Mapping mammalian synaptic connectivity

Yook, Chaehyun; Druckmann, Shaul; Kim, Jinhyun

doi:10.1007/s00018-013-1417-y

Cited by 17 publications

(19 citation statements)

References 82 publications

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“…Furthermore, we did not include every novel tool in each of the categories, as some tools that were developed <5 years ago are already being outperformed by other tools. For more extensive reviews on neuroanatomical tracing, tissue clearing methods, mapping mammalian synaptic connectivity, novel LM imaging techniques, and brain-wide optical tomography techniques, see Lanciego and Wouterlood (2011), Richardson and Lichtman (2015), Yook et al (2013), Eberle et al (2015), and Yuan et al (2015), respectively. Though we did not review older research methods here, we must note that it is important to not immediately discard the older approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Some tools may label synapses by labeling synaptic proteins or by creating chemical reactions in the synaptic cleft (see Figure 1C). Other labels enable the inference of synapses by transsynaptically labeling neurons that are upstream or downstream from a given neuron or neuron population (Yook et al, 2013). …”

Section: Criteria For Evaluating Experimental Methodsmentioning

confidence: 99%

“…First of all, viruses, especially the rabies virus, can be hazardous to laboratory staff, so precautions need to be taken when working with them (Kelly and Strick, 2000). The toxicity of viruses is also an issue; infected tissues die a number of days after performing the injections (Yook et al, 2013). Furthermore, virally-mediated transfections are difficult to direct to a specific location, because viral particles remain viable for hours after injection, and have a tendency to spread through the intercellular brain space.…”

Section: Contemporary Neuroanatomic Research Methodsmentioning

confidence: 99%

“…Some authors have reported false negatives where not all the neurons connected to the target area may be labeled (Yook et al, 2013). Reversely, Beier et al (2011) performed electrophysiological recordings to test the reliability of their transsynaptic viral label and reported synaptic currents in only 5/8 labeled cells.…”

Section: Contemporary Neuroanatomic Research Methodsmentioning

confidence: 99%

“…One of the most important challenges that arises when gathering connectome data is combining data from different scales, each of which is measured by different methods (Sporns, 2013; Yook et al, 2013). EM is best suited for imaging at the subcellular/synaptic scale (Helmstaedter et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions

2016

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Brain networks, localized or brain-wide, exist only at the cellular level, i.e., between specific pre- and post-synaptic neurons, which are connected through functionally diverse synapses located at specific points of their cell membranes. “Connectomics” is the emerging subfield of neuroanatomy explicitly aimed at elucidating the wiring of brain networks with cellular resolution and a quantified accuracy. Such data are indispensable for realistic modeling of brain circuitry and function. A connectomic analysis, therefore, needs to identify and measure the soma, dendrites, axonal path, and branching patterns together with the synapses and gap junctions of the neurons involved in any given brain circuit or network. However, because of the submicron caliber, 3D complexity, and high packing density of most such structures, as well as the fact that axons frequently extend over long distances to make synapses in remote brain regions, creating connectomic maps is technically challenging and requires multi-scale approaches, Such approaches involve the combination of the most sensitive cell labeling and analysis methods available, as well as the development of new ones able to resolve individual cells and synapses with increasing high-throughput. In this review, we provide an overview of recently introduced high-resolution methods, which researchers wanting to enter the field of connectomics may consider. It includes several molecular labeling tools, some of which specifically label synapses, and covers a number of novel imaging tools such as brain clearing protocols and microscopy approaches. Apart from describing the tools, we also provide an assessment of their qualities. The criteria we use assess the qualities that tools need in order to contribute to deciphering the key levels of circuit organization. We conclude with a brief future outlook for neuroanatomic research, computational methods, and network modeling, where we also point out several outstanding issues like structure–function relations and the complexity of neural models.

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Section: Discussionmentioning

confidence: 99%

Section: Criteria For Evaluating Experimental Methodsmentioning

confidence: 99%

Section: Contemporary Neuroanatomic Research Methodsmentioning

confidence: 99%

Section: Contemporary Neuroanatomic Research Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions

2016

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From Cloning Neural Development Genes to Functional Studies in Mice, 30 Years of Advancements

Joyner

2016

Current Topics in Developmental Biology

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Connectomes as constitutively epistemic objects: Critical perspectives on modeling in current neuroanatomy

Haueis

Slaby

2017

Progress in Brain Research

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The term "connectome" is commonly taken to describe a complete map of neural connections in a nervous system of a given species. This chapter provides a critical perspective on the role of connectomes in neuroscientific practice and asks how the connectomic approach fits into a larger context in which network thinking permeates technology, infrastructure, social life, and the economy. In the first part of this chapter, we argue that, seen from the perspective of ongoing research, the notion of connectomes as "complete descriptions" is misguided. Our argument combines Rachel Ankeny's analysis of neuroanatomical wiring diagrams as "descriptive models" with Hans-Jörg Rheinberger's notion of "epistemic objects," i.e., targets of research that are still partially unknown. Combining these aspects we conclude that connectomes are constitutively epistemic objects: there just is no way to turn them into permanent and complete technical standards because the possibilities to map connection properties under different modeling assumptions are potentially inexhaustible. In the second part of the chapter, we use this understanding of connectomes as constitutively epistemic objects in order to critically assess the historical and political dimensions of current neuroscientific research. We argue that connectomics shows how the notion of the "brain as a network" has become the dominant metaphor of contemporary brain research. We further point out that this metaphor shares (potentially problematic) affinities to the form of contemporary "network societies." We close by pointing out how the relation between connectomes and networks in society could be used in a more fruitful manner.

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Mapping mammalian synaptic connectivity

Cited by 17 publications

References 82 publications

Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions

Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions

From Cloning Neural Development Genes to Functional Studies in Mice, 30 Years of Advancements

Connectomes as constitutively epistemic objects: Critical perspectives on modeling in current neuroanatomy

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