Karla Kaun, PhD

Robert and Nancy Carney Assistant Professor of Neuroscience
Department of Neuroscience
Brown University
(September 27, 2019)

How alcohol influences memory circuits to induce cravings

Few people have not experienced that craving for a glass of red wine with a nice meal or an ice-cold beer at a barbecue. But why is it that we do not generally experience that same craving for a bowl of broccoli? Dr. Kaun discussed her research using fruit flies on how alcohol cravings differ from other types of reward signal in the brain. This can have important implications for the study of addiction.

Have you ever wondered why people crave alcohol but not apples? We are wired to seek and respond to rewarding experiences, and drugs of abuse work by hijacking our brain’s reward centers. Our brains have 86 billion nerve cells with an estimated 150 trillion connections between them. The sheer number and variety of nerve cells within the brain’s reward centers, combined with their elaborate connectivity, has prevented us from understanding how drugs of abuse affect these brain circuits. My laboratory and I use fruit flies, which have only 100,000 neurons, to understand how drugs like alcohol affect the brain connections important for forming and maintaining cravings. We use an array of cutting-edge neurogenetic tools in flies to understand how intoxicating drugs like alcohol change brain molecules in the brain’s reward circuits in order to cause cravings. Combining forward genetics, transcriptomic and detailed circuit mapping approaches, we’ve shown how alcohol influences the a highly conserved cell-signaling pathway, called Notch, to affect gene expression required for memory formation. Our work provides direct evidence hat alcohol induces immediate changes in Notch signaling. This leads to gene expression changes required for neuronal plasticity in memory-encoding neurons. Activation of Notch signaling also correlates with expression of alternative transcript isoforms of key genes that regulate multiple forms of memory. This process was very dynamic, and appeared to result in different transcript isoforms of the same gene being expressed after formation of alcohol memory. This suggests that alcohol alters gene expression while memories are becoming encoded, potentially strengthening memories for alcohol. Using circuit mapping techniques, we are investigating how this molecular change can influence a dynamic shift from circuits that form memories to circuits that initiate cue-induced behavioral responses. This work reveals a highly conserved mechanism that clarifies how alcohol cravings differ from other forms of reward memories, and suggests that one of the keys to cracking circuit function is to investigate the adult roles of the molecules required for circuit development.