The laboratory of Brady Atwood, PhD, is focused on understanding the functions of specific synapses in the brain and how these functions are impacted in disease states. Synapses are the connections between brain cells and the principal sites of information transfer between cells. Synaptic transmission determines animal behavior and is highly plastic. This synaptic plasticity allows for an animal’s learning and adaptation. However, many disease states can alter synaptic plasticity which can negatively influence learning and behavior. The Atwood laboratory uses a multidisciplinary approach, from molecular analyses to studies of animal behavior, to elucidate the function of specific synapses in brain circuits that influence motivated and habitual behaviors. In addition, we are interested in how diseases and conditions such as drug addiction, obesity, and neurodegeneration affect how these same synapses function.
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The dorsal striatum is a brain region that controls actions—both ones that are driven by a motivation to accomplish a specific goal and ones that are more habitual. The development of addiction is associated with alterations in dorsal striatum function and a variety of neurodegenerative diseases, including tauopathies, impair normal function of this brain region as well. We are seeking to determine the molecular mechanisms that underlie drug- and tauopathy-induced changes in dorsal striatal function. Dorsal striatal activity is driven by synaptic inputs from other brain regions such as the cortex, thalamus and amygdala. Our work focuses on these various inputs and seeks to mechanistically determine how drugs of abuse, obesogenic diets and tauopathies selectively affect only some synaptic inputs, while sparing others. As we discover synapses that are uniquely impacted, we also look to identify the specific roles of those synapses in behavior. In addition, we are also very interested in mechanistically understanding how in utero drug exposure affects offspring behavioral outcomes. As the opioid epidemic has grown, more babies are born to mothers that were using opioids during pregnancy. Surprisingly very little is known about in utero exposure’s long-term effects and we hope to provide a greater understanding of the genetic, anatomical, physiological and behavioral outcomes.
In our work we use mouse models of addiction, in utero drug exposure, obesity and tauopathies. We employ a variety of mutant mouse lines in combination with in vitro and in vivo optogenetic strategies to selectively probe and modulate specific synapses in the brain. We have a multidisciplinary approach using brain slice electrophysiology, quantitative gene expression measures, proteomic, transcriptomic, viral vector manipulations, microscopy and many different behavioral analyses. We have a particular interest in the roles of opioid, cannabinoid and adenosine neurotransmitter receptors in influencing synaptic function. Combining these various approaches into studying very specific synapses, we can determine molecular “fingerprints” of synapses that render them susceptible or resistant to disease-related functional changes. The long-term goal is that by knowing what these fingerprints are, we will be able to design targeted therapeutics to prevent or undo disease-induced molecular dysfunction.
The Atwood Lab, a team of faculty, postdocs, graduate students and lab technicians, regularly collaborate with IU School of Medicine researchers.
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In the News
Effects of in utero opioid exposure research in the Atwood Lab was featured in Indiana University's Responding to the Addictions Crisis Grand Challenge.