What projects are you currently working on how do you collaborate with fellow faculty members?
Work in my lab is focused on two very broad questions: How do memories form? And once they are formed, how can they be eliminated or inhibited? We know a lot about the behavioral conditions and cellular and molecular processes that are involved in normal memory formation. In my lab, we are especially interested in the mechanisms that are involved in the development and inhibition of particularly salient memories – those involving trauma or drugs of abuse. We have found that repeated exposure to cues associated with trauma or abused substances results in a weakening of the learned behavioral responses (fear or drug-seeking) through a process known as extinction.
Our lab is particularly interested in trying to promote this extinction process by pairing extinction trials with manipulations of cellular and molecular memory mechanisms. Recent work has focused on histone acetylation – we have found that general or specific histone deacetylase (HDAC) inhibitors coupled with extinction can result in a persistent suppression of these salient memories, presumably because HDAC inhibitors relax the protein complex that packages DNA, thereby promoting transcription and long-term memory formation. We focus on systemic manipulations and manipulations within a specific circuit involving the medial prefrontal cortex, amygdala and hippocampus.
There are many opportunities for fellow faculty to participate in my research. My lab is primarily a behavioral lab. We manipulate cellular and molecular processes, but we do this in vivo, with a behavioral measure as an experimental endpoint. I like to collaborate with people who are interested in some of these cellular and molecular processes (e.g., histone acetylation), but at a level of molecular analysis that is beyond the scope of what we do in my lab. For example, some of my collaborations have included researchers who help us examine how individual HDACs operate at a molecular level to regulate expression of specific genes involved in memory.
What is the most important aspect of support that OHSU provides to you currently and how would you like this or other support to grow in the future?
The main thing that OHSU has provided me is an amazing intellectual environment. It is an extremely collaborative place and I can’t count the number of collaborations that I have had with other PIs since I’ve been here. I am always open to collaborating with anyone looking to examine memory effects that may develop from pharmacological, genetic or other manipulations. A great way to foster an already collaborative environment is to continue to invest in new assistant professors who bring the latest approaches and technologies with them.
A hypothetical: If you could have one tool that would solve a seemingly impenetrable problem in your work, what would it do? You have unlimited resources to design this tool, so think big.
This is a hard one. I study learning and memory, which are unobservable processes. We can’t ask rats and mice to articulate their experiences, so we have to make inferences about learning and memory from their behavior. When you throw genetic, viral or pharmacological manipulations into the mix, you have to think very critically about situations in which your behavioral measure may reflect processes other than memory (such as sensory perception, motivation and motor performance processes). You can look at brain changes, but these, too, come with assumptions about how cellular processes (such as long-term potentiation or changes in dendritic branching) translate into memory representations. We also know that memory is extremely fallible in people, so even giving animals the ability to introspect and articulate their memories verbally would not be of much help. So the impenetrable problem in my field is getting access to an accurate neurobiological readout of what memory is. If I could wave my magic science-fiction wand, that readout is what I would like to have. But it would also mean that we wouldn’t need to answer any more questions, which would make my life much less interesting.
Want to hear more from Dr. Lattal? In 2014, he provided memory improvement tips on OPB’s “Think Out Loud.” Listen to the broadcast here.
This blog post originally appeared on OHSU’s internal “Inside the SOM” blog, authored by Rachel Shafer, Senior Communications Specialist in the OHSU School of Medicine.