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Name __________KEY___________________ Nsci 4100: Development of the Nervous System 2015 Final Examination On your scantron answer sheet, enter your name (last name, space, first name), internet ID (X.500 name) and student number. Please do it now!!! Questions in blue are reused from the first two midterm exams. Class 2 neuro 101 1. The major excitatory neurotransmitter in the central nervous system is … A. dopamine B. epinephrine C. ϒ-aminobutyric acid (GABA) D. glutamate E. serotonin 2. The most typical sequence of flow of information through a neuron is … A. dendrite > soma > axon > synapse B. synapse > axon > soma > dendrite C. soma > dendrite > axon > synapse D. dendrite > axon > soma > synapse Class 3 & 4 embryology 3. Neurons in the peripheral nervous system develop from what primary germ layer? A. mesoderm B. entoderm C. ectoderm D. More than one of the above are correct. 4. In the brainstem, the column of neurons that connects to muscles derived from somites are found … A. ventrally near the midline. B. dorsally near the midline. C. laterally. D. in no consistent position along the length of the brainstem. 5. Cells in the midline of the neural plate will form what cell group after neurulation? A. floor plate B. roof plate C. neural crest D. alar plate E. More than one of the above are correct. 6. Sensory neurons that are receptors for pain in the skin of your arm developed from … A. neural crest B. cerebral cortex C. alar plate D. basal plate E. More than one of the above are correct. Nsci 4100 – Final Exam page 2 Class 5 induction 7. In the frog embryo, the cells of the dorsal lip of the blastopore mostly will become … A. endoderm B. mesoderm C. skin D. nervous system E. More than one of the above are correct. 8. In early ectoderm, BMP4 … A. promotes expression of Zic1. B. activates the Erk signaling cascade. C. causes activation (phosphorylation) of Smad. D. causes degradation of Smad. E. More than one of the above are correct. Class 6 & 7 regionalization 9. Which of the following is NOT true about early regionalization? A. Inhibiting BMP signaling causes neural induction and the caudalization of the neural plate at the same time. B. The neural plate is prevented from taking on a caudal fate partly by Wnt inhibitors. C. Retinoic acid plays a role in caudalizing the early neural plate. D. -catenin and LEF/TCF transcription factors play a central role in Wnt-mediated gene regulation. E. More than one of the above are NOT true. 10. Which of the following is true about rhombomeres? A. Each rhombomere expresses only one of the many Hox genes. B. Each rhombomere produces sensory neurons for a specific cranial nerve. C. Retinoic acid, via its receptors, directly regulates transcription of Hox genes in some rhombomeres. D. FGFs and retinoic acid are both expressed within the rhombomeres themselves. E. More than one of the above are correct. 11. Which of the following is NOT true about the early regionalization of the central nervous system? A. The midline in the neural plate becomes the ventral side of the neural tube. B. The anterior-posterior axis of the central nervous system is always straight during embryogenesis. C. The position of a neural progenitor cell plays a large role in the fate of neurons and glia that this progenitor cell produces. D. The telencephalon and hypothalamus include the most rostral part of the central nervous system. 12. Which of the following is NOT true about the isthmic organizer? A. Its formation requires repressive interactions between two transcription factors that are expressed in the rostral and caudal halves of the brain. B. Implanting Fgf8-soaked beads mimics the effects of transplanting the isthmic organizer into the caudal diencephalon. C. It is required for the patterning of the thalamus. D. It is required for the patterning of the midbrain. E. More than one of the above are NOT true. Nsci 4100 – Final Exam page 3 Class 9 & 10 cell division 13. It has been suggested that the transcription factor Emx2 promotes symmetric cell divisions. If Emx2 was overexpressed in cortical progenitor cells in the early mouse embryo, what difference compared to controls would you expect to see later in development? A. a larger cortex B. a smaller cortex C. an increased percentage of deeper layer cortical neurons and reduction in superficial layer neurons D. an increased percentage of superficial layer cortical neurons and reduction in deeper layer neurons 14. Which of the following statements regarding the length of the cell cycle in the developing nervous system is true? A. The length of the entire cell cycle remains relatively constant in the neural tube until a cell ceases division and differentiates. B. The length of the cell cycle progressively increases as development progresses due primarily to an increase in the length of G1 phase. C. The length of the cell cycle progressively increases as development progresses due primarily to an increase in the length of G1 and G2 phases. D. The length of the cell cycle progressively increases as development progresses due primarily to an increase in the length of G1, G2 and S phases. E. The length of the cell cycle progressively decreases as development progresses due primarily to a decrease in the length of G1, G2 and S phases. 15. Which of the following statements regarding the role of Shh in cell division in the developing nervous system is true? A. Shh promotes division of external granule layer cells in the cerebellum. B. Shh reduces cell division in retina by promoting the onset of differentiation. C. Shh reduces cell division in the spinal cord by blocking the Wnt pathway. D. Shh promotes cell division in the spinal cord by activation of the MAPK (Erk) pathway via activation of the Shh receptor. AB E. More than one of the above are correct. 16. Which of the following is true regarding neural progenitor cells at the start of the G1 phase of the cell cycle? A. The level of expression of cdk4 is low. B. The level of expression of cyclin D is low. C. The level of expression of cyclin D is high. D. The level of expression of cyclin B is high. E. More than one of the above are correct. Class 11 & 12 cell migration 17. Injection of a short peptide fragment of fibronectin containing the RGD amino acid sequence into the mesoderm next to the neural tube in a chick embryo is likely to … A. increase neural crest cell migration. B. decrease neural crest cell migration. C. promote neural crest cell differentiation. D. increase skin pigmentation. Nsci 4100 – Final Exam page 4 18. In the developing cerebellum … A. cells migrate from the pial surface towards the ventricle. B. cells migrate from the ventricular surface towards the pia. C. cells migrate from the midline towards the lateral side. D. cells migrate at random in all directions. AB E. More than one of the above are correct. 19. Immunoglobulin-like cell adhesion molecules require calcium (Ca++) in order to bind. True or false? A. true B. false 20. Where is reelin expressed in the developing cortex? A. subventricular layer B. subplate C. cortical plate D. marginal layer E. More than one of the above are correct. Class 17 & 18 cell fate 21. Rod photoreceptors are generated just after birth in the rodent retina. Imagine that you could isolate progenitor cells from the newborn retina and transplant them to an embryonic day 12 retina, an age at which ganglion cells are just starting to be born. What cell type(s) would you expect the transplanted progenitor cells to generate? A. rod photoreceptor cells first, probably followed by glia B. retinal ganglion cells first, probably followed by other retinal cell types C. only rod photoreceptor cells D. only retinal ganglion cells E. The transplanted cells would most likely be inhibited from generating differentiating cells in the new environment. 22. Proneural factors … A. promote neural progenitor cell division. B. are expressed as the result of Notch activation. C. bind E-box sequences in the regulatory regions of target genes. D. bind the Notch protein and block Notch signaling. E. More than one of the above are correct. 23. Which of the following statements is true regarding the floor plate? A. Floor plate cells are directly derived from cells of the notochord. B. Floor plate cells secrete Sonic hedgehog. C. Motor neurons develop directly from cells of the floor plate. D. Primary sensory neurons develop directly from cells of the floor plate. E. More than one of the above are correct. 24. Notch activation in developing neural tube promotes expression of … A. Delta B. proneural genes C. Hes transcription factors D. Numb E. More than one of the above are correct. Nsci 4100 – Final Exam page 5 Class 20-23 mechanisms of movement & guidance 25. Which of the following is NOT a function of an actin regulatory protein? A. Caps actin filaments to block polymerization. B. Severs actin filaments into fragments. C. Elongates an actin filament by inserting an actin monomer into the wall of a filament. D. Crosslinks actin filaments into a network of filaments. E. Connects actin filaments to plasma membrane proteins. 26. Ena/VASP proteins … A. are required for neurons to form neurites. B. are microtubule binding proteins (MAPs). C. are in the highest concentration around the nucleus in newly postmitotic neurons. D. are motor proteins. E. More than one of the above are correct. 27. Neuropilin is … A. a cell adhesion molecule that binds by homophilic interactions. B. a secreted factor that repels some growing axons. C. a secreted factor that attracts some growing axons. D. a cell surface receptor for semaphorin. 28. Which of the following factors functions as a repellant guidance cue for some motor neuron axons as they grow into the limb? A. semaphorin3A B. ephrinA2 C. netrin D. nerve growth factor AB E. More than one of the above are correct. 29. Which of the following is NOT an important regulator of actin dynamics at the leading edge of a growing axon? A. actin concentration B. Arp2/3 C. ADF/cofilin D. capping protein E. All of the above are important. (i.e. None of the above is the correct answer.) 30. Actin monomers at a certain concentration will self-polymerize into filaments independent of an energy source. True or false? A. true B. false 31. Linker proteins link microtubules to transmembrane adhesion receptors. True or false? A. true B. false Nsci 4100 – Final Exam page 6 32. Commissural neurons in the vertebrate spinal cord normally express Robo1 and cross the midline in the floor plate. What phenotype would be expected with a knockout of Robo1? A. Commissural axons would not grow towards the floor plate and would not cross the midline. B. Commissural axons would grow towards the floor plate, but would not cross. C. Commissural axons would grow towards the floor plate, would cross, and then would likely recross at random intervals as they grow rostrally in the spinal cord. D. Commissural axons would grow towards the floor plate, would cross, and then would fail to grow further. E. No abnormalities would be expected. Class 24 & 25 specificity 33. Eph proteins are … A. receptor tyrosine kinases. B. ligands for Trk receptors. C. secreted, and often function in gradients. D. extracellular matrix proteins found in some parts of the developing nervous system. E. More than one of the above are correct. 34. Cell adhesion molecules like N-CAM or L1 can have varying amounts of polysialic acid (PSA). What is the likely effect on growing axons of having more PSA associated with axonal CAMs? A. Axon-substrate adhesion will be reduced. B. Axon-substrate adhesion will be increased. C. Axons will be repelled. D. Axons will detect a tropic factor and be attracted to its source. 35. In chick embryos, axons from ganglion cells on the nasal side of the retina normally synapse with cells in the posterior region of the contralateral tectum. Which of the following statements regarding the growing axons of these cells is true? A. Axons from these cells are repelled by cells in the anterior region of the tectum. B. EphrinA signaling in anterior tectum promotes the growth of these axons, which drives them towards the posterior tectum. C. EphrinA signaling in anterior tectum repels these axons from the anterior to posterior tectum. D. EphrinA signaling has a minimal role in directing these axons to their target. E. More than one of the above are correct. 36. Which of the following receptor-ligand pairs has NOT been implicated in development of the topographic pattern of retinotectal connections? A. EphA - ephrinA B. EphB - ephrinB C. Robo - Slit D. Ryk - Wnt E. All of the above have been implicated. Class 26 & 27 cell death / trophic factors Nsci 4100 – Final Exam page 7 37. In developing rodents, somewhat over 800 retinal ganglion cells give rise to axons that transiently project to the ipsilateral superior colliculus. Which of the following statements regarding these neurons is true? A. Very few of these cells die, but their axons do develop sustaining connections in the contralateral superior colliculus. B. Approximately 50% of these cells die during normal development. C. Approximately 85% of these cells die during normal development. D. All of these cells die during normal development. 38. Bcl family members form dimers, some of which promote program cell death in the developing nervous system. Which of the following dimer pairs is likely to be death promoting? A. Bcl-2 : Bax B. Bcl-XL : Bcl-XL C. Bcl-XL : Bax D. Bax : Bax E. More than one of the above are correct. 39. What is a proteolytic target of caspase-9? A. Apaf-1 B. procaspase-3 C. caspase-activated-DNase (CAD) D. CAD inhibitor (ICAD) E. None of the above are correct. 40. Grafting an additional wing bud into the wing bud region of an early developing chick embryo had what effect on subsequent development of the cervical spinal cord? A. increased generation of motor neurons by cell division B. increased survival of motor neurons C. Both of the above are correct. D. None of the above are correct. Class 32 synaptogenesis 41. What neurotransmitter is used by motor neurons to activate skeletal muscles? A. glutamate B. GABA C. acetylcholine D. noradrenalin E. adrenalin 42. Which of the following statements regarding the development of the electrical properties of neurons is true? A. The resting membrane potential of neurons becomes more negative as development progresses. B. The resting membrane potential of neurons becomes more positive as development progresses. C. Voltage-gated sodium channels mediate the first action potentials developmentally, but these channels are lost as other types of voltage-gated channels are expressed. D. The concentration of potassium ions (K+) in the extracellular space of the brain decreases as development progresses. AD E. More than one of the above are correct. Nsci 4100 – Final Exam page 8 43. Which of the following molecules is important for anchoring in place the elements of the active zone of synapses in the CNS? A. neurexins and neuroligins B. PSD95 C. cadherins and protocadherins D. Ig-like cell adhesion molecules (CAMs) AB E. More than one of the above are correct. 44. Which of the following is the receptor for agrin? A. dystroglycan B. rapsyn C. s-laminin D. MuSK E. None of the above are correct. 45. A mutation in the gene for which of the following is likely to result in muscle weakness? A. dystroglycan B. rapsyn C. s-laminin D. MuSK all E. More than one of the above are correct. Class 33 & 34 refinement 46. If you were to keep one eyelid of a kitten continuously closed during its first two months of life, what differences would you expect to find in the brain when the cat is mature compared to a normally reared cat? A. More neurons in the lateral geniculate nucleus would be monocular (i.e. respond to visual activity in one eye and not both eyes). B. More neurons in layer IV of primary visual cortex would be monocular. C. More neurons in layers II and III of primary visual cortex would be monocular. D. More than one of the above are correct. E. None of the above are correct. 47. During development of the nervous system, there are numerous changes in the pattern of axonal connections, a process that we call refinement. These changes include changes in the brain region to which a population of neurons connects and changes in the topography of the connections within a brain region. However, there does not appear to be changes in the laterality of connections (i.e. the side of the body to which a group of neurons connects). True or false? A. true B. false Nsci 4100 – Final Exam page 9 48. The image below shows the electrical potential recorded from an electrode in a developing muscle fiber. The nerve to that muscle was stimulated electrically. Each trace shows the result of stimulating with a different voltage. A higher stimulating voltage resulted in a higher excitatory postsynaptic potential in the muscle fiber. What does this tell you? A. The higher the stimulating voltage, the stronger the action potential in the axon connected that synapses with the muscle fiber. B. The higher the stimulating voltage, the more neurotransmitter was released by the axon at the synapse. C. The higher the stimulating voltage, action potentials were initiated in more axons that connected to the muscle fiber. D. More than one of the above are correct. E. None of the above are correct. 49. Which of the following statements regarding development of ocular dominance columns in visual cortex is true? A. Development of ocular dominance columns requires spontaneous neuronal activity in the retina. B. Development of ocular dominance columns requires spontaneous neuronal activity in the lateral geniculate nucleus. C. Development of ocular dominance columns requires evoked activity in the retina. D. Development of ocular dominance columns does not require neuronal activity outside the cortex. E. None of the above is correct. 50. Which of the following molecules is particularly suited for detecting synchronous activation of multiple synapses on a neuron? A. NMDA glutamate receptors B. AMPA glutamate receptors C. GABAA receptor D. nitric oxide synthase (NOS) 51. Which of the following is NOT involved in refinement of neuronal connections during development? A. elimination of certain synapses B. elimination of certain axonal branches C. addition of certain synapses D. cell death E. All of the above are involved in refinement. Nsci 4100 – Final Exam page 10 52. During refinement of connections in the developing nervous system, studies have suggested that … A. neurotrophin released from a postsynaptic neuron could cause inappropriate synapses to retract. B. neurotrophin released from a postsynaptic neuron could stabilize appropriate synapses. C. nitric oxide released from a postsynaptic neuron could stabilize appropriate synapses. D. NMDA released from a postsynaptic neuron could cause inappropriate synapses to retract AB E. More than one of the above are correct. 53. In developing cerebellum prior to refinement, each purkinje cell receives synapses from … A. multiple granule cells B. multiple climbing fibers C. multiple mossy fibers D. multiple upper (cortical) motor neurons A/B E. More than one of the above are correct. Class 35 behavior 54. The male and female nervous systems are morphologically different in a number of locations. What mechanism is known to account for many of these differences? A. There are a number of genes on the Y chromosome that are expressed in male but not female neurons that result in differences in development of these cells. B. High levels of testosterone from the male gonads (and testosterone derivatives) reduce developmental cell death of certain neurons in the male. C. High levels of testosterone from the male gonads (and testosterone derivatives) increase division of progenitor cells in certain CNS locations. D. High levels of estrogen from the female gonads and other tissues increase developmental cell death of certain neurons in the female. 55. While neuronal activity is required to improve function in many neuronal systems late in development, very early nervous system functions improve independently of neuronal activity. True or false? A. true B. false 56. What mechanism is responsible for the very first movements made by a vertebrate embryo? A. spontaneous activity of myofibers B. spontaneous activity of motor neurons C. spontaneous activity of dorsal root ganglion neurons that synapse with motor neurons D. spontaneous activity of dorsal root ganglion neurons that have transient synapses with myofibers. E. spontaneous activity of neurons in the brain that synapse with motor neurons in the spinal cord. 57. Administering high levels of testosterone systemically to an adult woman would be expected to increase the size of her SDN-POA, but not to the size seen in a normal male brain. True or false? A. true B. false Nsci 4100 – Final Exam page 11 Class 36 research (Georgieff) 58. Iron deficiency during prenatal and early postnatal life can result in … A. motor deficits. B. reduced myelination. C. dendritic abnormalities in cortical neurons particularly in the hippocampus. D. cell migration abnormalities particularly in neocortex. A-C E. More than one of the above are correct. Class 37 disorders 59. A regular dose of which of the following vitamins by a mother during the early stages of pregnancy will significantly reduce the chance of spina bifida in her baby? A. A (retinol) B. B5 (pantothenic acid) C. B9 (folic acid) D. C (ascorbic acid) E. D (cholecalciferol) 60. Fragile-X syndrome has been linked to a trinucleotide repeat in the Fragile-X Mental Retardation gene (FMR1). Which of the following statements is true regarding normal FMR1? A. The gene codes for a microRNA. B. It has an important role in synapse elimination during development. C. The gene codes for Lim kinase. D. The FMR1 protein potentiates the function of Lim kinase. E. More than one of the above are correct. 61. Which of the following developmental maladies is due to a chromosome duplication? A. retinoblastoma B. holoprosencephaly C. Waardenburg syndrome D. Down syndrome E. medulloblastoma 62. A mutation in the patched gene so that the protein cannot interact with smoothened could cause what developmental malady? A. retinoblastoma B. holoprosencephaly C. Waardenburg syndrome D. Down syndrome E. medulloblastoma 63. A mutation in what cell adhesion molecule has been linked to congenital hydrocephalus? A. N-CAM B. N-Cadherin C. L1 D. α2β1 integrin E. ApoER2 Nsci 4100 – Final Exam page 12 Class 38 adult neurogenesis 64. New neurons are added to which of the following brain regions in adult humans? A. CA3 region of the hippocampus B. entorhinal cortex C. olfactory bulb D. striatum E. More than one of the above are correct. 65. Which of the following behaviors has been shown to reduce cell division in the subgranule zone (SGZ)? A. sleep B. exercise C. taking the drug Prozac D. alcohol consumption E. More than one of the above are correct. 66. In an adult rodent or a human, what would be the immediate effect on cells of the subventricular zone (SVZ) after administering a drug that kills dividing cells? A. loss of ependymal cells B. loss of transit amplifying cells C. loss of neural stem cells D. loss of neuroblasts E. More than one of the above are correct. 67. What cell type in the subventricular zone (SVZ) of the mammalian forebrain expresses the transcription factor Sox2 and the intermediate filament protein, nestin? A. ependymal cells B. transit amplifying cells C. neural stem cells D. neuroblasts BC E. More than one of the above are correct. 68. Cell division in the subgranule zone (SGZ) in the adult brain produces neurons that are important for what function? A. sense of smell B. sense of balance and motion C. certain types of learning D. coordination of movement E. More than one of the above are correct. Class 39 injury & regeneration 69. What is believed to trigger the ‘axon reaction’ in a neuron? A. a loss of neurotrophin supply to the soma B. an influx of potassium (K+) into the cell C. an influx of sodium (Na+) into the cell D. free radicals generated by tissue damage E. activation of the ubiquitin system Nsci 4100 – Final Exam page 13 70. If axons in a peripheral nerve are cut, then … A. the cut ends of the axons can rejoin (i.e. fuse back together) as long as the cut is clean and the nerve sheath is intact. B. the nerve will never function again, but neighboring nerves could take over the function of the injured nerve. C. the distal portion of the axons separated from their cell bodies will degenerate, and the portion of the axons still attached to cell bodies will regrow from their cut ends. D. the person is likely to die from nerve hemorrhage. 71. Research has pointed largely to several mechanisms to explain why axon regeneration fails in the adult mammalian central nervous system. Which of the following is NOT one of those mechanisms? A. A glial scar is a barrier to and repels growing axons. B. Molecules in myelin cause growth cones to collapse. C. Molecules that guide growing axons in development are no longer expressed. D. Neurons intrinsically lose the ability to grow an axon at the end of development. 72. Which of the following statements regarding the Nogo receptor (NgR) is NOT true? A. NgR is a receptor tyrosine kinase. B. NgR is a receptor for myelin-associated glycoprotein (MAG) C. Activation of NgR results in activation of RhoA. D. NgR requires LINGO1 to function. 73. While knockout of Nogo or the three Nogo receptor genes did not improve spinal cord regeneration, knockout of p75NTR did allow significant spinal cord regeneration in mice. True or false? A. true B. false Class 40 discussion 74. Misexpressing the transcription factor, Kruppel-like factor-4 (KLF4), in developing cortical neurons in tissue is likely to have what effect on the cells? A. It would reduce the ability of these cells to extend an axon. B. It would increase the speed of axon growth from the cells, and possibly would increase the number of cells with axons. C. It would reduce the migration (movement) of the cells in the culture dish prior to the growth of axons, but should not affect axon growth. D. It would trigger apoptosis, and most of the cells would die. E. It is unlikely that this would affect cell movement or axon growth. Class 41 stem cells 75. Induced pluripotent stem cells (IPSCs) … A. are normally present in many adult tissues in very low abundance. B. are normally present in the umbilical cord. C. can be harvested from the inner cell mass of a blastocyst stage embryo. D. can be harvested from embryos of any stage. E. can be made in the laboratory from differentiated cells. Nsci 4100 – Final Exam page 14 76. Parkinson’s disease begins with the … A. death of pyramidal neurons in the frontal cortex due to too much dopamine. B. death of medium spiny neurons in the striatum due to too much dopamine. C. death of dopaminergic neurons in the striatum of the forebrain. D. death of dopaminergic neurons in the substantia nigra of the midbrain. E. loss of dopamine expression due to a trinucleotide repeat mutation. 77. A major problem with using embryonic stem cells for therapeutic cell replacement is that they are heterogeneous and likely to generate multiple cell type in vivo. True or false? A. true B. false 78. Why are retinal photoreceptor cells an appealing candidate for therapeutic cell replacement following photoreceptor degeneration? A. Photoreceptor cell function is not dependent on receiving information from a presynaptic neuron. B. Photoreceptor axons are not myelinated. C. Photoreceptor axons are myelinated. D. Photoreceptors are part of the peripheral nervous system, which is more amenable to axon growth than the central nervous system. A/B E. More than one of the above are correct. 79. Following a massive stroke in the cerebral cortex, some newly generated neurons have been observed to migrate into the cortex from where? A. Nasal epithelium B. Deep cortical cell layers C. Rostral migratory stream D. Subgranule zone (SGZ) E. Internal capsule Freebie 80. Your professor wishes you a joyous holiday. True or false? A. true B. false The End! Please turn in your bubble answer sheet. You may keep your exam questions. Have a wonderful and safe holiday! …HO, HO, HO!