PhD position Dissection of prediction error and reconsolidation
Team Animal Models of Psychiatric disease has a vacancy for a PhD project. Dissection of prediction error and reconsolidation circuits of aversive emotional memory
Dissection of prediction error and reconsolidation circuits of aversive emotional memory
Aberrant memory processing lies at the root of a plethora of fear, anxiety and addiction disorders. Memories are not static imprints of past learning and can reinstate plasticity, to maintain relevance. Stored memories, encoded by a small number of activated neurons (memory trace), are first destabilized upon reactivation (retrieval), and afterwards restabilized in order to persist further. This restabilization, known as reconsolidation, is the brain’s innate process for fundamentally revising learnt behavior. Disrupting the reconsolidation of dysfunctional memories holds great potential for treatment of disorders that result from a hyper-responsive memory system.
Hypothetically, all memories can undergo reconsolidation, but it has been experimentally observed that this process is not ubiquitous and is contingent on destabilization of memory during reactivation. Destabilization strongly depends on new information present during a reactivation session, and the mismatch between what is expected and the actual situation present during initial learning and reactivation is termed prediction error (PE). Human studies have shown that reconsolidation of human fear memory could be disrupted by the pharmacological antagonism of noradrenergic β-receptors by propranolol. However, this propranolol-mediated disruption of reconsolidation occurs only in the presence of PE during reactivation and the brain areas that generate these PE-signals as well as the downstream mechanisms that underlie propranolol-mediated disruption of memory are unknown.
In this project we will use a multilevel approach in transgenic mouse lines to causally identify the brain region(s) generating aversive PE-signals to neurons of the memory trace and elucidate the molecular mechanisms that mediate propranolol disruption of reconsolidation after PE. This project is supervised by Dr. Rao-Ruiz in the group of Prof. Spijker; hosted by the Department of Molecular and Cellular Neuroscience at the VU, in close collaboration with the Kindt group (Psychology, UvA). Gross salary is according to the standard scaling of promovendus (scale 85-0 extending to 85-3) for a 4-year project.
Main analysis tools:
1. Transgenic mouse lines to tag and manipulate specific cells participating in memory processing
2. Rodent surgery, optogenetics and viral-vector interventions
3. Laser Capture Microdissection (LCM) coupled to label-free quantitative proteomics
4. Molecular techniques such as immunohistochemistry and immunoblotting
We are looking for candidates that hold, or will soon hold, a master degree in Neuroscience or Molecular Biology, preferably with hands-on experience in the methods listed above. We expect a pro-active and motivated and curiosity-driven attitude to pursue a career in Neuroscience, the capability to critically reflect upon experiments, excellent command of English and good communication and presentation skills to guarantee efficient information exchange. Suitable candidates will be called for interview.
MIND: We have currently made a selection for interviews, hence applications are halted for the moment.