Experience-dependent Neuroplasticity Research Articles

The role of formal schooling in the development of children's reading and arithmetic white matter networks.

Children's white matter development is driven by experience, yet it remains poorly understood how it is shaped by attending formal education. A small number of studies compared children before and after the start of formal schooling to understand this, yet they do not allow to separate maturational effects from schooling-related effects. A clever way to (quasi-)experimentally address this issue is the longitudinal school cut-off design, which compares children who are similar in age but differ in schooling (because they are born right before or after the cut-off date for school entry). We used for the first time such a longitudinal school cut-off design to experimentally investigate the effect of schooling on children's white matter networks. We compared "young" first graders (schooling group, n=34; Mage=68 months; 20 girls) and "old" preschoolers (non-schooling group, n=33; Mage=66 months; 18 girls) that were similar in age but differed in the amount of formal instruction they received. Our study revealed that changes in fractional anisotropy and mean diffusivity in five a priori selected white matter tracts during the transition from preschool to primary school were predominantly driven by age-related maturation. We did not find specific schooling effects on white matter, despite their strong presence for early reading and early arithmetic skills. The present study is the first to disentangle the effects of age-related maturation and schooling on white matter within a longitudinal cohort of 5-year-old preschoolers. RESEARCH HIGHLIGHTS: White matter tracts that have been associated with reading and arithmetic may be susceptible to experience-dependent neuroplasticity when children learn to read and calculate. This longitudinal study used the school cut-off design to isolate schooling-induced from coinciding maturational influences on children's white matter development. White matter changes during the transition from preschool to primary school are predominantly driven by age-related maturation and not by schooling effects. Strong effects of schooling on behavior were shown for early reading and early arithmetic, but not for verbal ability and spatial ability.

Physiotherapy-assisted overground exoskeleton use: mixed methods feasibility study protocol quantifying the user experience, as well as functional, neural, and muscular outcomes in children with mobility impairments.

Early phase research suggests that physiotherapy paired with use of robotic walking aids provides a novel opportunity for children with severe mobility challenges to experience active walking. The Trexo Plus is a pediatric lower limb exoskeleton mounted on a wheeled walker frame, and is adjustable to fit a child's positional and gait requirements. It guides and powers the child's leg movements in a way that is individualized to their movement potential and upright support needs, and can provide progressive challenges for walking within a physiotherapy-based motor learning treatment paradigm. This protocol outlines a single group mixed-methods study that assesses the feasibility of physiotherapy-assisted overground Trexo use in school and outpatient settings during a 6-week physiotherapy block. Children ages 3-6 years (n = 10; cerebral palsy or related disorder, Gross Motor Function Classification System level IV) will be recruited by circle of care invitations to participate. Study indicators/outcomes will focus on evaluation of: (i) clinical feasibility, safety, and acceptability of intervention; (ii) pre-post intervention motor/functional outcomes; (iii) pre-post intervention brain structure characterization and resting state brain connectivity; (iv) muscle activity characterization during Trexo-assisted gait and natural assisted gait; (v) heart rate during Trexo-assisted gait and natural assisted gait; and (vi) user experience and perceptions of physiotherapists, children, and parents. This will be the first study to investigate feasibility indicators, outcomes, and experiences of Trexo-based physiotherapy in a school and outpatient context with children who have mobility challenges. It will explore the possibility of experience-dependent neuroplasticity in the context of gait rehabilitation, as well as associated functional and muscular outcomes. Finally, the study will address important questions about clinical utility and future adoption of the device from the physiotherapists' perspective, comfort and engagement from the children's perspective, and the impressions of parents about the value of introducing this technology as an early intervention. https://clinicaltrials.gov, identifier NCT05463211.

Myogenic artifacts masquerade as neuroplasticity in the auditory frequency-following response.

The frequency-following response (FFR) is an evoked potential that provides a neural index of complex sound encoding in the brain. FFRs have been widely used to characterize speech and music processing, experience-dependent neuroplasticity (e.g., learning and musicianship), and biomarkers for hearing and language-based disorders that distort receptive communication abilities. It is widely assumed that FFRs stem from a mixture of phase-locked neurogenic activity from the brainstem and cortical structures along the hearing neuraxis. In this study, we challenge this prevailing view by demonstrating that upwards of ~50% of the FFR can originate from an unexpected myogenic source: contamination from the postauricular muscle (PAM) vestigial startle reflex. We measured PAM, transient auditory brainstem responses (ABRs), and sustained frequency-following response (FFR) potentials reflecting myogenic (PAM) and neurogenic (ABR/FFR) responses in young, normal-hearing listeners with varying degrees of musical training. We first establish that PAM artifact is present in all ears, varies with electrode proximity to the muscle, and can be experimentally manipulated by directing listeners' eye gaze toward the ear of sound stimulation. We then show this muscular noise easily confounds auditory FFRs, spuriously amplifying responses 3-4-fold with tandem PAM contraction and even explaining putative FFR enhancements observed in highly skilled musicians. Our findings expose a new and unrecognized myogenic source to the FFR that drives its large inter-subject variability and cast doubt on whether changes in the response typically attributed to neuroplasticity/pathology are solely of brain origin.

Testing PET-[11C]ABP688 as a tool to quantify glutamate release in vivo

Abstract The excitatory neurotransmitter glutamate plays a critical role in experience-dependent neuroplasticity, including addiction-related processes. To date, however, it is not possible to measure glutamate release in the living human brain. Positron emission tomography (PET) with [11C]ABP688, a selective allosteric antagonist of metabotropic type 5 glutamate (mGlu5) receptors, could offer an effective strategy. To test this proposition, we conducted a series of studies in rats using microdialysis and [11C]ABP688 microPET imaging, and in humans using PET and magnetic resonance spectroscopy (MRS). Significant calcium-dependent glutamate release was identified in the ventral striatum of awake rats (190.5 ± 34.7%, p < 0.05; n = 7) following administration of a low dose of ethanol (EtOH; 20%, 0.5 g/kg), a pharmacological challenge readily translatable to human research. Simultaneous microdialysis and microPET studies in anesthetized rats yielded concurrent increases in glutamate release (126.9 ± 5.3%, p < 0.001; n = 11) and decreases in striatal [11C]ABP688 binding (6.8 ± 9.6%, p < 0.05). These latter two effects, however, were not significantly correlated (r = 0.25, p = 0.46). In humans, a laboratory stressor yielded significant changes in self-reported mood (ps < 0.041), sympathetic system activations (ps < 0.042), and the MRS index of striatal glutamate reuptake following excitatory neurotransmission, Glx/Cr levels (p = 0.048). These effects, however, were not accompanied by significant changes in [11C]ABP688 BPND (ps > 0.21, n = 9) or correlated with each other (ps > 0.074). Together, these studies document EtOH-induced glutamate release from neurons, EtOH-induced decreases in [11C]ABP688 binding, and stress-induced changes in glutamate turnover, yet fail to provide evidence that the PET [11C]ABP688 method can be exploited to quantify moderate changes in glutamate release. The results underscore the need for highly controlled testing conditions during PET measures of mGlu5 receptors.

A neural mechanism of cognitive reserve: The case of bilingualism

Cognitive Reserve (CR) refers to the preservation of cognitive function in the face of age- or disease-related neuroanatomical decline. While bilingualism has been shown to contribute to CR, the extent to which, and what particular aspect of, second language experience contributes to CR are debated, and the underlying neural mechanism(s) unknown. Intrinsic functional connectivity reflects experience-dependent neuroplasticity that occurs across timescales ranging from minutes to decades, and may be a neural mechanism underlying CR. To test this hypothesis, we used voxel-based morphometry and resting-state functional connectivity analyses of MRI data to compare structural and functional brain integrity between monolingual and bilingual older adults, matched on cognitive performance, and across levels of second language proficiency measured as a continuous variable. Bilingualism, and degree of second language proficiency specifically, were associated with lower gray matter integrity in a hub of the default mode network – a region that is particularly vulnerable to decline in aging and dementia – but preserved intrinsic functional network organization. Bilingualism moderated the association between neuroanatomical differences and cognitive decline, such that lower gray matter integrity was associated with lower executive function in monolinguals, but not bilinguals. Intrinsic functional network integrity predicted executive function when controlling for group differences in gray matter integrity and language status. Our findings confirm that lifelong bilingualism is a CR factor, as bilingual older adults performed just as well as their monolingual peers on tasks of executive function, despite showing signs of more advanced neuroanatomical aging, and that this is a consequence of preserved intrinsic functional network organization.

Cover Image

Human Brain MappingVolume 44, Issue 6 COVER IMAGEFree Access Cover Image First published: 21 March 2023 https://doi.org/10.1002/hbm.25919AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract COVER ILLUSTRATION Graph theory analysis reveals enhanced strength centrality in the left amygdala of vocalists and pianists, which indicates a high degree of interconnectivity between the left amygdala and other brain regions. This suggests that long-term musical training has effects on experience dependent neuroplasticity in the amygdala-centered networks, which is a generic function while performing musical arts. Volume44, Issue6April 15, 2023 RelatedInformation

Cover Image

Human Brain MappingVolume 44, Issue 5 COVER IMAGEFree Access Cover Image First published: 02 March 2023 https://doi.org/10.1002/hbm.25917AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract COVER ILLUSTRATION Graph theory analysis reveals enhanced strength centrality in the left amygdala of vocalists and pianists, which indicates a high degree of interconnectivity between the left amygdala and other brain regions. This suggests that long-term musical training has effects on experiencedependent neuroplasticity in the amygdala-centered networks, which is a generic function while performing musical arts. Volume44, Issue5April 1, 2023 RelatedInformation

Dynamic effects of bilingualism on brain structure map onto general principles of experience-based neuroplasticity

Bilingualism has been linked to structural adaptations of subcortical brain regions that are important for controlling multiple languages. However, research on the location and extent of these adaptations has yielded variable patterns, especially as far as the subcortical regions are concerned. Existing literature on bilingualism-induced brain restructuring has so far largely overseen evidence from other domains showing that experience-based structural neuroplasticity often triggers non-linear adaptations which follow expansion-renormalisation trajectories. Here we use generalised additive mixed models to investigate the non-linear effects of quantified bilingual experiences on the basal ganglia and the thalamus in a sample of bilinguals with a wide range of bilingual experiences. Our results revealed that volumes of the bilateral caudate nucleus and nucleus accumbens were significantly related to bilingual experiences. Importantly, these followed a non-linear pattern, with increases followed by plateauing in the most experienced bilinguals, suggesting that experience-based volumetric increases are only necessary up to a certain level of bilingual experience. Moreover, the volumes of putamen and thalamus were positively predicted by bilingual experiences. The results offer the first direct evidence that bilingualism, similarly to other cognitively demanding skills, leads to dynamic subcortical structural adaptations which can be nonlinear, in line with expansion-renormalisation models of experience-dependent neuroplasticity.

Cover Image

Human Brain MappingVolume 44, Issue 3 COVER IMAGEFree Access Cover Image First published: 25 January 2023 https://doi.org/10.1002/hbm.25913AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract COVER ILLUSTRATION Graph theory analysis reveals enhanced strength centrality in the left amygdala of vocalists and pianists, which indicates a high degree of interconnectivity between the left amygdala and other brain regions. This suggests that long-term musical training has effects on experiencedependent neuroplasticity in the amygdala-centered networks, which is a generic function while performing musical arts. Volume44, Issue3February 15, 2023 RelatedInformation

An allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors reduces the cocaine-stimulated ERK1/2 phosphorylation in the mouse striatum

Metabotropic glutamate (mGlu) receptors are involved in the experience-dependent neuroplasticity in the mesolimbic reward circuit. A Gαi/o-coupled mGlu2 subtype is distributed presynaptically in the striatum. These autoreceptors may have a significant influence over striatal neurons in their intracellular signaling pathways in response to a psychostimulant. Here we explored the effect of pharmacological potentiation of mGlu2 receptors on cocaine-stimulated phosphorylation (activation) of extracellular signal-regulated kinases (ERK) in the mouse striatum in vivo. We found that an mGlu2 selective positive allosteric modulator (PAM) LY487379 after a systemic injection did not alter basal phosphorylation of ERK1/2 or c-Jun N-terminal kinases in the striatum. However, pretreatment with LY487379 blocked the ERK1/2 phosphorylation induced by cocaine in the two subdivisions of the striatum, i.e., the caudate putamen and nucleus accumbens. LY487379 also blocked the cocaine-induced phosphorylation of Elk-1, a transcription factor downstream to the ERK pathway. Additionally, LY487379 reduced locomotor behavioral responses to cocaine. These results demonstrate that the mGlu2 PAM LY487379 possesses the ability to attenuate the activation of the ERK1/2 pathway in striatal neurons and reduce locomotor activity in response to cocaine in vivo.

Neurosexism, Neurofeminism, and Neurocentrism: From Gendered Brains to Embodied Minds

ABSTRACT Over the course of the last decade, a strand of feminist science scholarship has come together under the rubric of “neurofeminism”. One of the driving concerns for scholars in this area is to expose and criticize what is sometimes called “neurosexism”. This is a tendency among some neuroscientists, science writers and journalists to exaggerate cognitive, emotional, and behavioural sex differences and to pin gender stereotypes on allegedly innate sex differences of brain structure and function. The standard neurofeminist response has operated largely within the framework of the nature vs. nurture problematic, emphasizing the lack of attention to the role played by experience-dependent neuroplasticity in the development of a gendered brain. I propose to reframe this debate using resources from the philosophy of mind. I argue that several issues driving this debate hinge on the more fundamental question of how the role of the brain in behaviour should be conceptualized. In this regard, I show how neurosexism assumes neurocentrism—which I explicate as the transposition of the Cartesian immaterial soul onto the material brain—as its philosophical foundation, and I develop the case against this assumption, drawing in part on the enactive approach to the philosophy and science of the mind.

Growing Brains, Nurturing Minds-Neuroscience as an Educational Tool to Support Students' Development as Life-Long Learners.

Compared to other primates, humans are late bloomers, with exceptionally long childhood and adolescence. The extensive developmental period of humans is thought to facilitate the learning processes required for the growth and maturation of the complex human brain. During the first two and a half decades of life, the human brain is a construction site, and learning processes direct its shaping through experience-dependent neuroplasticity. Formal and informal learning, which generates long-term and accessible knowledge, is mediated by neuroplasticity to create adaptive structural and functional changes in brain networks. Since experience-dependent neuroplasticity is at full force during school years, it holds a tremendous educational opportunity. In order to fulfill this developmental and learning potential, educational practices should be human-brain-friendly and "ride" the neuroplasticity wave. Neuroscience can inform educators about the natural learning mechanisms of the brain to support student learning. This review takes a neuroscientific lens to explore central concepts in education (e.g., mindset, motivation, meaning-making, and attention) and suggests two methods of using neuroscience as an educational tool: teaching students about their brain (content level) and considering the neuro-mechanisms of learning in educational design (design level).

Sleep affects higher-level categorization of speech sounds, but not frequency encoding

Sleep can increase consolidation of new knowledge and skills. It is less clear whether sleep plays a role in other aspects of experience-dependent neuroplasticity, which underlie important human capabilities such as spoken language processing. Theories of sensory learning differ in their predictions; some imply rapid learning at early sensory levels, while other propose a slow, progressive timecourse such that higher-level categorical representations guide immediate, novice learning, while lower-level sensory changes do not emerge until later stages. In this study, we investigated the role of sleep across both behavioural and physiological indices of auditory neuroplasticity. Forty healthy young human adults (23 female) who did not speak a tonal language participated in the study. They learned to categorize non-native Mandarin lexical tones using a sound-to-category training paradigm, and were then randomly assigned to a Nap or Wake condition. Polysomnographic data were recorded to quantify sleep during a 3 h afternoon nap opportunity, or equivalent period of quiet wakeful activity. Measures of behavioural performance accuracy revealed a significant improvement in learning the sound-to-category training paradigm between Nap and Wake groups. Conversely, a neural index of fine sound encoding fidelity of speech sounds known as the frequency-following response (FFR) suggested no change due to sleep, and a null model was supported, using Bayesian statistics. Together, these results support theories that propose a slow, progressive and hierarchical timecourse for sensory learning. Sleep's effect may play the biggest role in the higher-level learning, although contributions to more protracted processes of plasticity that exceed the study duration cannot be ruled out.

Enhanced biological motion perception in deaf native signers

We conducted two studies to test how deaf signed language users perceive biological motions. We created 18 Biological Motion point-light displays (PLDs) depicting everyday human actions, and 18 Scrambled control PLDs. First, we conducted an online behavioral rating survey, in which deaf and hearing raters identified the biological motion PLDs and rated how easy it was for them to identify the actions. Then, we conducted an EEG study in which Deaf Signers and Hearing Non-Signers watched both the Biological Motion PLDs and the Scrambled PLDs, and we computed the time-frequency responses within the theta, alpha, and beta EEG rhythms. From the behavioral rating task, we show that the deaf raters reported significantly less effort required for identifying the Biological motion PLDs, across all stimuli. The EEG results showed that the Deaf Signers showed theta, mu, and beta differentiation between Scrambled and Biological PLDs earlier and more consistently than Hearing Non-Signers. We conclude that native ASL users exhibit experience-dependent neuroplasticity in the domain of biological human motion perception.

Commentary on "Intensive Bimanual Intervention for Children Who Have Undergone Hemispherectomy: A Pilot Study".

“How should I apply this information?” Sensorimotor deficits that result from hemispherectomy are more severe and debilitating than other forms of hemiplegia. For families with a child who requires this surgical approach and the clinicians who support them during their postoperative rehabilitation, little information is available regarding motor changes in response to specific interventions. This preliminary work offers hope. Regardless of the subject's interhemispheric lateralization, type of hemiplegia, or length of time from surgery, clinically meaningful changes in bimanual function were reported with Hand-Arm Bimanual Intensive Training (HABIT). Given this approach received a “green-light” rating by Novak et al1 in a 2019 systematic review and it is grounded in key principles associated with experience-dependent neuroplasticity, this finding is not surprising. These key principles are focused on: task-specific practice, goal-directed tasks and activities, high-intensity doses of meaningful practice, and self-generated, active movement. From a family's perspective, HABIT represents an escape from “appointment fatigue” and an opportunity to intensively practice real-life activities. “Our daughter became more aware and intentional about using her affected side, and ... activities carried over to home!” “What should I be mindful of when applying this information?” Ninety hours of intervention within a 2-week period requires a high level of commitment from families, children, clinicians, health care organizations that employ clinicians, and third-party payers. Cost-effectiveness analysis is not considered nor are sustainable funding mechanisms discussed. For therapists providing intervention in school-based settings, this intensity of service and the one-on-one support it requires is not feasible; for those in outpatient settings, the time required for organizing and implementing HABIT, the materials needed to engage children across a broad range of ages for 6 hours of daily therapy, and the limited reimbursement options for therapists' one-on-one involvement require a high level of creativity and pose unique challenges. Future research should explore family perspectives, cost-effectiveness, and dose-response parameters that might further individualize the length of necessary intervention. Sandra L. Willett, PT, PhD, PCS Emily Drew, PT, PCS Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska Jennifer Dibbern Parent, Omaha, Nebraska

Experience, but not age, is associated with volumetric mushroom body expansion in solitary alkali bees.

In social insects, changes in behavior are often accompanied by structural changes in the brain. This neuroplasticity may come with experience (experience-dependent) or age (experience-expectant). Yet, the evolutionary relationship between neuroplasticity and sociality is unclear, because we know little about neuroplasticity in the solitary relatives of social species. We used confocal microscopy to measure brain changes in response to age and experience in a solitary halictid bee (Nomia melanderi). First, we compared the volume of individual brain regions among newly emerged females, laboratory females deprived of reproductive and foraging experience, and free-flying, nesting females. Experience, but not age, led to significant expansion of the mushroom bodies - higher-order processing centers associated with learning and memory. Next, we investigated how social experience influences neuroplasticity by comparing the brains of females kept in the laboratory either alone or paired with another female. Paired females had significantly larger olfactory regions of the mushroom bodies. Together, these experimental results indicate that experience-dependent neuroplasticity is common to both solitary and social taxa, whereas experience-expectant neuroplasticity may be an adaptation to life in a social colony. Further, neuroplasticity in response to social chemical signals may have facilitated the evolution of sociality.

Relationship between interhemispheric inhibition and bimanual coordination: absence of instrument specificity on motor performance in professional musicians.

Functional reorganization in a musician's brain has long been considered strong evidence of experience-dependent neuroplasticity. Highly coordinated bimanual movements require abundant communication between bilateral hemispheres. Interhemispheric inhibition (IHI) is the communication between bilateral primary motor cortices, and there is beginning evidence to suggest that IHI is modified according to instrument type, possibly due to instrument-dependent motor training. However, it is unknown whether IHI adaptations are associated with non-musical bimanual tasks that resemble specific musical instruments. Therefore, we aimed to investigate the relationship between IHI and bimanual coordination in keyboard players compared with string players. Bimanual coordination was measured by a force tracking task, categorized as symmetric and asymmetric conditions. Ipsilateral silent period (iSP) was obtained using transcranial magnetic stimulation to index IHI in both left (L) and right (R) hemispheres. Canonical correlation analysis was performed to identify linear relationships between the IHI and bimanual coordination outcomes. There was no difference in bimanual coordination outcomes between keyboard and string players. Increased iSP from the L to R hemisphere was found in string players compared to keyboard players. There appeared to be different instrument-dependent relationships between IHI and bimanual coordination, regardless of symmetric or asymmetric task. Laboratory motor assessments resembling specific features of musical instruments (symmetric vs. asymmetric hand use) did not distinctly characterize bimanual motor skills between keyboard and string players. The relationships between IHI and bimanual coordination in these two instrument types were independent of task condition. Instrument-dependent neuroplasticity may be evident only within the context of musical instrument playing.

Serotonin and early life stress interact to shape brain architecture and anxious avoidant behavior - a TPH2 imaging genetics approach.

Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance. The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.

Defining the relationship between maternal care behavior and sensory development in Wistar rats: Auditory periphery development, eye opening and brain gene expression

Defining the relationship between maternal care, sensory development and brain gene expression in neonates is important to understand the impact of environmental challenges during sensitive periods in early life. In this study, we used a selection approach to test the hypothesis that variation in maternal licking and grooming (LG) during the first week of life influences sensory development in Wistar rat pups. We tracked the onset of the auditory brainstem response (ABR), the timing of eye opening (EO), middle ear development with micro-CT X-ray tomography, and used qRT-PCR to monitor changes in gene expression of the hypoxia-sensitive pathway and neurotrophin signaling in pups reared by low-LG or high-LG dams. The results show the first evidence that the transcription of genes involved in the hypoxia-sensitive pathway and neurotrophin signaling is regulated during separate sensitive periods that occur before and after hearing onset, respectively. Although the timing of ABR onset, EO, and the relative mRNA levels of genes involved in the hypoxia-sensitive pathway did not differ between pups from different LG groups, we found statistically significant increases in the relative mRNA levels of four genes involved in neurotrophin signaling in auditory brain regions from pups of different LG backgrounds. These results suggest that sensitivity to hypoxic challenge might be widespread in the auditory system of neonate rats before hearing onset, and that maternal LG may affect the transcription of genes involved in experience-dependent neuroplasticity.

MGlu5 receptor availability in youth at risk for addictions: effects of vulnerability traits and cannabis use

The excitatory neurotransmitter glutamate has been implicated in experience-dependent neuroplasticity and drug-seeking behaviors. Type 5 metabotropic glutamate (mGlu5) receptors might be particularly important. They are critically involved in synaptic plasticity and their availability has been reported to be lower in people with alcohol, tobacco, and cocaine use disorders. Since these reductions could reflect effects of drug use or pre-existing traits, we used positron emission tomography to measure mGlu5 receptor availability in young adults at elevated risk for addictions. Fifty-nine participants (age 18.5 ± 0.6) were recruited from a longitudinal study that has followed them since birth. Based on externalizing traits that predict future substance use problems, half were at low risk, half were at high risk. Cannabis use histories varied markedly and participants were divided into three subgroups: zero, low, and high use. Compared to low risk volunteers, those at elevated risk had lower [11C]ABP688 binding potential (BPND) values in the striatum, amygdala, insula, and orbitofrontal cortex (OFC). Cannabis use by risk group interactions were observed in the striatum and OFC. In these regions, low [11C]ABP688 BPND values were only seen in the high risk group that used high quantities of cannabis. When these high risk, high cannabis use individuals were compared to all other participants, [11C]ABP688 BPND values were lower in the striatum, OFC, and insula. Together, these results provide evidence that mGlu5 receptor availability is low in youth at elevated risk for addictions, particularly those who frequently use cannabis.