University of New Hampshire
Biomedical Sciences: Medical and Veterinarian Science
Mentor: Dr. Arturo Andrade, Department of Biological Sciences
Localization of the 37A Isoform of the Presynaptic N-Type Calcium Channel Which Plays A Role in Anxiety
Anxiety is a pervasive human health problem, that nearly 20% of the American population has been diagnosed with an anxiety-related disorder including obsessive compulsive disorder, posttraumatic stress disorder and phobias. The cortex, amygdala, and hippocampus are areas of the brain that have been involved in anxiety disorders. Current medications to treat these disorders are often unspecific because they target areas of the brain that are not related to anxiety, thereby creating undesirable effects. Presynaptic N-type calcium channels are molecules that control communication between neurons throughout most brain areas, thus neuronal activity. N-type calcium channels are multiexonic genes that undergo alternative splicing. Of particular interest is a pair of splice isoforms, 37a and 37b, because a mouse model that lacks the expression of the 37a isoform shows reduced anxiety-like behaviors. To understand how the 37a splice isoform regulates anxiety-like behavior, we will determine where this isoform is located in the cortex, amygdala, and hippocampus. Previous studies have shown that neurons expressing the peptide cholecystokinin (CCK) utilize almost exclusively N-type calcium channels to regulate the neuronal activity of those brain areas. Here we hypothesize that the 37a isoform is localized in CCK-expressing neurons. To test this hypothesis, we will use a transgenic mouse model that contains the red fluorescent protein in CCK-expressing neurons. We will dissociate brain tissue from these mice, then we will use cell sorting to select red neurons. Next, we will utilize RNA extraction, and perform RT-PCR to identify the 37a isoform. If the 37a isoform is present in CCK-expressing neurons, it would represent a target to treat anxiety disorders.