model of skeletal muscle. C2C12 myotubes were treated with either 1 mM AICAR, 1 mM Metformin, or filter-sterilized water (control) for 24 h with either low- (5 mM) or high-glucose (25 mM) media. LAT1 and pAMPK protein content were measured via western blot. BCAA media content was measured using liquid chromatography-mass spectrometry. AICAR treatment significantly increased pAMPK and reduced LAT1 expression. Collectively, pAMPK and LAT1 displayed a significant inverse relationship independent of glucose levels. During low-glucose experiments, AICAR-treated cells had higher BCAA media content compared to other groups, and an inverse relationship between LAT1 and BCAA media content was observed, however, these effects were not consistently observed during high-glucose conditions. Further investigation with AICAR with and without concurrent LAT1 inhibition (via JPH203) also revealed reduced BCAA utilization in AICAR-treated cells regardless of LAT1 inhibition (which also independently reduced BCAA utilization). pAMPK activation via AICAR (but not Metformin) may reduce LAT1 expression and BCAA uptake in a glucose-dependent manner.

Implementation of Peer Messengers to Deliver Feedback: An Observational Study to Promote Professionalism in Nursing.

BACKGROUND: The Co-Worker Observation System (CORS) is a tool and a process to address disrespectful behavior through feedback from trained peer messengers. First used by physicians and advanced practice providers (APPs), CORS has been shown to decrease instances of unprofessional behaviors among physicians and APPs. The research team assessed the feasibility and fidelity of implementing CORS for staff nurses. METHODS: CORS was implemented at three academic medical centers using a project bundle with 10 essential implementation elements. Reports of unprofessional behavior among staff nurses that were submitted through the institution's electronic reporting system were screened through natural language processing software, coded by trained CORS coders using the Martinez taxonomy, and referred to a trained peer messenger to share the observations with the nurse. A mixed methods, observational design assessed feasibility and fidelity. RESULTS: A total of 590 reports from three sites were identified by the Center for Patient and Professional Advocacy from September 1, 2019, through August 31, 2021. Most reports included more than one problematic behavior, each of which was coded. Of the peer messages, 76.5% were successfully documented using the debriefing survey as complete, 2.2% as awaiting messenger feedback, and 0.2% as awaiting messenger assignments (total of 78.9 % considered delivered). A total of 21.1% were not shared; 4.7% of reports were intentionally not shared because the issue stemmed from a new system or policy implementation (4.0%) or because of known factors affecting the nurse (0.7%). CONCLUSION: CORS can be implemented with staff nurses efficiently when nursing infrastructure is adequate.

Genetic Engineering of Immune Evasive Stem Cell-Derived Islets.

Genome editing has the potential to revolutionize many investigative and therapeutic strategies in biology and medicine. In the field of regenerative medicine, one of the leading applications of genome engineering technology is the generation of immune evasive pluripotent stem cell-derived somatic cells for transplantation. In particular, as more functional and therapeutically relevant human pluripotent stem cell-derived islets (SCDI) are produced in many labs and studied in clinical trials, there is keen interest in studying the immunogenicity of these cells and modulating allogeneic and autoimmune immune responses for therapeutic benefit. Significant experimental work has already suggested that elimination of Human Leukocytes Antigen (HLA) expression and overexpression of immunomodulatory genes can impact survival of a variety of pluripotent stem cell-derived somatic cell types. Limited work published to date focuses on stem cell-derived islets and work in a number of labs is ongoing. Rapid progress is occurring in the genome editing of human pluripotent stem cells and their progeny focused on evading destruction by the immune system in transplantation models, and while much research is still needed, there is no doubt the combined technologies of genome editing and stem cell therapy will profoundly impact transplantation medicine in the future.

Swallowing and Motor Speech Skills in Unilateral Cerebral Palsy: Novel Findings From a Preliminary Cross-Sectional Study.

PURPOSE: Our purpose was to start examining clinical swallowing and motor speech skills of school-age children with unilateral cerebral palsy (UCP) compared to typically developing children (TDC), how these skills relate to each other, and whether they are predicted by clinical/demographic data (age, birth history, lesion type, etc.). METHOD: Seventeen children with UCP and 17 TDC (7-12 years old) participated in this cross-sectional study. Feeding/swallowing skills were evaluated using the Dysphagia Disorder Survey (DDS) and a normalized measure of mealtime efficiency (normalized mealtime duration, i.e., nMD). Motor speech was assessed via speech intelligibility and speech rate measures using the Test of Children's Speech Plus. Analyses included nonparametric bootstrapping, correlation analysis, and multiple regression. RESULTS: Children with UCP exhibited more severe (higher) DDS scores (p = .0096, Part 1; p = .0132, Part 2) and reduced speech rate than TDC (p = .0120). Furthermore, in children with UCP, total DDS scores were moderately negatively correlated with speech intelligibility (words: r = -.6162, p = .0086; sentences: r = -.60792, p = .0096). Expressive language scores were the only significant predictor of feeding and swallowing performance, and receptive language scores were the only significant predictor of motor speech skills. CONCLUSIONS: Swallowing and motor speech skills can be affected in school-age children with UCP, with wide variability of performance also noted. Preliminary cross-system interactions between swallowing, speech, and language are observed and might support the complex relationships between these domains. Further understanding these relationships in this population could have prognostic and/or therapeutic value and warrants further study.

Can electroencephalography (EEG) identify ADHD subtypes? A systematic review.

Attention Deficit/Hyperactivity Disorder (ADHD) has been associated with atypical patterns of neural activity measured by electroencephalography (EEG). However, the identification of EEG diagnostic biomarkers has been complicated by the disorder's heterogeneity. The objective of this review was to synthesize the literature investigating EEG variation in patients diagnosed with ADHD, addressing the following questions: 1) Are the diagnostic ADHD subtypes associated with different EEG characteristics? 2) Are EEG measures correlated with ADHD traits and/or symptom severity? and 3) Do classification techniques using EEG measures reveal different clinical presentations of ADHD? Outcomes highlight the potential for electrophysiological measures to provide meaningful insights into the heterogeneity of ADHD, although direct translation of EEG biomarkers for diagnostic purposes is not yet supported. Key measures that show promise for the discrimination of existing ADHD subtypes and symptomatology include: resting state and task-related modulation of alpha, beta and theta power, and the event-related N2 and P3 components. Prescriptions are discussed for future studies that may help to bridge the gap between research and clinical application.

A human pancreatic ECM hydrogel optimized for 3-D modeling of the islet microenvironment.

Extracellular matrix (ECM) plays a multitude of roles, including supporting cells through structural and biochemical interactions. ECM is damaged in the process of isolating human islets for clinical transplantation and basic research. A platform in which islets can be cultured in contact with natural pancreatic ECM is desirable to better understand and support islet health, and to recapitulate the native islet environment. Our study demonstrates the derivation of a practical and durable hydrogel from decellularized human pancreas that supports human islet survival and function. Islets embedded in this hydrogel show increased glucose- and KCl-stimulated insulin secretion, and improved mitochondrial function compared to islets cultured without pancreatic matrix. In extended culture, hydrogel co-culture significantly reduced levels of apoptosis compared to suspension culture and preserved controlled glucose-responsive function. Isolated islets displayed altered endocrine and non-endocrine cell arrangement compared to in situ islets; hydrogel preserved an islet architecture more similar to that observed in situ. RNA sequencing confirmed that gene expression differences between islets cultured in suspension and hydrogel largely fell within gene ontology terms related to extracellular signaling and adhesion. Natural pancreatic ECM improves the survival and physiology of isolated human islets.

Timing of birth and adverse pregnancy outcomes in cases of prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa. DATA SOURCES: Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022. STUDY ELIGIBILITY CRITERIA: The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth. METHODS: Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions. RESULTS: The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from <32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score <7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score <7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation. CONCLUSION: Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa.

Telehealth for Dysphagia Across the Life Span: Using Contemporary Evidence and Expertise to Guide Clinical Practice During and After COVID-19.

Purpose Our aim was to critically review recent literature on the use of telehealth for dysphagia during the COVID-19 pandemic and enhance this information in order to provide evidence- and practice-based clinical guidance during and after the pandemic. Method We conducted a rapid systematized review to identify telehealth adaptations during COVID-19, according to peer-reviewed articles published from January to August 2020. Of the 40 articles identified, 11 met the inclusion criteria. Full-text reviews were completed by three raters, followed by qualitative synthesis of the results and description of practical recommendations for the use of telehealth for dysphagia. Results Seven articles were guidelines articles, three were editorials, and one was a narrative review. One article focused on telehealth and dysphagia during COVID-19. The remaining 10 mentioned telehealth in varying degrees while focusing on dysphagia management during the pandemic. No articles discussed pediatrics in depth. The most common procedure for which telehealth was recommended was the clinical swallowing assessment (8/11), followed by therapy (7/11). Six articles characterized telehealth as a second-tier service delivery option. Only one article included brief guidance on telehealth-specific factors, such as legal safeguards, safety, privacy, infrastructure, and facilitators. Conclusions Literature published during the pandemic on telehealth for dysphagia is extremely limited and guarded in endorsing telehealth as an equivalent service delivery model. We have presented prepandemic and emerging current evidence for the safety and reliability of dysphagia telemanagement, in combination with practical guidelines to facilitate the safe adoption of telehealth during and after the pandemic.

Proteome-wide and matrisome-specific alterations during human pancreas development and maturation.

The extracellular matrix (ECM) is unique to each tissue and capable of guiding cell differentiation, migration, morphology, and function. The ECM proteome of different developmental stages has not been systematically studied in the human pancreas. In this study, we apply mass spectrometry-based quantitative proteomics strategies using N,N-dimethyl leucine isobaric tags to delineate proteome-wide and ECM-specific alterations in four age groups: fetal (18-20 weeks gestation), juvenile (5-16 years old), young adults (21-29 years old) and older adults (50-61 years old). We identify 3,523 proteins including 185 ECM proteins and quantify 117 of them. We detect previously unknown proteome and matrisome features during pancreas development and maturation. We also visualize specific ECM proteins of interest using immunofluorescent staining and investigate changes in ECM localization within islet or acinar compartments. This comprehensive proteomics analysis contributes to an improved understanding of the critical roles that ECM plays throughout human pancreas development and maturation.

Acute high-dose titanium dioxide nanoparticle exposure alters gastrointestinal homeostasis in mice.

Human exposure to a wide variety of engineered nanoparticles (NPs) is on the rise and use in common food additives increases gastrointestinal (GI) exposure. Host health is intricately linked to the GI microbiome and immune response. Perturbations in the microbiota can affect energy harvest, trigger inflammation and alter the mucosal barrier leading to various disease states such as obesity and inflammatory bowel diseases. We hypothesized that single high-dose titanium dioxide (TiO2 ) NP exposure in mice would lead to dysbiosis and stimulate mucus production and local immune populations. Juvenile mice (9-10 weeks) were gavaged with 1 g/kg TiO2 NPs and examined for changes in mucosa-associated bacteria abundance, inflammatory cytokines, mucin expression and body mass. Our data provide support that TiO2 NP ingestion alters the GI microbiota and host defenses promoting metabolic disruption and subsequently weight gain in mice.

Contralateral delay activity is not a robust marker of cognitive function in older adults at risk of mild cognitive impairment.

Contralateral delay activity (CDA) has been proposed as a pre-clinical neural marker for mild cognitive impairment (MCI). However, existing evidence is limited to one study with a small sample size (n = 24). Our aim was to extend previous work by investigating the relationship between the CDA and MCI risk in a large sample of older adults (n = 76). We used a regression approach to determine whether (and when) CDA amplitude predicted MCI risk, as indexed by the Montreal Cognitive Assessment (MoCA). CDA amplitude from ~300-500 and ~800-900 ms predicted MoCA performance. However, significant effects were only observed for specific electrodes (P5/P6 and CP3/CP4, but not PO7/PO8) and the nature of the relationship between the CDA and MoCA scores differed across time and according to set size. Bayesian regression analysis indicated partial evidence in favour of the null hypothesis (BF10 values = 4-1.18). Contrary to previous results, our findings suggest that the CDA may not a robust marker of MCI risk. More broadly, our results highlight the difficulty in identifying at-risk individuals, particularly as MCI is a heterogeneous, unstable condition. Future research should prioritise longitudinal approaches in order to track the progression of the CDA and its association with cognitive decline in later life.

Hypertension, but not body mass index, is predictive of increased pancreatic lipid content and islet dysfunction.

Pancreatic steatosis is thought to be a negative risk factor for pancreas transplant outcomes. Despite considering donor body mass index (BMI) and the visualization of intercalated fat as indicators of donor pancreas lipid content, transplant surgeons do not use a quantitative method to directly measure steatosis when deciding to transplant a pancreas. In this study, we used nondiabetic human pancreata donated for research to measure the pancreatic and islet-specific lipid content to determine which clinical markers correlate best with lipid content. Interestingly, we found that BMI and age correlate with increased pancreatic lipid content (Panc-LC) in men, but not women. Our findings further suggest that total Panc-LC correlates with an increase in islet lipid content for both men and women. We noted that pancreata donated from individuals with a history of hypertension have increased Panc-LC independent of donor BMI or sex. Moreover, we identify hypertension as a risk factor for reduced islet function after islet isolation. Together, our findings emphasize differences in pancreas graft quality related to pancreatic and islet lipid content, which may not be predicted by assessing BMI alone but may be influenced by a donor history of hypertension.

Mimicking nature-made beta cells: recent advances towards stem cell-derived islets.

PURPOSE OF REVIEW: Stem cell-derived islets are likely to be useful as a future treatment for diabetes. However, the field has been limited in the ability to generate ß-like cells with both phenotypic maturation and functional glucose-stimulated insulin secretion that is similar to primary human islets. The field must also establish a reliable method of delivering the cells to patients while promoting rapid in-vivo engraftment and function. Overcoming these barriers to ß cell differentiation and transplantation will be key to bring this therapy to the clinic. RECENT FINDINGS: The ability to generate stem cell-derived ß-like cells capable of dynamic glucose-responsive insulin secretion, as well as ß-like cells expressing key maturation genes has recently been demonstrated by several groups. Other groups have explored the potential of vascularized subcutaneous transplant sites, as well as endothelial cell co-transplant to support ß cell survival and function following transplantation. SUMMARY: The generation of stem cell-derived islets with dynamic glucose-responsive insulin secretion has brought the field closer to clinical translation, but there is still need for improving insulin content and secretory capacity, as well as understanding the factors affecting variable consistency and heterogeneity of the islet-like clusters. Other questions remain regarding how to address safety, immunogenicity and transplantation site moving forward.

Preliminary application of Structure from Motion and GIS to document decomposition and taphonomic processes.

Over the past decade, Structure from Motion (SfM) has increasingly been used as a means of digital preservation and for documenting archaeological excavations, architecture, and cultural material. However, few studies have tapped the potential of using SfM to document and analyze taphonomic processes affecting burials for forensic sciences purposes. This project utilizes SfM models to elucidate specific post-depositional events that affected a series of three human cadavers deposited at the South East Texas Applied Forensic Science Facility (STAFS). The aim of this research was to test the ability for untrained researchers to employ spatial software and photogrammetry for data collection purposes. For a series of three months a single lens reflex (SLR) camera was used to capture a series of overlapping images at periodic stages in the decomposition process of each cadaver. These images are processed through photogrammetric software that creates a 3D model that can be measured, manipulated, and viewed. This project used photogrammetric and geospatial software to map changes in decomposition and movement of the body from original deposition points. Project results indicate SfM and GIS as a useful tool for documenting decomposition and taphonomic processes. Results indicate photogrammetry is an efficient, relatively simple, and affordable tool for the documentation of decomposition.

Direct excitation of parvalbumin-positive interneurons by M1 muscarinic acetylcholine receptors: roles in cellular excitability, inhibitory transmission and cognition.

Parvalbumin-containing (PV) neurons, a major class of GABAergic interneurons, are essential circuit elements of learning networks. As levels of acetylcholine rise during active learning tasks, PV neurons become increasingly engaged in network dynamics. Conversely, impairment of either cholinergic or PV interneuron function induces learning deficits. Here, we examined PV interneurons in hippocampus (HC) and prefrontal cortex (PFC) and their modulation by muscarinic acetylcholine receptors (mAChRs). HC PV cells, visualized by crossing PV-CRE mice with Rosa26YFP mice, were anatomically identified as basket cells and PV bistratified cells in the stratum pyramidale; in stratum oriens, HC PV cells were electrophysiologically distinct from somatostatin-containing cells. With glutamatergic transmission pharmacologically blocked, mAChR activation enhanced PV cell excitability in both CA1 HC and PFC; however, CA1 HC PV cells exhibited a stronger postsynaptic depolarization than PFC PV cells. To delete M1 mAChRs genetically from PV interneurons, we created PV-M1 knockout mice by crossing PV-CRE and floxed M1 mice. The elimination of M1 mAChRs from PV cells diminished M1 mAChR immunoreactivity and muscarinic excitation of HC PV cells. Selective cholinergic activation of HC PV interneurons using Designer Receptors Exclusively Activated by Designer Drugs technology enhanced the frequency and amplitude of inhibitory synaptic currents in CA1 pyramidal cells. Finally, relative to wild-type controls, PV-M1 knockout mice exhibited impaired novel object recognition and, to a lesser extent, impaired spatial working memory, but reference memory remained intact. Therefore, the direct activation of M1 mAChRs on PV cells contributes to some forms of learning and memory.