Atwood Lab

Researchers within the Atwood Laboratory are fascinated by how life experiences change the way humans act. In particular, they are interested in how drugs of abuse, diet, stress and pain influence the types of actions humans perform. The focus of the Atwood Lab is on the molecular mechanisms and brain circuits that are specifically impacted by these substances and experiences.

Under the direction of Brady Atwood, PhD, the Atwood Lab use mouse models of drug abuse, obesity, stress and pain, in combination with state-of-the-art neuroscience methodologies, to:

1) Identify the specific molecules that are altered
2) Determine changes in neuron function and synaptic plasticity
3) Identify affected neurocircuits
4) Manipulate neurocircuits to determine their behavioral relevance

The goal of the Atwood Lab is for their findings to translate to novel therapeutic interventions to improve the lives of those that suffer from addiction, obesity, stress disorders and chronic pain.

Active Research

The opioid epidemic has recently captured international attention, but addiction and drug and alcohol abuse have been a significant problem for a very long time. There are currently few highly effective therapeutics for treating addiction; therefore, there is a great need for new treatments.

The Atwood Lab focuses on the impact of opioids and alcohol on neurotransmission in the dorsal striatum (caudate and putamen nuclei in humans), a brain region that controls goal-directed and habitual actions. Researchers are specifically exploring how these substances change the connections between this brain region and other parts of the brain, including the cerebral cortex and the thalamus. The primary finding is that these substances have a very unique effect on the connection between the insular cortex and the dorsolateral striatum (putamen). The insular cortex is an interoceptive part of the brain, meaning it processes awareness of the body’s current state (intoxication, drug cravings, hunger, pain, etc). The dorsolateral striatum controls habitual behaviors.

The Atwood Lab is working to understand the significance of the connection between these two parts of the brain using in vivo optogenetics and brain slice electrophysiology in combination with mutant mice. This allows the research team to control the activity of this connection in behaving animals, and also to probe its functionality at the cellular level using microscopy and in vitro techniques. The lab is studying the molecular changes that are unique to this connection that may explain its sensitivity to drugs of abuse. A variety of mouse behavioral tests are used to determine behavioral outcomes of manipulating this connection. The research team hopes to identify a novel therapeutic target to undo the changes that drugs produce in this neurocircuit.

Other interests of the lab include how diet, pain and stress have both similar and divergent effects on these neurocircuits as drugs of abuse. In addition, the lab is exploring whether or not a genetic predisposition to drug abuse produces intrinsic alterations to dorsal striatal neurotransmission.

Work within the Atwood Lab is currently funded by multiple grants from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism.

Educational Opportunities

The Atwood Lab is always looking for enthusiastic volunteers to work in the laboratory. Interested applicants should send a curriculum vitae or resume to Dr. Atwood.

Two graduate student positions are currently available within the Atwood Lab. For more information on PhD training at IU School of Medicine, visit the PhD Training page of this website. In addition, openings for physician scientist trainees are available through the Medical Scientist Training Program (MD/PhD).

Publications

Munoz, B., Fritz, B.M., Yin, F., Atwood, B.K.  Alcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum. Nature Communications. In press.

Fritz, B.M., Munoz, B., Yin, F., Bauchle, C., Atwood, B.K. A high-fat, high-sugar ‘western’ diet alters dorsal striatal glutamate, opioid, and dopamine transmission in mice. Neuroscience, Epub December 28, 2017. PMID: 29289718.

Mateo, Y., Johnson, K., Covery, D.P., Atwood, B.K., Wang, H.-L., Zhang, S., Gildish, I., Cachope, R., Bellocchio, L., Guzman, M., Morales, M., Cheer, J., Lovinger, D. M. Endocannabinoid Actions on Cortical Terminals Orchestrate Local Modulation of Dopamine Release in the Nucleus Accumbens. Neuron, 96(5):1112-1126 (2017). PMID: 29216450

Atwood, B.K., Lovinger, D.M. Endocannabinoid-Dependent Synaptic Plasticity in the Striatum. Endocannabinoids and Lipid Mediators in Brain Functions. 109-153 (2017)

Gremel, C., Chancey, J., Atwood, B.K., Luo, G., Neve, R., Ramakrishnan, C., Deisseroth, K., Lovinger, D.M., Costa, R. Endocannabinoid modulation of orbitostriatal circuits gates habit formation. Neuron. 90(6):1312-1324 (2016). PMID: 27238866

Atwood, B.K., Lovinger, D.M., Mathur, B.M. Presynaptic long-term depression mediated by Gi/o-coupled receptors. Trends in Neurosciences. 37(11): 663-673 (2014). PMID: 25160683

Atwood, B.K., Kupferschmidt, D.A., Lovinger, D.M. Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum. Nature Neuroscience. 17(4): 540-548 (2014). PMID: 24561996

Atwood, B.K., Wager-Miller, J., Haskins, C., Straiker, A, Mackie, K. Functional selectivity in CB(2) cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB(2) ligands. Molecular Pharmacology. 81(2): 250-263 (2012). PMID: 22064678

Atwood, B.K., Straiker A., Mackie, K. CB(2) cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. Neuropharmacology. 63(4): 514-523 (2012). PMID: 22579668

Atwood, B.K., Straiker, A., Mackie, K. CB(2): Therapeutic target-in-waiting. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 38(1): 16-20 (2012). PMID: 22197668

Atwood, B.K., Lopez, J., Wager-Miller, J., Mackie, K., Straiker, A. Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis. BMC Genomics. 12:14. (2011). PMID: 21214938

Atwood, B.K., Lee, D., Straiker, A., Widlanski, T.S., Mackie, K. CP47,497-C8 and JWH073, commonly found in ‘Spice’ herbal blends, are potent and efficacious CB(1) cannabinoid receptor agonists. European Journal of Pharmacology. 659(2-3): 139-145 (2011). PMID: 21333643

Atwood, B.K., Mackie, K. CB2: a cannabinoid receptor with an identity crisis. British Journal of Pharmacology. 160(3): 467-479 (2010). PMID: 20590558

Atwood, B.K., Huffman, J., Straiker, A., Mackie, K. JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. British Journal of Pharmacology. 160(3): 585-593 (2010). PMID: 20100276

Faculty Research Team

Brady K. Atwood, PhD

Brady K. Atwood, PhD

Assistant Professor of Psychiatry