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 cellular diversity and hippocampal processing in health and disease. We used in vitro electrophysiology combined with optogenetics to study active and passive properties and connectivity in the subiculum, prefrontal cortex and retrosplenial cortex. In summary, in Chapter 3 we characterize the projection from the dorsal subiculum (dSUB) to the medial prefrontal cortex (mPFC) in detail. We show that the dSUB mainly projects to the dorsal regions of the mPFC. The projection was stronger more posterior in the mPFC compared to the anterior mPFC, showing maximal projection to the dorsal and ventral anterior cingulate cortex (ACC). In terms of cell-type specificity, the dSUB projects to both excitatory and inhibitory neurons in the mPFC, apart from neurogliaform cells. In Chapter 4 we continue to investigate the dSUB but in relation to depression. We show that maternal separation of pups results in mild depressivelike behaviour and that adult mice can be subsequently grouped in resilient and susceptible to the early-life stress. The main findings from this chapter are an increase in acute stress-induced activation of dSUB neurons and an increase in the 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 the RSC following maternal separation. Chapter 5 investigates differences in NPY-positive neurons between the cortex and hippocampus. This study provides a proof of concept to investigate electrophysiological and gene expression differences between brain regions for specific cell types and to validate these using pharmacology. The example used in this chapter reveals differences in gene expression between the auditory cortex and CA3 NPY-positive neurons, which is potentially related to the differential developmental origin of interneurons in these brain regions. Whereas it is thought that transcriptomically-defined inhibitory cell types are largely similar across brain regions, this research challenges that idea, at least for NPY-positive interneurons. To conclude, this thesis stresses the point that accurate cell type classification is essential for improvement of cell-type specific investigations, which provides more insight into the pathology of disorders on a cellular and circuitry level. Subsequently, this could lead to a better understand of various brain disorders and potentially discover targets for more selective and specific treatments.
- Advisor / supervisor
- Wozny, Christian
- Resource Type
- Note
- Previously held under moratorium from 26 January 2023 until 26 January 2024.
- DOI
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