Ron Lab: from genes to behavior

Our Research

Harmful, excessive use of alcohol has a severe impact on society and is one of the major causes of morbidity and mortality in the population. Unlike other drugs of abuse, alcohol does not have a well-defined site of action. Thus, mechanisms that underlie alcohol’s actions in the brain are poorly understood, and available medications for alcohol use disorders are limited. My lab is interested in elucidating molecular neuroadaptations that occur in the adult brain in response to alcohol exposure. Our long-term goal is to identify novel targets that could be developed as therapeutics to treat alcohol abuse disorders including excessive alcohol intake, seeking and relapse. To do so, we combine molecular, genetic, and behavioral paradigms in rodents to address the following questions:

  1. Which neural pathways drive the transition from social drinking to excessive, uncontrolled alcohol intake, regardless of negative consequences, and how can this transition be prevented? 
  2. What are the mechanisms that prevent the majority of social drinkers from developing alcohol abuse disorders?
Illustration showing a comparison between excessive drinking and social drinking. On the left, multiple martini glasses grouped together represent excessive drinking, with a green arrow pointing toward the center. In the middle is a traffic-light style control with three circular buttons labeled green “GO,” yellow, and red “STOP.” On the right, a single martini glass represents social drinking, with a red arrow pointing toward it. The label “LTP” appears beneath the left side.

 

A collage of images related to neuroscience and substance use. At the top is a complex molecular signaling pathway diagram with labeled proteins and arrows. Below left is a cartoon gray mouse with droopy eyes holding a foamy mug of beer, appearing tired or intoxicated. Below right is a schematic diagram of a rodent brain with color-coded regions (such as PFC, NAc, VTA, BLA, and hippocampus) connected by arrows indicating neural pathways. At the bottom is an illustration of an open prescription pill bottle w
A detailed schematic summarizing Ron Lab findings (2000–2026) showing intracellular signaling pathways in striatal neurons that regulate alcohol-related behaviors. The diagram illustrates dopamine D1 receptor, NMDA receptor (GluN2B), BDNF/TrkB, and GDNF/RET signaling converging on kinases (Fyn, PKA, PI3K, AKT, ERK, mTORC1/2), phosphatases (PTPα, STEP), small G proteins (H-Ras, Rac1, RhoB), and scaffolding proteins (RACK1), leading to changes in translation and CREB-dependent transcription. Green stars indic

Current Areas of Interest

  1. Identification of the mechanisms and circuitries underlying the unique role of brain-derived neurotrophic factor (BDNF) in alcohol-dependent behaviors.
  2. Determining the mechanisms and circuitries underlying mTORC1’s activity in heavy alcohol use and habit.
  3. Elucidating the role of kinases, including Fyn kinase and PKA, in normal CNS functions and in neuroadaptations underlying addiction.
  4. Identifying the role of small G proteins in neuroadaptations underlying alcohol use disorder.

Tools

The Ron lab utilizes a wide range of molecular, biochemical, and behavioral techniques to uncover the molecular mechanisms that underlie alcohol use and abuse disorders.

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Molecular Biology and Biochemistry

We use both classical (Western- blot, ELISA, RT-PCR, qPCR,  immunoprecipitation (IP), co-IP, immunohistochemistry) and state-of-the-art and newly developed molecular tools (RNA-seq, microRNA-qPCR, etc.) to assess the levels of mRNA and microRNA, detect epigenetic changes, and examine protein levels, localization and interactions in specific brain regions or in specific subpopulations of neurons. We also utilize virus-mediated gene delivery to knockdown or overexpress genes in brain regions and neurons of interest. We employ fractionation techniques to isolate cellular compartments, such as nuclei, lipid rafts and synapses. We further use polysomal fractionation, a procedure that allows us to specifically study transcripts bound to ribosomes (i.e. mRNA undergoing transcription). We use Scholl analysis to study neuron morphology.

Behavior

We use rodents (mice and rats), including numerous transgenic mouse lines, to study the involvement of specific pathways and circuitries in alcohol use disorders. We modify gene expression in isolated brain regions and within specific neural circuits using viral-mediated gene delivery. We also use transgenic reporter mouse lines in combination with Cre-dependent DREADDs to exogenously excite or inhibit neuronal subpopulations or specific circuits. To assess the behavioral effects of these genetic manipulations, we use a variety of paradigms of voluntary alcohol drinking. We use the two-bottle choice with continuous access to alcohol paradigm to mimic moderate alcohol intake and the two-bottle choice with intermittent alcohol access paradigm to model excessive or binge-like drinking behaviors. Mice and rats may also undergo alcohol self-administration experiments, which allow us to study motivation for alcohol, as well as extinction and relapse responses. To assess the hedonic or aversive properties of alcohol and other drugs, we use conditioned place preference or aversion procedures. We also incorporate other methods to assess alcohol-related behaviors, such as alcohol-induced behavioral sensitization, anxiety-like behaviors (open field, elevated-plus maze, light\dark box), ataxia (rotarod), sedation (loss of righting reflex) compulsivity (Y maze) and sociability (three-chamber and open field social interaction).
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