and Abstract Fear and trauma-related disorders affect millions of people in the United States and throughout the world each year. While the symptomatology in these disorders is well-characterized, the neural circuits which encode trauma are not. This proposal will provide a critical insight into these circuits by dissecting how a discrete pathway from the ventral hippocampus to the hypothalamus controls fear memories.
Aim 1 will use cutting- edge retrograde viral targeting techniques along with chemogenetics to elucidate how silencing this circuit modulates fear memories in males and females.
Aim 2 will use the same retrograde viral strategy from Aim 1 along with a genetically encoded calcium indicator and fiber photometry to reveal how circuit activity shifts from fear acquisition to fear memory retrieval.
Aim 3 will examine how silencing this circuit alters trans-synaptic transcriptional activity in the hypothalamus. This proposal will reveal a novel neural circuit mechanism for fear memories. It will provide fundamental insights into a high-value target for innovative treatments of fear and trauma-related disorders.
This proposal will characterize how a ventral hippocampal to hypothalamic circuit modulates stress and fear memories. It will decipher how this circuit contributes to fear learning and memory, shifts activity in response to fear acquisition vs. retrieval, and regulates hypothalamic neuropeptide levels. This proposal will reveal how a discrete hippocampal circuit modulates stress and fear, providing better insight into the neural circuits that may play a critical role in fear and trauma-related disorders.
