Instructions for Fundamentals of Neuroscience assignment This exam is intended to determine how well you have grasped the concepts presented in class and supplemented by your readings. You can use your notes, textbooks, journals, and your handouts to help you answer these questions. Any resource except each other! All questions are in essay format, and are intended to make you think and integrate the material presented to you. In general, answers should be approximately 2 pages in length, but remember, quantity is not necessarily equivalent to quality! You are welcome, if appropriate and utile, to include figures, drawings, diagrams etc, but be wise! And all material from published sources should be cited appropriately. Please answer ALL of these questions: Question 1 – Question 2 – Question 3 – Question 4 – Question 5 – Question 6 – Question 7 –
NAME: Question 1 1) Describe three ways that the synthetic activity of tyrosine hydroxylase can be increased, and discuss differences in the mechanism and the time frame over which each of these processes works. 2) Describe how each of these processes links changes in catecholamine neurotransmission to: a) changes in neuronal activity of catecholamine neurons, and b) changes in the internal (body) or external (world) environment 3) Discuss the modulatory effects of catecholamines on their target circuits, and how each of the TH-‐regulatory processes might produce different functional changes in these modulatory effects.
NAME: Question 2 It is well-‐known that a key mechanism by which drugs increase locomotor activity (i.e. cause hyperactivity) is by increasing extracellular dopamine. In preclinical tests, investigators found that a novel compound (called “hyper”) increased locomotor activity in mice. The investigators wanted to know the mechanism by which “hyper” produced this behavioral effect and asked the question, “Is the increased locomotor activity induced by “hyper” due to an action of the novel compound to increase extracellular dopamine by inhibiting dopamine uptake via the dopamine transporter in vivo?” Based on material covered in the “Neurotransmitter Transporter” lectures, and your supplemental readings, design experiments to answer their question. Hint: Design your answer as if you were writing a short research proposal (therefore your answer should be longer than a few pages). Your research proposal should have the following sub-‐ sections: 1. Background and rationale for the proposed experiments 2. Hypothesis to be tested 3. Experiments to be carried out 4. Expected results 5. Alternative outcomes if you do obtain the expected results 6. Literature cited Note: Providing definitions of the techniques you would use is NOT a sufficient answer. Use your training in neuroscience and pharmacology to provide an answer that demonstrates critical thinking and appropriate experimental design.
NAME: Question 3 You have created a transgenic mouse which expresses an inhibitory Gi-‐coupled DREADD from the GFAP promoter. Long-‐term administration of CNO from P0-‐P21 during brain development leads to the reduction in the density of excitatory synpases in CA1 of the hippocampus. Given that astrocytes are known to secrete many proteins which regulate synapse formation, you suspect that there is an activity-‐dependent protein that is secreted by astrocytes that increases synapse density.
1) Design an experiment to prove that an astrocyte-‐secreted factor is involved in the phenotype of the GFAP-‐inhibitory DREADD mouse.
2) Assuming that you have proven that a secreted factor is responsible, design experiments to identify this secreted factor.
NAME: Question 4 In the CNS, myelin is produced by oligodendrocytes. Recently, we found that the brain-‐derived neurotrophic factor (BDNF) is important for oligodendrocyte development. Propose a research project to investigate the role of one of BDNF in neuron-‐oligodendroglia interaction, myelination, and neural circuit development in the CNS. Design a research project including the rationale (or hypothesis), the experimental approaches (methods and techniques), the expected results, and the possible explanation (their roles in the brain).
NAME: Question 5 You have found a novel therapeutic compound and are concerned that it may have off-‐target effects in the hippocampus. Provide three distinct approaches (i.e. behavioral and non-‐ behavioral) you would use to evaluate these potentially deleterious effects. Please include a detailed rationale, experimental design, and potential conclusions for each.
NAME: Question 6
You have isolated a substance from fire ants that produces a profound mechanical allodynia when injected into mice. The initial pharmacology studies demonstrate the following properties:
1. Design a series of experiments to determine the site of action of this substance:
2. Design additional experiments to determine its mechanism of action.
Fire Ant Extract
NAME: Question 7 While walking through the woods, your less-‐than-‐intelligent hiking partner scrapes the bottom of their foot (since they weren’t wearing any shoes), and complains of massive, throbbing pain an hour later. While you consider the most effective treatment for addressing this form of nociception, please provide your friend with an accurate assessment of the biochemical changes occurring in the primary afferent neurons innervating the affected tissue. Specifically, identify and characterize the kinases, kinase targets, neuronal phenotype(s), and appropriate treatment(s) needed to diagnose and remedy this issue for your intellectual troglodyte of a companion. Please cite references as needed, and yes, they are needed.