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Front. Neurosci. | doi: 10.3389/fnins.2019.00897

A student’s guide to neural circuit tracing

  • 1Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Australia
  • 2Université Paris-Saclay, France
  • 3Olympus Australia Pty. Ltd., Australia

The mammalian nervous system is comprised of a seemingly infinitely complex network of specialised synaptic connections that coordinate the flow of information through it. The field of connectomics seeks to map the structure that underlies brain function at resolutions that range from the ultrastructural, which examines the organisation of individual synapses that impinge upon a neuron, to the macroscopic, which examines gross connectivity between large brain regions. At the mesoscopic level, distant and local connections between neuronal populations are identified, providing insights into circuit-level architecture.
Although neural tract tracing techniques have been available to experimental neuroscientists for many decades, considerable methodological advances have been made in the last twenty years due to synergies between the fields of molecular biology, virology, microscopy, computer science and genetics. As a consequence, investigators now enjoy an unprecedented toolbox of reagents that can be directed against selected subpopulations of neurons to identify their efferent and afferent connectomes. Unfortunately, the intersectional nature of this progress presents newcomers to the field with a daunting array of technologies that have emerged from disciplines they may not be familiar with. This review outlines the current state of mesoscale connectomic approaches, from data collection to analysis, written for the novice to this field. A brief history of neuroanatomy is followed by an assessment of the techniques used by contemporary neuroscientists to resolve mesoscale organisation, such as conventional and viral tracers, and methods of selecting for sub-populations of neurons. We consider some weaknesses and bottlenecks of the most widely used approaches for the analysis and dissemination of tracing data and explore the trajectories that rapidly developing neuroanatomy technologies are likely to take.

Keywords: Neuroanatomy, Viral tracers, Anterograde Tracer, retrograde tracers, synaptic contacts, Connectome Analysis

Received: 31 May 2019; Accepted: 12 Aug 2019.

Edited by:

Vaughan G. Macefield, Baker Heart and Diabetes Institute, Australia

Reviewed by:

Eberhard Weihe, University of Marburg, Germany
Patrice G. Guyenet, University of Virginia, United States
Alice McGovern, The University of Melbourne, Australia  

Copyright: © 2019 Saleeba, Dempsey, Le, Goodchild and McMullan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Simon McMullan, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Sydney, NSW 2109, Australia,