PhD Transfer Exam
Thursday July 20th, 2017 at 1:10 pm – Ramsay Wright Building, RW 432
Xiao Yu (Takehara-Nishiuchi Lab)
” Prefrontal long-range projection facilitating the formation of temporal association”
The ability to form associations between related events separated in time is important as it allows us to adapt to similar events in the future based on past experiences. I recently found that chemogenetic enhancement of neuron activity in the medial prefrontal cortex (mPFC) enables rats to form stimulus associations over a temporal gap that was prohibitively long for untreated rats to learn. Accompanying this improved learning were ramping increases of theta and beta oscillations in the mPFC during the temporal gap. These findings suggest that mPFC network activity during the gap determines whether two stimuli are associated across the gap. My recent and future work extend this finding in two directions. First, I show that enhancing mPFC activity after learning had no effect on memory formation, suggesting that elevated mPFC activity during learning is critical for memory enhancement. Second, to determine long-range projections through which mPFC activity enhances memory formation, I traced mPFC efferent projections and identified sub regions and cortical layers at which mPFC projections terminate. This, along with past behavioral literature, led me to hypothesize that mPFC projections to the lateral entorhinal cortex (LEC), nucleus reuniens (RE), and mediodorsal thalamus (MD) may be involved in memory enhancement. To test this idea, I will examine the impact of selective chemogenetic activation of the mPFC projections to one of these efferent regions on the formation of temporal associative memories. I will also monitor the activity of mPFC axon terminals in these efferent regions while rats form temporal stimulus associations while learning to ignore irrelevant stimuli. Through these two complementary experiments, I will be able to uncover how the mPFC routes the information on the behavioral relevance of stimuli to specific downstream targets, thereby uncovering a circuit basis on memory regulation by the mPFC.
PhD Transfer Exam
Tuesday June 13th, 2017 at 1:10 pm – Earth Science Building, Room 3087
Artyom Gritsunov (Christendat Lab)
” Structural analysis, kinetic characterization and in vivo investigation of plant quinate dehydrogenases and chlorogenic acid esterases“
The shikimate pathway leads to synthesis of aromatic compounds including lignin, pigments, hormones, and amino acids. Dehydroquinate is an intermediate of the shikimate pathway which can be diverted to other anabolic processes by enzymatic conversion to quinate. In plants, quinate is utilized for biosynthesis of Chlorogenic Acids (CGA). CGAs serve as lignin precursors, antifungal agents, solubility enhancers and UV light protectors. The anabolic aspect of CGA biosynthesis is very well studied, however enzymes involved in the catabolic metabolism of CGAs are poorly characterized. Additionally, the source of quinate remained unknown. To date, we have characterized a family of Quinate Dehydrogenases (QDHs) and identified a family of CGA esterases in a variety of land plants including Solanacea and Brassicaceae species. We hypothesize and aim to test that QDHs in combination with CGA esterases are responsible for regulating the quinate and CGA levels in Solanum species.
PhD Transfer Exam
Thursday, June 8, 2017 at 1:10 pm, CCT-3150, University of Toronto at Mississauga
Ishrat Maliha Islam (Erclik labs)
“ Selective integration of spatial inputs during Drosophila optic lobe neurogenesis”
The Drosophila optic lobe serves as an excellent model system in which to study the mechanisms that regulate neurogenesis. The largest neuropil of the optic lobe, the medulla, is comprised of 40 000 neurons belonging to over 70 neuronal types. These neurons are generated from a single layered epithelial crescent called the outer proliferation center (OPC). Recently, it has been shown that OPC neuroblasts (NB) generate unique sets of neurons based on their temporal state and spatial origin. Surprisingly, NBs that receive identical spatial and temporal inputs can generate both spatially refractory and spatially sensitive neural progeny; uni-columnar neurons are generated by all NBs regardless of spatial origin whereas multi-columnar neurons are generated in spatially restricted domains. For example, despite receiving identical spatial and temporal cues, the two NBs born at the intersection of the Vsx1 spatial and Homothorax (Hth) temporal windows generate distinct neuronal progenies; Pm3s are spatially sensitive multi-columnar neurons while Mi1s are spatially insensitive uni-columnar neurons. This selective integration of spatial inputs during neurogenesis likely serves to control the position and number of neurons that are generated. In this thesis, I propose to address the genetic and molecular mechanisms underlying selective integration within medulla NBs. To date, I have identified that the transcription factor Klumpfuss differentially labels the second Hth NB (but not the first), suggesting that selective integration may occur at the level of the NB itself. I have also found that the transcription factors Rx and Runt are expressed differentially in the Hth1 and Hth2 NB lineages, respectively. During my PhD, I will take advantage of the sophisticated genetic tools available in Drosophila to analyze the lineage relationship of Pm3 and Mi1 neurons. I also propose to utilize transcriptomics and candidate gene approaches to uncover the genetic mechanisms underlying selective integration. Finally, I will characterize the role of Rx and Runt in Hth+ NB lineages. It is anticipated that this research will contribute to our understanding of neurogenesis in both flies and vertebrates where multipotent stem cells also possess the ability to incorporate specific developmental cues to regulate neuronal properties.