Neuronal circuits underlying the treatment of anxiety disorders
Description: Remembrances of traumata from the distant past range among the most stable forms of memories and have debilitating effects on the lives of those concerned. Effective treatments to attenuate such memories are scarce and the mechanisms behind successful memory extinction remain poorly understood. Moreover, with the exception of delayed behavioral assessments, reliable tools to measure the efficacy of extinction strategies for traumatic memories are currently missing. In this project, we aim to better understand remote memory extinction at a cell population-specific level and to develop a new tool to better gauge the efficacy of interventional strategies against remote fear memories. To achieve these goals, we will be using transgenic mice, which allow for inducible but persistent genetic tagging of neurons that are activated by remote memory recall. By visualizing this tag upon completion of successful memory extinction, we will first identify the neuronal subpopulations that are active during memory extinction. Next, by targeting this tag with pharmacological means to bidirectionally modulate the activity of these neurons, we will determine their causal implication in memory extinction. Lastly, by using this tag as bait, we will isolate fear extinction-relevant neurons for in-depth characterization of the molecular mechanisms associated with successful memory extinction. Here, particular emphasis will be given to the epigenetic regulation of gene expression, a fundamental process of long-lasting forms of memories. By investigating these mechanisms in two independent extinction protocols, we seek to provide proof-of-principle that successful methods of remote memory extinction are defined by a common molecular signature, which can serve as a future tool to rapidly and reliably ascertain the potential of novel treatments with the same purpose.Taken together, this project will deepen our understanding of remote fear memory extinction, and enlarge our toolbox to assess interventional strategies against traumatic memories.
Amount: CHF 316,000
Funding type: research
Funder scheme: Project funding
Start date: 2015-01-01
End date: 2017-12-31
Investigator: Gräff, Johannes
Institution: EPF Lausanne – EPFL
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 9
Funder award ID: 155898
OpenAlex ID: G5410240004