مورد إلكتروني
Novel molecular tools for cellular- and subcellular-targeting of neuronal transgene expression
| العنوان: | Novel molecular tools for cellular- and subcellular-targeting of neuronal transgene expression |
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| بيانات النشر: | 2021 |
| تفاصيل مُضافة: | Wykes, Alexander David |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Among the questions addressed by modern neuroscience is how distinct cellular structures within the nervous system give rise to particular behaviours and cognitive functions. Our ability to address such questions has been greatly enhanced with the emergence of ‘transgenic’ technologies, which allow the introduction of foreign or engineered genes into biological systems of interest, such as neural circuits. This capacity to introduce and express transgenes in neurons has led to the development of a diverse catalogue of genetically encoded markers, sensors, and actuators, which provide powerful insights into the structure and function of the nervous system. In addition to their intrinsic utility, mechanisms exist by which expression of these transgenic tools can be selectively directed to cell-types and subcellular structures of interest. Studies described in this thesis sought to establish new molecular tools and approaches for localised transgene expression in neural structures of scientific and therapeutic importance. Transgene delivery to neural circuits of interest was mediated here in rats using viral vectors, particularly adeno-associated viral (AAV) vectors, from which targeted transduction of neurons expressing the highly conserved neuropeptide, relaxin-3, was achieved using a novel cell-type specific promoter. Relaxin-3 is most abundantly expressed by a subpopulation of neurons in the pontine nucleus incertus (NI) and has been identified as an important modulator of arousal and other interrelated cognitive functions and behaviours, making the relaxin-3 system a promising therapeutic target. To better understand this circuitry using transgenic approaches, I sought to identify a promoter sequence capable of regulating cell-type specific transgene expression in relaxin-3 neurons. In parallel to a relaxin-3 promoter sequence (1,736 bp), I also characterised transgene expression under an 880 bp tropomyosin receptor kinase A (TrkA) promoter, as TrkA is exclusively |
| مصطلحات الفهرس: | Adeno-associated viral (AAV) vector, Amygdala, Axon, Soma, Cardiorespiratory coupling, Cell-type specific promoter, Central autonomic network, GtACR2, Kv2.1, Neurexin, Neuroscience, Nucleus incertus (NI), Nucleus of the solitary tract (NST), Optogenetics, PreBötzinger complex, Subcellular trafficking, Transgene, PhD thesis |
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| أرقام أخرى: | UMV oai:jupiter.its.unimelb.edu.au:11343/281905 1315691194 |
| المصدر المساهم: | UNIV OF MELBOURNE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1315691194 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |