Two-Photon Optogenetic Mapping of Excitatory Synaptic Connectivity and Strength

Izquierdo-Serra, Mercè; Hirtz, Jan J.; Shababo, Ben; Yuste, Rafael

doi:10.1016/j.isci.2018.09.008

Cited by 24 publications

(20 citation statements)

References 46 publications

(58 reference statements)

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“…Patch-clamp recordings can furthermore be combined with presynaptic stimulation using extracellular electrodes, channelrhodopsin or glutamate uncaging to further map synaptic inputs from more neurons. Stimulation through a high-density multielectrode array or two-photon glutamate uncaging allows mapping of monosynaptic inputs from 10 to 50 presynaptic neurons onto a single patched neuron (Fino and Yuste, 2011; Jäckel et al, 2017), while two-photon optogenetic stimulation can probe connections from up to 200 presynaptic neurons in a single experiment (Izquierdo-Serra et al, 2018). These approaches do not resolve electrophysiological and anatomical properties and further connectivity of the presynaptic neurons, but they can be used to complement the multipatch approach.…”

Section: Discussionmentioning

confidence: 99%

High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp

Peng

Mittermaier

Planert

et al. 2019

eLife

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Comparing neuronal microcircuits across different brain regions, species and individuals can reveal common and divergent principles of network computation. Simultaneous patch-clamp recordings from multiple neurons offer the highest temporal and subthreshold resolution to analyse local synaptic connectivity. However, its establishment is technically complex and the experimental performance is limited by high failure rates, long experimental times and small sample sizes. We introduce an in vitro multipatch setup with an automated pipette pressure and cleaning system facilitating recordings of up to 10 neurons simultaneously and sequential patching of additional neurons. We present hardware and software solutions that increase the usability, speed and data throughput of multipatch experiments which allowed probing of 150 synaptic connections between 17 neurons in one human cortical slice and screening of over 600 connections in tissue from a single patient. This method will facilitate the systematic analysis of microcircuits and allow unprecedented assessment of inter-individual variability.

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Section: Discussionmentioning

confidence: 99%

High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp

Peng

Mittermaier

Planert

et al. 2019

eLife

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“…Absent further information it is assumed here that all signal velocities over links are constant. The analysis also needs estimates of synaptic delay for multi-hop signal paths, here taken as 2 ms [89], which can be taken as equivalent to a 2 mm additional path length. Thus link length (mm) can be taken as a proxy for signal delay over that link (in msec).…”

Section: Temporal Networkmentioning

confidence: 99%

Network analysis of mesoscale mouse brain structural connectome yields modular structure that aligns with anatomical regions and sensory pathways

Pailthorpe

2019

Preprint

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The Allen mesoscale mouse brain structural connectome is analysed using standard network methods combined with 3D visualizations. The full region-to-region connectivity data is used, with a focus on the strongest (top 40%) structural links. The spatial embedding of links and time evolution of signalling is incorporated, with twostep links included. Modular decomposition using the Infomap method produces 8 network modules that correspond approximately to major brain anatomical regions and system functions. These modules align with the anterior and posterior primary sensory systems and association areas. 3D visualization of network links is facilitated by using a set of simplified schematic coordinates that reduces visual complexity. Selection of key nodes and links, with a focus on primary sensory pathways and cortical association areas, together reveal structural features of the mouse structural connectome consistent with biological functions in the sensory-motor systems, and selective roles of the anterior and posterior cortical association areas of the mouse brain. The fabric of weaker links generally are longer range with some having brainwide reach. Cortical gradients are evident along sensory pathways within the structural network. Author's SummaryNetwork models incorporating spatial embedding and signalling delays are used to investigate the mouse structural connectome. Here computational method work like experimental probes to uncover biologically relevant features. I use the Infomap method, which follows random walks on the network, to decompose the directed, weighted network into 8 modules that align with classical brain anatomical regions and system functions. Primary sensory pathways and cortical association areas are separated into individual modules. Strong, short range links form the sensory-motor paths while weaker links spread brain-wide, possibly coordinating many regions. modern experimental probes (e.g. see [8]). The challenge is to find appropriate network models that can realistically reproduced/predict brain structural and functional connectivity data.Here the Allen Institute for Brain Science (AIBS) dataset of a mesoscale structural connectome for the mouse brain [9] is studied using a combination of data analytical, network and visualization methods. While the data is brain wide it is at the meoscale (resolution of 0.1 mm voxels and 0.35 mm coronal plane imaging), in which links involving many neurons are probed. Connectivity data at finer scales, at the level of individual neurons and synapses, are available for smaller samples, such as with mouse retina [10,11]. Higher resolution data also is emerging at the level of cortical layers [14]. These studies shed light on the correlation between structural and functional connections between nodes in the mouse brain. The nodes are located at known 3D coordinates from the Allen Atlas [13]. Typically the sources and targets of the probed connections are classical anatomical regions that, given sampling protocols, vary significantly in size and fu...

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“…Another study also presented a conventional optogenetic two-photon mapping method in mouse neocortical slices by activating pyramidal cells with the red-shifted opsin C1V1, while recording postsynaptic responses in whole-cell configuration. The use of temporal-focused excitation or holographic stimulation, as in earlier method, limits the problem of dendritic activation, yet the current method is simple and fast [182].…”

Section: Optical Transfection/optogeneticsmentioning

confidence: 99%

A Single-Neuron: Current Trends and Future Prospects

Gupta

Balasubramaniam

Chang

et al. 2020

Cells

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The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas. The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features. In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity. This review highlights various single-neuron models and their behaviors, followed by different analysis methods. Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in detail the role of single-neuron mapping and electrophysiological recording. We also elaborate on the recent development of single-neuron isolation, manipulation, and therapeutic progress using advanced micro/nanofluidic devices, as well as microinjection, electroporation, microelectrode array, optical transfection, optogenetic techniques. Further, the development in the field of artificial intelligence in relation to single-neurons is highlighted. The review concludes with between limitations and future prospects of single-neuron analyses.

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Two-Photon Optogenetic Mapping of Excitatory Synaptic Connectivity and Strength

Cited by 24 publications

References 46 publications

High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp

High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp

Network analysis of mesoscale mouse brain structural connectome yields modular structure that aligns with anatomical regions and sensory pathways

A Single-Neuron: Current Trends and Future Prospects

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