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Lecture 1 of the connectomics lecture series. 59 slides in three parts, about 150 minutes. Openly licensed — CC BY-SA 4.0.

What this lecture covers

Why synapse-resolution structure needs electron microscopy, what a wiring diagram can and cannot establish, the three scales, and the state of the field through 2025.

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Learning objectives

By the end of this lecture, participants will be able to:

  1. Explain why synapse-resolution structure requires electron microscopy, using the resolution and data-volume arithmetic.
  2. Differentiate acquisition, reconstruction, and analysis scale for a stated research question.
  3. Classify a connectivity claim as supported by structure alone, by structure plus a declared assumption, or not by structure.
  4. Communicate the current challenges and opportunities in connectomics without overclaiming.

Structure

Part A — The case for mapping

The resolution argument in numbers, the cost argument you can do in your head, and the three bins every connectivity claim falls into.

Part B — Three scales that are not the same thing

Acquisition, reconstruction, and analysis scale; the modality chart and the tradeoff triangle; representations, registration, and scale leakage.

Part C — The field as it stands

Forty years of milestones tagged by stream, the landmark datasets and what each actually delivered, open problems, and how to read a connectomics paper.

What students produce

A one-page study brief on a question the student cares about: a measurable endpoint with units, a null model stated in words, and an explicit non-claim.

The centrepiece

The claim-sorting framework in Part A. It is introduced here, used in every subsequent lecture, and is what the lecture 3 lab is graded against. Students routinely treat lecture 1 as background and skip to the tools; it is worth saying out loud that this part is load-bearing.

Notes for whoever teaches it

The cold open pays off eleven slides later. Three claims about the same circuit are put to the room early and deliberately left unresolved. Take a show of hands on each — most rooms accept the first, split on the second, and about a third accept the third because it sounds like something they have read. That last group is the point of the exercise.

Part A ends on a constructive turn, not a limitation. Students hear “structure cannot establish this” as “connectomics cannot do anything interesting”. The right reading is that it tells you exactly which additional experiment your question needs. MICrONS exists because someone decided to co-register two-photon physiology with the EM volume.

The decision rule dislodges a common instinct. Learners arrive assuming nanoscale is the serious scale. The rule is the coarsest acquisition scale that resolves the analysis unit — choosing EM when light microscopy answers the question is a five-order-of-magnitude error, not caution.

Licence and credit

CC BY-SA 4.0. Teach from this lecture anywhere, including commercially; copy and redistribute it in any medium; and re-cut, shorten, translate, or merge it into your own material. No permission needed. Two conditions: credit the original and say if you changed anything, and distribute your adapted version under the same licence.

Gray Roncal, W. (2026). Introduction to Connectomics (EN.585.781 Frontiers in Neuroengineering, Module 7). NeuroTrailblazers. CC BY-SA 4.0. https://neurotrailblazers.org/teaching/lectures/

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