Department: Pharmacology, Physiology & Toxicology
Research Cluster: Neuroscience and Developmental Biology
1. Mechanisms of action of antidepressant medications
Mood disorders, including depression, are extremely common, affecting 5-10% of the population. A number of antidepressant medications are currently used to treat depression, however many patients do not respond to medication. In addition, although the immediate effects of these medications are known (most alter serotonin and/or norepinephrine neurotransmission), therapeutic effects of these drugs occur with a delay of several weeks. While the reasons for this delayed effect are not known, current research hypotheses focus on changes in synapses function and structure (plasticity). In this project, we are examining synaptic function and plasticity, and the expression of plasticity related molecules in brain areas that are affected by depression and are targets for antidepressant medications. By increasing our understanding of how antidepressant medications affect brain function, we hope to contribute to improved therapies for depression.
2. Mechanisms of memory formation
Memory formation occurs through long-lasting changes in the strength of synaptic communication between neurons. In this project we study synaptic strengthening (potentiation) in order to understand how the brain is altered during formation of new memories. We focus on the hippocampus, which is the major brain structure involved in memory formation. Our goal is to understand the cellular and molecular events that occur during memory formation, in particular, the roles of calcium-permeable ion channels and calcium regulated signaling pathways. By determining the brain mechanisms used for normal memory function we will improve our understanding of how memory is adversely affected by neurological disorders and diseases.
For a complete list of publications, visit PubMed.
Cooke, J.D., Cavender, H.M., Lima, H.K. and Grover, L.M. Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus. Psychopharmacology (Berl). 2014 Apr 30. [Epub ahead of print] (http://www.ncbi.nlm.nih.gov/pubmed/24781518)
Kim, E., Owen, B., Holmes, W.R. and Grover, L.M. Decreased afferent excitability contributes to synaptic depression during high-frequency stimulation in hippocampal area CA1. Journal of Neurophysiology 108, 1965-1976, 2012. (http://www.ncbi.nlm.nih.gov/pubmed/22773781)
Cooke, J.D., Grover, L.M., and Spangler, P.R. Venlafaxine treatment stimulates expression of BDNF protein in frontal cortex and inhibits LTP in hippocampus. Neuroscience 162, 1411-1419, 2009. (http://www.ncbi.nlm.nih.gov/pubmed/19464349)
Grover, L.M., Kim, E., Cooke, J.D. and Holmes, W.R. LTP in hippocampal area CA1 is induced by burst stimulation over a broad frequency range centered around delta. Learning and Memory 16, 69-81, 2009. (http://www.ncbi.nlm.nih.gov/pubmed/19)