GILMARTIN LAB
Current Projects
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 imaging 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.
Neural biomarkers of cognitive decline in a rat model of Alzheimer's Disease
Alzheimer’s disease (AD) is a chronic, progressive disease that affects 1 in 9 people over the age of 65 - a number expected to double in the next 25 years. Women are disproportionately affected by AD and cycling ovarian hormones may play a role given that perimenopause coincides with the preclinical onset of AD and compounds the risk for AD in women. Perimenopause may be a period of therapeutic opportunity and early detection is crucial. However, we still know very little about the neurophysiological effects of sex hormones on cognitive systems and their interaction with AD-related pathology. The lack of data is a major impediment to developing effective treatments that counteract negative health outcomes in aging individuals. This line of research will determine the effects of ovarian hormones and AD pathology on neural signatures of working memory in the prefrontal cortex (PFC), an area of the brain that is implicated in the cognitive and emotional shifts in perimenopause and is a target of early pathology in AD and related dementias in both sexes.