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Characterizations of the Whole Cortical Column Cellular Responses to Microbleeds and Neuroelectronic Devices

Yang, Qianru (2023) Characterizations of the Whole Cortical Column Cellular Responses to Microbleeds and Neuroelectronic Devices. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Neuroelectronic devices play a crucial role in neuroscience research, diagnosis, treatment of neurological disorders, neuro-prosthetics, and brain-computer interfaces. However, the cellular mechanisms involved in recording and stimulation are not fully understood. Two-photon microscopy (TPM) has been an elegant tool to investigate cellular activity in vivo, but its imaging depth is often limited to the superficial cortex, especially in chronic studies. Microprisms offer a unique advantage by providing a vertical imaging plane to study neural circuits across cortical layers. However, the potential of microprism implantation in neuroelectronic interface studies has not been demonstrated, and the extent of tissue damage caused by chronic microprism implantation remains unclear.
This dissertation aims to establish the usage of microprism implantation for studying neural electronic interfaces in vivo. Firstly, it presents a traditional TPM way of visualizing inflammatory responses to neural electrodes implanted in the superficial cortex. Secondly, it characterizes the chronic inflammatory responses to microprism implantation in the brains of living mice. The results show that inflammatory responses can return to a homeostatic state after several weeks of recovery, laying the groundwork for investigating inflammation-related cellular activities using microprisms. Thirdly, the dissertation examines the dynamic changes of microglia and neural networks following a focal blood vessel injury using chronic microprism implantations in awake mice. This part reveals functional connectivity changes in cortical neuron circuits and alterations in microglia-neuron interactions that occur after cortical microbleeds. These findings provide valuable insights for future inventions and treatments in this area. Lastly, the dissertation develops a novel device that integrates microprisms with a microelectrode array (MEA), enabling simultaneous 2P imaging and electrophysiology recording/stimulation across cortical layers. Leveraging this device, the dissertation visualizes how microstimulation parameters influence neural circuit activity throughout the cortical column in vivo.
Overall, this dissertation establishes a revolutionized in vivo imaging platform for studying neuroelectronic interfaces and provides novel insights into the cellular mechanisms of intracortical neural implants, contributing to advancing the field of neuroelectronic interfaces and our understanding of their cellular mechanisms.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Yang, Qianruqiy24@pitt.eduqiy240000-0003-4245-6631
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCui, Tracy Xinyanxic11@pitt.eduxic11
Committee MemberVazquez, Alberto L.alv15@pitt.edualv15
Committee MemberGaunt, Robertrag53@pitt.edurag53
Committee MemberHu,
Date: 14 September 2023
Date Type: Publication
Defense Date: 18 May 2023
Approval Date: 14 September 2023
Submission Date: 10 July 2023
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 199
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Two-photon microscopy, microprism, brain-machine interface, calcium imaging, neuroinflammation
Date Deposited: 14 Sep 2023 13:42
Last Modified: 14 Sep 2023 13:42


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