Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility

Aimee Bertolli; Oday Halhouli; Matthew A Weber; Yiming Liu-Martínez; Linder H Wendt; Brianna Blaine; Ramasamy Thangavel; Sura Smadi; Preston J Pellatz; Danlin Liu; Kaisa N Bornhoft; Kalpana Gupta; Riley Dean; Margaret M Tish; Gemma Kerr; Shane A Heiney; Eric B Emmons; Qiang Zhang; Serena B Gumusoglu; Nandakumar S Narayanan; Joel C Geerling; Georgina M Aldridge

doi:10.1016/j.ymeth.2026.04.004

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Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility

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Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility

Aimee Bertolli, Oday Halhouli, Matthew A Weber, Yiming Liu-Martínez, Linder H Wendt, Brianna Blaine, Ramasamy Thangavel, Sura Smadi, Preston J Pellatz, Danlin Liu, …

Methods (San Diego, Calif.), Vol.251, pp.64-82

07/2026

DOI: 10.1016/j.ymeth.2026.04.004

PMID: 41966430

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Abstract

Land-based spatial mazes are a low-stress method to evaluate learning in rodent models of dementia. By using innate exploratory and hiding behavior, the Barnes maze requires fewer trials, allowing examination of early learning rate and retention, as well as executive and motivational features that can be characteristic of non-amnestic dementias. However, unwanted odor cues may disrupt interpretation of acquisition rate during typical learning trials. We designed and tested our Barnes FIELD protocol (Find the Invisible Exit to Locate the Domicile) to improve reproducibility, allow evaluation of learning trials, and limit experimenter influence. The protocol uses 3D-printed escape shuttles and docking tunnels, allowing mice to exit the maze to the home cage. We show evidence that our shuttles mitigate the possibility of undesired cues. We demonstrate the feasibility of our protocol across several models of cognitive impairment and aging, and develop an additional stage, the STARR (Spatial Training And Rapid Reversal) maze, to better challenge behavioral flexibility. By examining commonly used outcome measures we identify important considerations for interpretation. These insights are used to evaluate several models of cognitive change, including deficits in an Alzheimer's disease mouse model and behavioral flexibility in a model of brainstem dysfunction. This work provides comprehensive instructions to build, perform, and analyze a robust spatial maze that expands the range of behavioral and motivational outcomes that can be identified and screened. Our findings will aid interpretation of traditional protocols, enhance rigor and reproducibility, and provide an updated method to screen for cognitive changes in mice.

Aging

Traumatic Brain Injury

Executive function

Behavioral flexibility

Perseveration

Neurodegeneration

Perseverance

Long term memory

Normal pressure hydrocephalus

Barnes maze

Radial arm

Working memory

Short term memory

Details

Title: Subtitle: Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility
Creators: Aimee Bertolli - University of Iowa
Oday Halhouli - University of Iowa
Matthew A Weber - University of Iowa
Yiming Liu-Martínez - University of Iowa
Linder H Wendt - Southern California Clinical and Translational Science Institute
Brianna Blaine - University of Iowa
Ramasamy Thangavel - University of Iowa
Sura Smadi - University of Iowa
Preston J Pellatz - University of Iowa
Danlin Liu - University of Iowa
Kaisa N Bornhoft - University of Iowa
Kalpana Gupta - University of Iowa
Riley Dean - University of Iowa
Margaret M Tish - University of Iowa
Gemma Kerr - University of Iowa
Shane A Heiney - Neurosciences Institute
Eric B Emmons - Drake University
Qiang Zhang - University of Iowa
Serena B Gumusoglu - University of Iowa
Nandakumar S Narayanan - University of Iowa
Joel C Geerling - University of Iowa
Georgina M Aldridge - University of Iowa
Resource Type: Journal article
Publication Details: Methods (San Diego, Calif.), Vol.251, pp.64-82
DOI: 10.1016/j.ymeth.2026.04.004
PMID: 41966430
NLM abbreviation: Methods
ISSN: 1095-9130
eISSN: 1095-9130
Publisher: Elsevier
Grant note: NIH: NINDS NS129711, NINDS NS134833 SMASH Dementia Research Program of Excellence from the Roy J. Carver Charitable Trust University of Iowa Medical Scientist Training Program STEAD family Scholarship: UM1TR004403 National Center For Advancing Translational Sciences of the National Institutes of Health: UM1TR004403 Hydrocephalus Association 2019 Innovator Award: NS116947 Iowa Fraternal Order of Eagles Alzheimer's and Neurological Fund NINDS: NS116947
This work was supported by NIH RO1s: NINDS NS129711, NINDS NS134833, the SMASH Dementia Research Program of Excellence from the Roy J. Carver Charitable Trust, the University of Iowa Medical Scientist Training Program, and the STEAD family Scholarship to GMA, and the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UM1TR004403. Hydrocephalus Association 2019 Innovator Award to JCG. Iowa Fraternal Order of Eagles Alzheimer's and Neurological Fund to JCG. NINDS F31/NRSA award NS116947 to MMT.
Language: English
Electronic publication date: 04/09/2026
Date published: 07/2026
Academic Unit: Neurology; Psychiatry; Iowa Neuroscience Institute; Surgery; Obstetrics and Gynecology; Neuroscience and Pharmacology
Record Identifier: 9985152243302771

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