Laboratory of Dr. Jonathan E. Ploski, Ph.D.

Associate Professor - Neural & Behavioral Sciences

Research

Dr. Ploski recently moved his laboratory to Penn State College of Medicine and joined the faculty here in the Department of Neural and Behavioral Sciences as of September 1, 2021.

 

His research areas are the following:

 

1. Molecular basis of learning and memory with a focus on attenuating maladaptive memories associated with emotional disorders. In particular, Dr. Ploski’s laboratory is interested in the molecular basis of memory modification, where he hopes treatments can be developed to enhance the induction of reconsolidation updating for therapeutic purposes.

Targeting memories has been proposed as a treatment for many psychopathologies, including Post-Traumatic Stress Disorder (PTSD). For PTSD, blocking the reconsolidation of retrieved traumatic memories may attenuate these memories, in turn reducing PTSD symptomology. However, numerous studies indicate that strong memories can be particularly difficult to disrupt. This is believed to be due to the fact that the reconsolidation process is not initiated when these memories are retrieved, rendering them impervious to agents that are intended to target the restabilization phase of reconsolidation. Strong memories essentially become resistant to being modified. The mechanisms underlying the modification resistance of strong memories are poorly understood, and the lack of understanding of these basic neurobiological mechanisms is significantly impairing the development of viable treatments to therapeutically manipulate modification-resistant circuits.

In an effort to understand the molecular basis for why weak and strong fear memories differ in their ability to be modified, Dr. Ploski’s laboratory recently determined the following: 1) that training-dependent changes in the N-methyl D-aspartate receptor (NMDAR) subunit composition occur at basal and lateral amygdala (BLA) synapses that correlate with a strong memory’s inability to be modified upon retrieval; and 2) that genetically increasing the NMDAR GluN2A/GluN2B ratio is sufficient to block retrieval-induced memory destabilization, and this prevents an existing memory trace from being modified via reconsolidation updating.    Now his team is examining if genetic overexpression of GluN2B or pharmacological agents that increase the synaptic localization of GluN2B, can enhance the modifiability of strong fear memories.

 

2. Viral vector development for preclinical and potentially clinical gene therapy purposes:  Dr. Ploski’s laboratory has identified AAV serotypes that produce high titers and transduce amygdala neurons highly efficiently. His team has also developed novel, chemically regulated genome editing systems that can be delivered to neurons in vivo, to manipulate genes. These technological achievements provide an alternative to viral-mediated shRNA delivery, which his laboratory found could have unintended negative consequences on neural function and behavior.

 

 

Complete list of Published Work: My Bibliography

 

 

Skip to toolbar