DOPAMINE NEURODYNAMICS IN THE VENTRAL HIPPOCAMPUS DURING AVERSIVE LEARNING

The ventral hippocampus (vHPC) is necessary for the acquisition and recall of aversive memories. Dopamine is also a critical neuromodulator for aversive learning, yet we know little about how dopamine in the vHPC contributes to the formation of aversive memories. The current study aims to characterize the specific dopamine projections and receptor subtypes within the vHPC that underlie aversive learning. This study uses a vHPC-dependent, aversive memory task in mice called trace fear conditioning (TFC). Using a genetically encoded fluorescent sensor (GRAB-DA), we show that dopamine is released into the ventral CA1 subregion during TFC at salient timepoints. To investigate the source of dopamine in the vHPC, we induced apoptosis in two main dopaminergic projections to the vHPC, the ventral tegmental area (VTA) and the locus coeruleus (LC). We found that dopamine in the vHPC involves both the VTA and LC. Next, we altered the activity of both D1-like and D2-like receptors in the vHPC during TFC. We found that inhibiting D1-like receptors impairs memory, whereas inhibiting D2-like receptors enhances memory. These results suggest that dopamine in the vHPC during aversive learning is a dynamic process that involves multiple brain regions and receptor subtypes. Future work in our lab will combine calcium imaging with GRAB-DA to examine the impact of dopamine release on excitatory and inhibitory neural activity in the vHPC during TFC. This work is significant in that altered catecholamine release in the HPC accompanies schizophrenia, bipolar disorder and ADHD, which are often comorbid with fear and anxiety disorders.