Thesis
Behavioural, electrophysiological and pharmacological investigations on cell type-specific neural processing in different cortical and hippocampal brain regions
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2022
- Thesis identifier
- T16472
- Person Identifier (Local)
- 201879667
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- In this thesis, three different projects are presented that are centred on cellulardiversity and hippocampal processing in health and disease. We used in vitroelectrophysiology combined with optogenetics to study active and passiveproperties and connectivity in the subiculum, prefrontal cortex and retrosplenialcortex. In summary, in Chapter 3 we characterize the projection from the dorsalsubiculum (dSUB) to the medial prefrontal cortex (mPFC) in detail. We show thatthe dSUB mainly projects to the dorsal regions of the mPFC. The projection wasstronger more posterior in the mPFC compared to the anterior mPFC, showingmaximal projection to the dorsal and ventral anterior cingulate cortex (ACC). Interms of cell-type specificity, the dSUB projects to both excitatory and inhibitoryneurons in the mPFC, apart from neurogliaform cells.In Chapter 4 we continue to investigate the dSUB but in relation todepression. We show that maternal separation of pups results in mild depressivelike behaviour and that adult mice can be subsequently grouped in resilient andsusceptible to the early-life stress. The main findings from this chapter are anincrease in acute stress-induced activation of dSUB neurons and an increase inthe excitatory drive onto fast-spiking interneurons in the retrosplenial cortex (RSC)from the dSUB that may lead to a strengthening of the feedforward inhibition in theRSC following maternal separation.Chapter 5 investigates differences in NPY-positive neurons between thecortex and hippocampus. This study provides a proof of concept to investigateelectrophysiological and gene expression differences between brain regions forspecific cell types and to validate these using pharmacology. The example used inthis chapter reveals differences in gene expression between the auditory cortexand CA3 NPY-positive neurons, which is potentially related to the differentialdevelopmental origin of interneurons in these brain regions. Whereas it is thoughtthat transcriptomically-defined inhibitory cell types are largely similar across brainregions, this research challenges that idea, at least for NPY-positive interneurons.To conclude, this thesis stresses the point that accurate cell typeclassification is essential for improvement of cell-type specific investigations, whichprovides more insight into the pathology of disorders on a cellular and circuitrylevel. Subsequently, this could lead to a better understand of various braindisorders and potentially discover targets for more selective and specifictreatments.
- Advisor / supervisor
- Wozny, Christian
- Resource Type
- Note
- Previously held under moratorium from 26 January 2023 until 26 January 2024.
- DOI
关系
项目
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PDF of thesis T16472 | 2023-02-14 | 公开 | 下载 |