One of the most intriguing questions in neuroscience is how individual sensory, temporal, and emotional components of an experience are encoded into rich, persistent memories. Not only do these memories make up our personal narrative, but they are central to adaptive behavior. Healthy emotional learning allows us to predict and avoid danger and approach reward and safety. A distributed network of cortical and subcortical brain areas participate in successful memory formation, and dysfunction in these circuits leads to maladaptive behavior observed in a number of mental health disorders, including post-traumatic stress disorder (PTSD), anxiety disorders, schizophrenia, and addiction. Our work seeks to determine how the prefrontal cortex, hippocampus, and amygdala functionally interact to form, store, and retrieve emotional memories.
Past and present support for our work comes from:
The National Institutes of Health
The National Science Foundation
The Whitehall Foundation
The Charles E. Kubly Mental Health Research Center
Prefrontal-temporal lobe communication during fear memory formation
The ability to predict future events based on available cues in the environment is crucial for adaptive behavior. This requires animals to create, maintain, and use mental representations, or memories, of environmental elements that are no longer present.
In the case of trace fear conditioning, the association of an auditory cue and aversive footshock that are separated by several seconds requires a distributed network of brain areas needed for episodic memory and threat processing. Of these areas, we have found that the prefrontal cortex shows increased neuronal activity to the cue, activity that persists throughout the empty "trace interval" until the shock is delivered. We have also shown that this activity is necessary for learning. The challenge now is to determine how this gap-bridging activity is used within the broader learning network to support learning.
To address this challenge, we use optogenetic and chemogenetic tools in combination with electrophysiology and calcium imagine in awake, behaving animals to manipulate and record neuronal activity within specific brain connections between the prefrontal cortex, hippocampus, and amygdala.
Sex differences in fear memory formation
Women are more likely than men to be diagnosed with PTSD and anxiety disorders, but the neurobiological basis of this sex difference is not known. In the laboratory, female and male rodents engage similar circuitry in support of learning, but are differentially sensitive to certain neuromodulators during memory formation. We recently found that the neuropeptide PACAP, acting in the prefrontal cortex, contributes to the strength of a fear memory in females, but not males. Therefore, this line of research aims to determine how PACAP and other neuromodulators affect emotional learning in each sex and the extent to which ovarian hormones control these sex differences. A more thorough understanding of the mechanistic differences between the sexes in how fear memories are formed and stored will help us understand sex differences in mental illness and ultimately devise more effective individualized treatment.