PRECLINICAL COMMITTEE SATELLITE MEETING OF T21RS INTERNATIONAL CONFERENCE
Understanding and using models to learn about Down Syndrome

 06/08/2022
 13:00h - 17:00h
Salon B
Members: 30 USD /  Non-members: 60 USD

Progress in research into Down syndrome, across many areas, depends on model systems, cellular, organoid, whole organism. Each system has its own advantages and disadvantages, and key technical aspects in usage. Findings in all model systems must be validated in human studies, but this can be extremely challenging, for example in the area of cognition. Here we look at animal models, human cellular, organoid, tissue models, and we ask the experts in each area to tell us about progress and pros and cons. We look at cognition across many modalities, and we finish a wide-ranging discussion of how well our models fit our needs. This meeting is designed to be informative and highly discursive, and an opportunity to learn, ask questions and make comments.

Scientific Program

PRESENTATIONS (30 mins, 10 mins each)
Chairs: Eugene Yu (USA)/Elizabeth Fisher (UK)
New studies on rodent models and guidelines for reporting animal research
Yann Herault (France), Roger Reeves (USA), Randall Roper (USA)

DISCUSSION (15 mins)
Chair: Tarik Haydar (USA)
Advantages/disadvantages/key points about different models for new users/what are we still missing?
Tarik Haydar (USA), Yann Herault (France), Roger Reeves (USA), Randall Roper (USA), Eugene Yu (USA), Elizabeth Fisher (UK)

Rodents are indispensable model organisms for Down syndrome research, so far largely responsible for revealing the majority of mechanistic mysteries associated with this genomic condition. In this session, a number of the leading investigators will offer their most recent updates on modeling and analysis of Down syndrome in mice and rats, building upon the history and setting the direction for the future.

Progress in research into Down syndrome depends on model systems and this session will focus on different human tissue and cells that capture key aspects of human biology that may not be reproduced in animal models. Human models that will be discussed include post-mortem tissue, cell lines and induced pluripotent stem cells and their derivatives. Anita Bhattacharyya will describe the strengths and weaknesses of each model and provide an overview of best practices to ensure rigor and reproducibility in studying the consequences of trisomy 21 with different human tissues and cells. The session will include brief talks by Joe Lee (USA), Peng Jiang (USA), and Marie Claude Potier (France) in which they will share their experiences and research progress using different human cells and tissue to investigate cellular and molecular aspects of Down syndrome related features, including altered cortical development and early Alzheimer’s disease. A general conversation will follow, led by Hiruy Meharena (USA), to discuss the availability of tissue and cells and highlight experimental challenges to modeling neural development and aging in Down syndrome.

In this session we will discuss whether animal models are good for modelling cognition. We will also reflect on the translational power of cognitive function in animal models of Down syndrome including species-dependent challenges. The specific questions will be: what can we model in mouse, fish or rat? Will the results apply to humans? What test has best translational potential? How to identify behaviorally relevant signatures: experimental design of behavior-omic experiments?

Chair: Mara Dierssen
Center for Genomic Regulation, Spain

Mara Dierssen (Spain): Overview. Cognitive function in animal models of Down syndrome. Where do we stand and where do we go.

DATA BLITZ
Pishan Chang (UK): Abnormal neural oscillations and synchrony in Down syndrome
Javier Zorrilla de San Martin (France):The prefrontal cortex and its electrical readouts during rodent’s cognition
Álvaro Fernández (Spain): New techniques for cognitive interrogation: opto- and chemogenetics
Tomer Illouz (Israel): Unraveling cognitive traits in mouse models using unbiased strategy classification methods

DISCUSSION
Chair: Mara Dierssen
Center for Genomic Regulation, Spain

The difficulties of moving between humans and model systems: Bill Mobley (USA), Yann Herault (France), Javier Zorrilla de San Martin (France), Randall Roper (USA), Álvaro Fernández (Spain), Pishan Chang (UK), Tomer Illouz (Israel)

Experts and young investigators will think and discuss about sross-species differences in cognitive testing; electrophysiology; omics. Humanizing or not: challenges and advantages. Neuronal circuits and oscillation-generating systems underlying the EEG: translational power; Behavioural-EEG phenotyping; pharmaco-dynamic biomarker for specific pharmacological activities; advanced rodent EEG analysis: software platforms and increased computational power

A small panel of experts will discuss the major question of working with models (mouse/human/rat/cellular/etc.), i.e. how well they recapitulate the human features of Down syndrome, including variation and ageing and environmental effects. These features are possibly most difficult to model for cognitive/behavioral traits. We will also discuss what is needed for the future of DS research with models.

Chair: William Mobley
University of California San Diego, La Jolla, CA
T21 RS President

Registration

Members: 30 USD /  Non-members: 60 USD