The Head-fixed Behaving Rat--procedures and Pitfalls
Overview
Authors
Affiliations
This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models--the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging.
Magnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons.
Rich P, Thiberge S, Scott B, Guo C, Tervo D, Brody C Nat Commun. 2024; 15(1):4154.
PMID: 38755205 PMC: 11099169. DOI: 10.1038/s41467-024-48505-9.
Advances in cellular resolution microscopy for brain imaging in rats.
Kim S, Affan R, Frostig H, Scott B, Alexander A Neurophotonics. 2023; 10(4):044304.
PMID: 38076724 PMC: 10704261. DOI: 10.1117/1.NPh.10.4.044304.
Deep-brain optical recording of neural dynamics during behavior.
Zhou Z, Gordon-Fennell A, Piantadosi S, Ji N, Smith S, Bruchas M Neuron. 2023; 111(23):3716-3738.
PMID: 37804833 PMC: 10843303. DOI: 10.1016/j.neuron.2023.09.006.
Activity in Barrel Cortex Related to Trace Eyeblink Conditioning.
Silva-Prieto M, Hofmann J, Schwarz C eNeuro. 2023; 10(8).
PMID: 37553241 PMC: 10449485. DOI: 10.1523/ENEURO.0206-23.2023.
Opto-juxtacellular interrogation of neural circuits in freely moving mice.
Ding L, Balsamo G, Diamantaki M, Preston-Ferrer P, Burgalossi A Nat Protoc. 2023; 18(8):2415-2440.
PMID: 37420087 DOI: 10.1038/s41596-023-00842-7.