April 21st, 2021
Our Research Forums feature new results, ideas, and projects from our members’ labs. This edition will feature the TACC trainees, as they present their research projects to the TACC community.
Our next TACC Research Forum will feature four TACC student members:
Speaker 1: Arjun. A. Bhaskaran, PhD
Title: “Disrupted dendritic filtering contributes to hyperexcitability in the cerebellum of Fragile X syndrome.”
Abstract: Fragile X syndrome (FXS) is the most common single gene cause of inherited intellectual disability and autism. The disease typically occurs because of the loss of expression of the Fragile X Mental Retardation Protein (FMRP), which causes hyperexcitability at the cellular and circuit level of the CNS. Here we show that the loss of FMRP causes defects in glutamatergic signaling in cerebellar molecular layer interneurons (MLIs) of Fmr1- KO mouse model of FXS. An excitatory parallel fiber stimulation caused significantly larger but briefer excitatory postsynaptic potentials (EPSPs) in Fmr1-KO MLIs. We found that GABAergic currents are greater in Fmr1-KO MLIs and introduction of bicuculline, a GABA inhibitor in the bath has eliminated the variation in EPSP duration but not the peak amplitude in Fmr1-KO neurons. Furthermore, we demonstrated that the increased peak amplitude in Fmr1-KO MLIs is largely contributed by TEA sensitive delayed rectifier potassium currents (Kdr). Reintroduction of an N-terminal fragment of FMRP (N-FMRP) reduced the EPSP peak amplitude in Fmr1-KO MLIs through direct interaction with TEA sensitive potassium channels. Furthermore, Fmr-1KO MLIs showed increased spontaneous and intrinsic action potential (AP) firing rate as well as an increased AP firing in response to parallel fiber stimulation. Interestingly, application of N-FMRP also reduced the hyperexcitability in Fmr1-KO neurons. Overall, this study reveals a novel defect in hyperexcitability and develops additional insight into the function of the N-FMRP in regulating neuronal excitability.
Bio: Dr. Arjun A. Bhaskaran completed his PhD degree in Neuroscience from the University of Bordeaux under the supervision of Dr. Andreas Frick. He later joined the Bowie Lab of McGill University as a postdoctoral researcher, under the mentorship of Professor Dr. Derek Bowie. His main area of research interest is that of the cellular and circuit deficits in Fragile X syndrome. Currently, at the Bowie Lab, Dr. Bhaskaran focuses on hyperexcitability and altered dendritic filtering in the FXS cerebellum.
Speaker 2: Athanasios (Tommy) Markopoulos, BSc
Title: “Behavioral Phenotyping Three Transgenic Mouse Models of Autism Spectrum Disorder”
Abstract: Autism Spectrum Disorder encompasses a variety of heterogeneous disorders with fundamental impairments in social behavior. Although the etiology underlying many ASD diagnoses are poorly understood, 5-10% are associated with monogenic syndromes, including single mutations to genes such as: Fragile X Mental Retardation 1 (Fmr1), Tuberous Sclerosis Complex 2 (Tsc2), and SH3 And Multiple Ankyrin Repeat Domains 3 (Shank3). These characterized disorders have allowed the development of transgenic mouse lines that recapitulate the genetic syndromes seen in humans. Despite these advancements, there is much inconsistency in the scientific literature about the behavioral phenotypes of these mouse models, which limits their translational potential. This inconsistency might be due to the sensitivity of rodents to testing environment, which is strongly variable across different laboratories. In the present study, we have employed a battery of behavioral assays (Direct Social Interaction Test, Three Chambers Test, Elevated Plus-Maze Test, Light-Dark Box Test, Open Field Test) to three transgenic mouse models of ASD (Fmr1 KO, Tsc2 KO, Shank3 KO) in order to characterize social behavior, anxiety-related behavior, and locomotion in a constant laboratory setting. We have identified fundamental, but varying levels of anti-social behavior which is present in all three models of ASD. As well, we have found that while the Tsc2 KO mice display more anxiety-related behavior compared to wild type littermates, Fmr1 and Shank3 mice display less anxiety-related behavior. These results provide further evidence of the validity of these transgenic mouse lines as preclinical models of ASD and contribute to better understanding their behavioral phenotypes.
Bio: Athanasios (Tommy) Markopoulos is an MSc student in the Integrated Program in Neuroscience at McGill University under the supervision of Dr. Gabriella Gobbi. He is currently using transgenic mouse models of autism spectrum disorder to identify fundamental impairments in neurotransmission that underlie the complex behavioral phenotypes of the disorder using behavioral assays, in vivo electrophysiology, and optogenetics.
Speaker 3: Jeffrey McCrossin, MSc, MSW
Title: “A Case Study Examining the Role of Peer Support When Navigating Services for Children with Neurodisabilities”
Abstract: Families of children with Autism Spectrum Disorder and other neurodisabilities face challenges navigating a confusing web of siloed services across health, social, and education sectors offered by governmental and community-based programs or organizations. Navigation supports exist to guide families and bridge siloes to increase visibility, uptake, and accessibility of services. However, ‘navigation’ is not uniformly defined. How it operates is not well understood and varies by context. The objective of this study is to describe an innovative navigation network in British Columbia that enables caregivers of children with disabilities to obtain support from their peers. Using a case study approach, a parent-to-parent navigation network will be described in detail. Thematic analysis of interviews with caregivers provides a rich qualitative description of relationships and processes. Peer support is a unique form of navigation that enhances access to services through shared lived experience. By leveraging self-reflection and expression of emotion, peers provide empathy and bridge relationships between caregivers and service providers. Peers contribute to increasing clarity around caregiver needs, allowing service providers to better tailor the support offered to families. Findings suggest that peer support does not replace professional support but instead plays a complementary role in helping caregivers feel understood and access services that are meaningful to them. Peers can benefit from developing navigation skills, however their role demands significant self-reflection and emotional investment. An additional layer of support to care for peer supporters may contribute to the sustainability of peer support networks.
Bio: Jeffrey McCrossin is a PhD candidate at McGill University’s School of Social Work. His research focuses on services and supports that foster resilience in families of children with neurodisabilities. He is also currently working at a private practice as a social worker, couple and family therapist, and psychotherapist.
Speaker 4: Myriam Beauchamp, PhD
Title: “Does bilingualism influence the language and narrative abilities of school-aged children with ASD?”
Abstract: Narratives are an important part of language abilities, serve a vital communicative function (Norbury et al., 2013) and have been linked to academic achievement (O’Neill et al., 2004). Children with autism often present difficulties with narrative skills, which may stem from difficulties in the language and social domains (Baixauli et al., 2016). While overall, bilingual children with autism can develop language abilities similar to those of their monolingual peers and may also present stronger social skills (Hambly & Fombonne, 2012), little is known about their narrative abilities. This study aims to examine the similarities and differences that exist in the narratives abilities of bilingual and monolingual children with autism. We also aim to examine to whether potential improvements in the social skills of bilingual children with autism could also benefit their narrative abilities. To answer those questions, ANCOVAs will be completed to compare the scores related to overall narrative abilities and to structural language abilities of 40 bilingual and 48 monolingual children with autism, aged 10 to 11 years. Additionally, a set of regression analyses will be completed to examine the relationship between scores from the different narrative measures and both social skills, and pragmatic language skills. The structures of the regressions will be examined to determine whether the strengths of the associations are significantly different between the two groups. Findings from this study will inform clinicians regarding the link between narrative and social skills, and about expectations when assessing bilingual children with autism. They may also inform intervention practices.
Bio: Dr. Myriam Beauchamp’s research examines bilingualism in children with and without autism. She is also interested in advocating for equitable access to services and supports for minority-language speakers. Dr. Beauchamp has been a practicing Speech-Language Pathologist for almost 10 years. She obtained her Ph.D. from Université de Montréal in June 2020 and is currently a postdoctoral researcher in Dr. Mayada Elsabbagh’s laboratory at McGill University.