Beyond the Basics: Experimental Design in Neuroscience

The notion of an experiment is so simple that we teach the basics in elementary school: randomly assign to treatment or control groups, then see what happens. This apparent simplicity belies important complexities. For example: (1) how, exactly, should randomization be accomplished?, (2) with complex procedures involving levels of analysis (animals to slices to cells), what ends up counting as a sample size?, and (3) how can important nuisance factors like cage effects be accounted for?

Published in eNeuro, two tutorials by Reynolds guide readers beyond the basics when designing experiments in neuroscience. The first¹ provides a clear, concise foundation, explaining the key concepts and terminology while teaching how to avoid common pitfalls like psudoreplication and inadequate randomization. The second paper² gives a practical guide to blocking, the strategy of systematically accounting for nuisance variables from design through to analysis. Blocking helps reduce within-group variation, providing more efficient and powerful experiments that provide clearer answers with less resources.

Reynolds’ guides include clear examples from neuroscience, references you’ll be scrambling to read, and sample code that you can adapt to create and analyze your own sophisticated, efficient experiments. These guides should provide an outstanding resource for trainees and will likely provide even the most seasoned of researchers with some useful food for thought.

These two new papers on experimental design further extend eNeuro’s “Improving Your Neuroscience” series, with other recent pieces providing guides to analyzing nonnormal data (Malek-Ahmadi et al., 2026), avoiding confirmation bias (Born, 2024), simulating data to sharpen statistical thinking (Rousselet, 2025), and teaching experimental rigor (Tan and Li, 2025).

If you have a suggestion for additional topics or want to propose contributing a piece please email the eNeuro advisory board member Robert Calin-Jageman (rcalinjageman@dom.edu) or leave a comment below.  

Read the Commentaries:

• ¹Experimental Designs for Preclinical Neuroscience Experiments: Part I—Design Basics
• ²Experimental Designs for Preclinical Neuroscience Experiments: Part 2—Blocking and Blocked Designs

Browse Improving Your Neuroscience: a collection of articles aimed at providing accessible, practical, authoritative tutorials for neuroscientists.