Research – Molecular and Behavioral Neuroscience

Our Research


Introduction

The main focus of research is in molecular mechanisms that are involved in shaping mammalian behavior, and that are dysregulated in brain and mental disorders. Research in the past decade has led to a new model of how lifetime experience or environmental factors may lead to progression of brain disorders. This new model stipulates that epigenetic mechanisms are responsible for encoding long term changes in human behavior after trauma or environmental factors. Epigenetics (latin for “above genetics”) refers to functional changes in DNA modification, structure, or packaging that do not involve changes in the DNA sequence. For example, DNA may be chemically modified by methylation at cytosine-guanine dinucleotides. In addition, the histone proteins which bind DNA may be methlyated, phosphorylated, acetylated, or ubiquinated. All of these modifications have long term effects on gene expression and DNA organization within the nucleus. Of importance, all of these regulatory mechanisms may be changed or dysregulated in neurons in the brain after traumatic events or may be influenced by our environment, including the food we eat. In original studies, we determined that specific genomic regions that are important for the psychological and physiological response to stress undergo significant changes in their methylation pattern in the brain after chronic stress in mice. Of particular importance, only mice that displayed depression-like behavior after social defeat displayed the changes in methylation patterns, and anti-depressant treatment could reverse methylation patterns. This research, together with many other recent studies from several independent laboratories, suggest that epigenetic changes in the brain may be responsible for mental and brain disorders. Many of our current research projects aim to understand the exact mechanisms of how epigenetics may influence behavior and what epigenetic changes are seen in the brains of humans with brain disorders. 

 

Current Research

Focus #1: To determine the molecular changes in the brain that are responsible for autism spectrum disorders

Autism spectrum disorders is a rapidly increasing phenomena, and is defined by the presence of three core symptoms: 1.) lack sociability 2.) problems in communication 3.) stereotypic behaviors. Our research aims to understand the molecular mechanisms in the brain that are responsible for these behaviors. We do this by combining molecular studies of post mortem brain samples of individuals with autism disorder with rodent models of autism disorders. In our current studies, we are using high throughput genomic approaches to determine changes in DNA methylation and microRNAs in the brain samples of human individuals with autism. These high throughput studies are followed by in vitro functional assays to determine the functional significance of our findings in the human individuals. This work has already revealed interesting insights into molecular differences in the autistic brain that may underly their behaviors. In seperate research, we study the behavior and molecular profile of several different mouse models of autism. These mouse models are created by mutating key genes that are known to be causative for autism spectrum disorders in humans. By profiling the behavioral profile of several models and discovering molecular changes in these mouse models, we aim to more fully understand the molecular changes that are causative of autistic behavior.

 

Focus #2: To determine the role of epigenetic factors in brain function and brain disorders

As explained above, epigenetic control of gene expression is a major factor that underlies brain function and mamallian behavior. This is particularly evident from the fact that mutations in many epigenetic factors that bind DNA can cause mental and/or neurodevelopmental disorders. Therefore, aim to determine the exact molecular pathways that these epigenetic factors control, and to understand which brain functions are impaired by the dysfunction of these proteins. In order to meet this aim, we work on conditional transgenic mice that lack these vital epigenetic factors in brain neurons. We perform molecular and morphological profiling on the brains of these transgenic mice, and behavioral studies to understand the role of these proteins in mamallian behavior.  

 

Techniques and methods

The laboratory employs a wide variety of techniques in order to explore our research questions. The research methods are the most state-of-the-art in the field of molecular neuroscience and include the following facilities and methods:

  • Cell culture (for culture of cell lines and primary neuronal culture)
  • Illumina high throughput sequencing
  • mouse behavioral profiling unit for profiling learning, memory, social interactions, and anxiety behaviors
  • Histology
  • Real Time Quantitative PCR
  • The departmental equipment facilities also houses several state-of-the art equipment that we regularly use, including confocal microscopes, Agilent bioanalyzer system, etc.