Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain

Miriam E Bocarsly; Wan-Chen Jiang; Chen Wang; Joshua T Dudman; Na Ji; Yeka Aponte

doi:10.1364/BOE.6.004546

Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain

Biomed Opt Express. 2015 Oct 23;6(11):4546-56. doi: 10.1364/BOE.6.004546. eCollection 2015 Nov 1.

Authors

Miriam E Bocarsly¹, Wan-Chen Jiang², Chen Wang³, Joshua T Dudman³, Na Ji⁴, Yeka Aponte⁵

Affiliations

¹ Intramural Research Program, Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse, Baltimore, MD 21224, USA ; Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA ; These authors contributed equally to this work ; Current address: Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD 20892, USA.
² Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA ; These authors contributed equally to this work.
³ Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
⁴ Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA ; [email protected].
⁵ Intramural Research Program, Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse, Baltimore, MD 21224, USA ; Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA ; [email protected].

Abstract

The ability to image neurons anywhere in the mammalian brain is a major goal of optical microscopy. Here we describe a minimally invasive microendoscopy system for studying the morphology and function of neurons at depth. Utilizing a guide cannula with an ultrathin wall, we demonstrated in vivo two-photon fluorescence imaging of deeply buried nuclei such as the striatum (2.5 mm depth), substantia nigra (4.4 mm depth) and lateral hypothalamus (5.0 mm depth) in mouse brain. We reported, for the first time, the observation of neuronal activity with subcellular resolution in the lateral hypothalamus and substantia nigra of head-fixed awake mice.

Keywords: (110.2760) Gradient-index lenses; (170.2150) Endoscopic imaging; (170.2655) Functional monitoring and imaging; (180.0180) Microscopy; (180.2520) Fluorescence microscopy; (180.4315) Nonlinear microscopy.