High-throughput automated home-cage mesoscopic functional imaging of mouse cortex

Abstract

Mouse head-fixed behaviour coupled with functional imaging has become a powerful technique in rodent systems neuroscience. However, training mice can be time consuming and is potentially stressful for animals. Here we report a fully automated, open source, self-initiated head-fixation system for mesoscopic functional imaging in mice. The system supports five mice at a time and requires minimal investigator intervention. Using genetically encoded calcium indicator transgenic mice, we longitudinally monitor cortical functional connectivity up to 24 h per day in >7,000 self-initiated and unsupervised imaging sessions up to 90 days. The procedure provides robust assessment of functional cortical maps on the basis of both spontaneous activity and brief sensory stimuli such as light flashes. The approach is scalable to a number of remotely controlled cages that can be assessed within the controlled conditions of dedicated animal facilities. We anticipate that home-cage brain imaging will permit flexible and chronic assessment of mesoscale cortical function.

Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal

“…A key advance has been the widespread adoption of head-fixation methods, first developed in the primate neurophysiology community (Wurtz, 1969) and then adapted the use in rodents (Dombeck et a., 2007) (see also Kleinfeld and Griesbeck (2005) and references therein). Both mice (Murphy et al, 2016) and rats (Scott et al, 2013; Scott et al, 2015) can be trained to voluntarily engage in head fixation, indicating that head fixation is not an aversive experience.…”

Long-Term Optical Access to an Estimated One Million Neurons in the Live Mouse Cortex

“…In mice, common methods for repeated imaging across weeks include glass cranial window (Goldey et al, 2014; Holtmaat et al, 2009), thinned skull, (Drew et al, 2010; Silasi et al, 2013; Yang et al, 2010), chemically induced cranial transparency (Silasi et al, 2016), and implanted microendoscope preparations (Barretto et al, 2011; Ziv et al, 2013). These approaches have allowed in vivo imaging studies of sub-cellular morphology (Attardo et al, 2015; Grutzendler et al, 2002; Trachtenberg et al, 2002), ensemble neural Ca 2+ activity (Huber et al, 2012; Peters et al, 2014; Rubin et al, 2015), and aggregate neural activation (Murphy et al, 2016), as well as studies that combined optogenetics and in vivo imaging (Carrillo-Reid et al, 2016; Packer et al, 2015; Rickgauer et al, 2014). …”

Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke

“…The recent paper by Ma et al (Ma et al, 2016b) showed that the hemodynamic contribution is slower than the GCaMP6f signal, with an average temporal delay of 0.86 ± 0.05 s (representing the phase shift between neural activity and total hemoglobin concentration). More recently, by simultaneously recording (wide-field) calcium dynamics and hemodynamics, Wright et al (Wright et al, 2017) showed that sensory evoked responses corresponding to oxygenated and deoxygenated hemoglobin have (i) a very slow onset after stimulus presentation, (ii) delayed peaks and (iii) low peak magnitudes (see also (Murphy et al, 2016)) compared to GCaMP6 fluorescence. These studies suggest that the hemodynamic fluctuations, much slower than calcium-associated neuronal activity, affect the late phase of calcium transients more than the rise.…”