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Integrated circuit analysis of the mouse visual system
Integrated circuit analysis of the mouse visual system
Neocortical pyramidal cells (PCs) display functional specializations defined by their connectivity as well as their molecular, anatomical and electrophysiological properties. For layer 2/3 (L2/3) PCs little is known about the detailed relationship between their neuronal response properties and their underlying cellular properties as well as their circuit connectivity. The first part of this thesis characterizes the morphological and electrophysiological properties of L2/3 PCs in the binocular zone of mouse primary visual cortex (V1) to reveal potential L2/3 PC subtypes. Analysis based on electrophysiology and morphology argues against morpho-electrophysiological L2/3 PC subtypes in mouse V1. The second part of this thesis investigates whether L2/3 PCs differ in their connectivity patterns and whether this is related to differences in their stimulus preferences. Laser scanning photostimulation (LSPS) by UV glutamate uncaging in brain slices reveals that L2/3 PCs receive to varying degrees excitatory input from L2/3 and L5 in addition to the canonical L4 input and that the sources of excitatory and inhibitory input are not balanced in all cells. In order to probe the functional implications of the different input patterns this study presents an in vivo / in vitro approach: First, the visual response properties (orientation/direction selectivity, temporal/spatial preferences, ocular dominance and spontaneous activity) of individual L2/3 PCs expressing a genetically encoded calcium indicator (GECI) are characterized with in vivo 2-photon calcium imaging. Subsequently, the very same neurons are re-identified in brain slices for circuit analysis with LSPS. Therefore, this study is able to directly relate the functional response properties of neurons to the underlying laminar excitatory and inhibitory inputs for the first time. Analyses of the relation between functional response properties measured in vivo and the laminar connectivity assessed in vitro do not reveal distinct subtypes of L2/3 PCs embedded in functional microcircuits in accordance with the morphological and electrophysiological observations. Therefore, the diversity of visual response properties of neighbouring L2/3 PCs in mouse visual cortex is not directly related to their laminar connectivity. The last part of this thesis challenges the classical view of strict eye-specific information segregation within the adult dorsolateral geniculate nucleus (dLGN). Thalamic cells (TCs) have been demonstrated to display binocular responses at the level of the dLGN in the adult animal, but the underlying circuit has not been investigated. This thesis develops a dual-color optogenetic approach enabling eye-specific retinal input mapping onto single TCs. The application of this dual-color photostimulation approach provides the first evidence of binocularity at the level of the retinogeniculate synapse.
In vivo/in vitro, calcium imaging, in vivo 2-photon imaging, patch-clamp, genetically encoded calcium indicator, sensory cortex, visual cortex, laser-scanning photostimulation, synaptic connectivity, dLGN, dual optogenetic circuit mapping, retinogeniculate synapse
Weiler, Simon
2018
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Weiler, Simon (2018): Integrated circuit analysis of the mouse visual system. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)
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Abstract

Neocortical pyramidal cells (PCs) display functional specializations defined by their connectivity as well as their molecular, anatomical and electrophysiological properties. For layer 2/3 (L2/3) PCs little is known about the detailed relationship between their neuronal response properties and their underlying cellular properties as well as their circuit connectivity. The first part of this thesis characterizes the morphological and electrophysiological properties of L2/3 PCs in the binocular zone of mouse primary visual cortex (V1) to reveal potential L2/3 PC subtypes. Analysis based on electrophysiology and morphology argues against morpho-electrophysiological L2/3 PC subtypes in mouse V1. The second part of this thesis investigates whether L2/3 PCs differ in their connectivity patterns and whether this is related to differences in their stimulus preferences. Laser scanning photostimulation (LSPS) by UV glutamate uncaging in brain slices reveals that L2/3 PCs receive to varying degrees excitatory input from L2/3 and L5 in addition to the canonical L4 input and that the sources of excitatory and inhibitory input are not balanced in all cells. In order to probe the functional implications of the different input patterns this study presents an in vivo / in vitro approach: First, the visual response properties (orientation/direction selectivity, temporal/spatial preferences, ocular dominance and spontaneous activity) of individual L2/3 PCs expressing a genetically encoded calcium indicator (GECI) are characterized with in vivo 2-photon calcium imaging. Subsequently, the very same neurons are re-identified in brain slices for circuit analysis with LSPS. Therefore, this study is able to directly relate the functional response properties of neurons to the underlying laminar excitatory and inhibitory inputs for the first time. Analyses of the relation between functional response properties measured in vivo and the laminar connectivity assessed in vitro do not reveal distinct subtypes of L2/3 PCs embedded in functional microcircuits in accordance with the morphological and electrophysiological observations. Therefore, the diversity of visual response properties of neighbouring L2/3 PCs in mouse visual cortex is not directly related to their laminar connectivity. The last part of this thesis challenges the classical view of strict eye-specific information segregation within the adult dorsolateral geniculate nucleus (dLGN). Thalamic cells (TCs) have been demonstrated to display binocular responses at the level of the dLGN in the adult animal, but the underlying circuit has not been investigated. This thesis develops a dual-color optogenetic approach enabling eye-specific retinal input mapping onto single TCs. The application of this dual-color photostimulation approach provides the first evidence of binocularity at the level of the retinogeniculate synapse.