PROJECT ABSTRACT
The ability to form aversive memories (e.g., connecting stimuli in the environment with the negative events they
predict) is crucial to survival and is well-conserved across species. Alterations in this system, however, can lead
to maladaptive or inappropriate fear responding outside of situations in which a fear response is warranted. This
“generalized” fear response, in which fearful behavior is expressed outside of the context or environment in
which it was acquired, is a hallmark symptom of several human neuropsychiatric disorders like post-traumatic
stress disorder (PTSD) and generalized anxiety disorder (GAD). The inability to appropriately use context to
guide fear responding is a common process that, when treated, could target symptomology underlying several
disorders, most of which cause significant distress to the afflicted. Most research on the encoding and retrieval
of contextual processing in fear memory has focused on subcortical regions like the hippocampus and the
amygdala. Recent data has begun to suggest a critical role for the retrosplenial cortex (RSC) in the acquisition
and expression of these memories. Previous work has primarily used spatially and temporally imprecise
manipulations of the RSC, making it difficult to understand the exact role of this relatively large structure in
encoding and retrieval of both the event-related (i.e., “what”) and context-related (i.e., “where”) aspects of
aversive memory. The overarching hypothesis of this proposal is that the anterior region of the RSC (i.e., the
aRSC) is important for encoding of the event-related aspects of memory (the “what” memory) and that the
posterior region (i.e., the pRSC) independently and dissociably encodes the context-related information (that
“where” memory). In Specific Aim 1, we will examine differential contributions of aRSC and pRSC to the to the
independent formation of event-related and contextual memory, and their subsequent association, via a modified
form of contextual fear conditioning. In Specific Aim 2, we will examine the contributions of both regions to the
retrieval of event-related and contextual memory, using both contextual fear conditioning and trace fear
conditioning (a type of cued fear conditioning that is crucially dependent on the RSC). In all studies, neurons in
either aRSC or pRSC will be optogenetically silenced, a technique that allows for unprecedented spatial and
temporal precision. This temporary and reversible inactivation will allow for examination of the type of information
processed within the RSC, as well as for the discrete roles of the RSC during aversive event-related and
contextual memory formation. By investigating the neural substrates that support these forms of learning, this
work could identify a new target in treating disorders in which the learning controlled by the RSC is likely
dysregulated.