Linking muscarinic receptor activation to UPS-mediated object memory destabilization: Implications for long-term memory modification and storage.

Consolidated memories can become destabilized during reactivation, resulting in a transient state of instability, a process that has been hypothesized to underlie long-term memory updating. Consistent with this notion, relatively remote memories, which are resistant to standard destabilization procedures, are reliably destabilized when novel information (i.e., the opportunity for memory updating) is present during reactivation. We have also shown that cholinergic muscarinic receptor (mAChR) activation can similarly destabilize consolidated object memories. Synaptic protein degradation via the ubiquitin proteasome system (UPS) has previously been linked to destabilization of fear and object-location memories. Given the role of calcium in regulating proteasome activity, we hypothesized that activation of cholinergic receptors, specifically M1 mAChRs, stimulates the UPS via inositol triphosphate receptor (IP3R)-mediated release of intracellular calcium stores to facilitate object memory destabilization. We present converging evidence for this hypothesis, which we tested using a modified spontaneous object recognition task for rats and microinfusions into perirhinal cortex (PRh), a brain region strongly implicated in object memory. We extend our previous findings by demonstrating that M1 mAChRs are necessary for novelty-induced object memory destabilization. We also show that proteasome inhibition or IP3R antagonism in PRh prevents object memory destabilization induced by novelty or M1 mAChR stimulation. These results establish an intracellular pathway linking M1 receptors, IP3Rs, and UPS activity to object memory destabilization and suggest a previously unacknowledged role for cholinergic signaling in long-term memory modification and storage.

Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine.

OBJECTIVE: To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). STUDY DESIGN: A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. RESULTS: A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. CONCLUSIONS: Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.

Cholinergic manipulations bidirectionally regulate object memory destabilization.

Consolidated memories can become destabilized and open to modification upon retrieval. Destabilization is most reliably prompted when novel information is present during memory reactivation. We hypothesized that the neurotransmitter acetylcholine (ACh) plays an important role in novelty-induced memory destabilization because of its established involvement in new learning. Accordingly, we investigated the effects of cholinergic manipulations in rats using an object recognition paradigm that requires reactivation novelty to destabilize object memories. The muscarinic receptor antagonist scopolamine, systemically or infused directly into the perirhinal cortex, blocked this novelty-induced memory destabilization. Conversely, systemic oxotremorine or carbachol, muscarinic receptor agonists, administered systemically or intraperirhinally, respectively, mimicked the destabilizing effect of novel information during reactivation. These bidirectional effects suggest a crucial influence of ACh on memory destabilization and the updating functions of reconsolidation. This is a hitherto unappreciated mnemonic role for ACh with implications for its potential involvement in cognitive flexibility and the dynamic process of long-term memory storage.

Measuring Shear Wave Velocity in Adult Skeletal Muscle with Ultrasound 2-D Shear Wave Elastography: A Scoping Review.

Ultrasound 2-D shear wave elastography (US 2D-SWE) is a non-invasive, cost-effective tool for quantifying tissue stiffness. Amidst growing interest in US 2D-SWE for musculoskeletal research, it has been recommended that shear wave velocity (SWV) should be reported instead of elastic moduli to avoid introducing unwanted error into the data. This scoping review examined the evolving use of US 2D-SWE to measure SWV in skeletal muscle and identified strengths and weaknesses to guide future research. We searched electronic databases and key review reference lists to identify articles published between January 2000 and May 2021. Two reviewers assessed the eligibility of records during title/abstract and full-text screening, and one reviewer extracted and coded the data. Sixty-six studies met the eligibility criteria, of which 58 were published in 2017 or later. We found a striking lack of consensus regarding the effects of age and sex on skeletal muscle SWV, and widely variable reliability values. Substantial differences in methodology between studies suggest a pressing need for developing standardized, validated scanning protocols. This scoping review illustrates the breadth of application for US 2D-SWE in musculoskeletal research, and the data synthesis exposed several notable inconsistencies and gaps in current literature that warrant consideration in future studies.

Game-Based Learning in Neuroscience: Key Terminology, Literature Survey, and How To Guide to Create a Serious Game.

Game-based learning (GBL) has emerged as a promising approach to engage students and promote deep learning in a variety of educational settings. Neurology and neuroscience are complex fields that require an understanding of intricate neural structures and their functional roles. GBL can support the acquisition and application of such knowledge. In this article, we give an overview of the current state of GBL in neuroscience education. First, we review the language of gaming, establishing conceptual definitions for game elements, gamification, serious games, and GBL. Second, we discuss a literature review of games in the educational literature for adult learners involved in neuroscience. Third, we review available games intended for neuroscience education. Finally, we share tips for educators interested in developing their own educational games. By leveraging the unique features of games, including interactivity, feedback, and immersive experiences, educators and learners can engage with complex neuroscience concepts in a fun, engaging, and effective way.

Maternal Postsecondary Education Associated With Improved Cerebellar Growth After Preterm Birth.

The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years.