Quick Project Snapshot

Utilising Touchscreen technology for preclinical modeling of attention in autism spectrum disorder

Autism is a complex spectrum of disorders characterized by core behavioural deficits in social interaction, communication, and behavioural flexibility. Autism spectrum disorder (ASD) frequently presents with additional cognitive symptoms, including attentional deficits and perceptual processing deficits. Current estimates of comorbidity of ASD and attention deficit hyperactivity disorder (ADHD) range from 41–78%. Preclinical animal models are important tools for studying the behavioural domains and biological underpinnings of autism, and potential treatment targets.  Many gene mutations that contribute to ASD have recently been identified.  These findings have lead to the development of genetic mouse models which display behavioural phenotypes mimicking ASD traits. This project takes advantage of a mouse model expressing a gene mutation coding for the Neuroligin-3 (NL3) synaptic protein identified in ASD patients. We have shown that NL3 mice show impairments in social interaction, a key criteria for validating mouse models of ASD, but other aspects of their cognitive phenotype, including attentional performance and behavioural flexibility, are not well characterised.   This project will investigate attentional abilities and behavioural flexibility of NL3 mice and their WT littermates using a novel touchscreen testing apparatus. Mice will be trained in a step-wise process to touch a computer screen for a reward. Through increasing the complexity of stimuli on the screen mice will then be assessed for visual discrimination, reversal learning, and attention. Utilising touchscreen technology may not only uncover new phenotypes in NL3 mice, but will allow us to investigate brain changes that underlie attention and behavioural flexibility. This will inform the future development of treatments for attentional deficits and impairments in behavioural flexibility in brain disorders such as ASD.

 

  1. McOmish CE, Burrows EL, Hannan AJ. Identifying novel interventional strategies for psychiatric disorders: integrating genomics, 'enviromics' and gene-environment interactions in valid preclinical models. Br J Pharmacol. 2014 May 21. 
  2. Burrows EL, Hannan AJ. Decanalization mediating gene-environment interactions  in schizophrenia and other psychiatric disorders with neurodevelopmental etiology. Front Behav Neurosci. 2013 Nov 13;7:157. 
  3. Burrows EL, Hannan AJ. Characterizing social behavior in genetically targeted  mouse models of brain disorders. Methods Mol Biol. 2013;1017:95-104. 
  4. McOmish CE, Burrows E, Howard M, Scarr E, Kim D, Shin HS, Dean B, van den Buuse M, Hannan AJ. Phospholipase C-beta1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. Mol Psychiatry. 2008 Jul;13(7):661-72. 
  5. McOmish CE, Burrows EL, Howard M, Hannan AJ. PLC-beta1 knockout mice as a model of disrupted cortical development and plasticity: behavioral endophenotypes and dysregulation of RGS4 gene expression. Hippocampus. 2008;18(8):824-34.

Epigenetics and Neural Plasticity Laboratory

The Neural Plasticity Laboratory investigates gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain, using a variety of experimental approaches.  This includes research using a model of Huntington’s disease (HD), a tandem repeat disorder, where we are following up our discoveries regarding the beneficial effects of environmental enrichment (enhanced cognitive stimulation and physical activity) and exercise, as well as depression and dementia-like symptoms associated with abnormalities of brain plasticity.  Furthermore, we recently discovered that chronic stress can accelerate onset of HD, and are investigating these neurotoxic effects of stress in HD and other brain disorders.

Many neurological and psychiatric disorders have their origins in abnormal maturation of the brain, including the billions of neurons exquisitely connected by trillions of synapses. We are also investigating how genetic and environmental factors combine to cause specific disorders of brain development and cognition, including schizophrenia and autism spectrum disorders (ASD).  We are interested in the mechanisms whereby specific genes regulate maturation of the brain and are dynamically regulated by interaction with the environment in conditions like ASD and schizophrenia. 

Our research links data at behavioural and cognitive levels to underlying cellular and molecular mechanisms.  We use a variety of behavioural tools, including automated touchscreen testing of cognition and high-throughput data analysis of vocalization and communication, that are directly translatable to clinical tests.  We are establishing the extent to which experience-dependent plasticity, including adult neurogenesis and synaptic plasticity, can modulate these behavioural and cognitive endophenotypes, in models with targeted genome editing.  This cellular level of understanding is linked, in turn, to molecular mechanisms, including epigenetics, transcriptomics and proteomics.

Based on this research, and the identification of key target molecules, we are also exploring the concept of ‘enviromimetics’, therapeutics that mimic or enhance the beneficial effects of cognitive stimulation and physical exercise.  One goal is to develop such therapeutic agents to help reduce the personal and societal burdens of devastating brain disorders such as schizophrenia, HD and dementia.

All Projects by this Lab

Investigation of paternal influence on offspring mental healthUtilising Touchscreen technology for preclinical modeling of attention in autism spectrum disorderInvestigating social communication in the Neuroligin 3 mouse model of AutismInvestigating the inherited paternal influence on offspring cognition and behaviourExperience-dependent plasticity modulating cognitive deficits in schizophreniaGene-environment interactions modulating dementia and depression in a tandem repeat disorder

Behavioural Neuroscience

The Division of Behavioural Neuroscience focuses on the use and development of models that reflect aspects of human disorders such as addiction, anxiety, depression, schizophrenia, autism and neurodegenerative conditions such as Huntington’s disease. The Cognitive Neuroscience group additionally studies cognitive disorders caused by diseases such as stroke (cerebrovascular disease), Alzheimer's disease and other dementias from a clinical perspective.

All Labs that operate in this Division

Addiction Neuroscience LaboratoryClinical Cognitive Neuroscience LaboratoryDevelopmental Psychobiology LaboratoryEpigenetics and Neural Plasticity LaboratoryGenes Environment and Behaviour LaboratoryInhalant Addiction LaboratoryMidbrain Dopamine Plasticity LaboratorySynapse Biology and Cognition LaboratoryVascular Neurodegeneration Research Laboratory