This week we profile a recent publication in the International Journal of Neuropsychopharmacology
from the laboratory of Dr. Anthony G. Phillips (pictured) at UBC.
Could you provide a brief overview of your lab’s current research focus?
This article is the latest in a series of publications on the role of synaptic plasticity (both long-term potentiation-LTP and long-term-depression LTD) in learning and memory. In collaboration with my colleague Yu Tian Wang we have focused on the role of LTD in a range of tests of learning and memory. This body of work has implicated LTD in behavioural and cognitive flexibility as well as natural forgetting. We are also actively engaged in the development of novel drugs to restore cognitive function in brain disorders ranging from dementia to schizophrenia.
What is the significance of the findings in this publication?
The paper by Ashby et al., focuses on an interesting learning phenomenon called Latent inhibition (LI). In LI, prior repeated presentation of inconsequential stimuli disrupts subsequent conditioning of such stimuli with reinforcement. The absence of LI in many individuals living with the challenges of schizophrenia is of great interest, as is the conjecture that abnormal synaptic plasticity may contribute to the cognitive deficits that are defining features of this disorder. Our paper is perhaps the first study to successfully link these three phenomena.
Specifically, we show that blockade of LTD with an interference peptide developed by our UBC colleague Yu Tian Wang, enhances LI, to the point where new learning does not take place. Remarkably, control rats given the same drug treatment show perfectly normal learning, which rules out sensory or motor factors along with general learning deficits as side effects of the interference peptide. We also propose that over active LTD processes may account for the weak LI effects seen in schizophrenia.
What are the next steps for this research?
Collectively these data suggest that both disruption and enhancement of LTD can have profound effects on models of learning, memory and cognitive flexibility. The task before us is to translate our growing understanding of the molecular biology of synaptic plasticity into new drugs that can normalize LTD and LTP in brain. We also have a very active research project on the role of synaptic plasticity in addiction and have strong evidence that LTD plays an important role in substance use disorders.
This research is funded by the Canadian Institutes of Health Research.
