Design of an implantable artificial dural window for chronic two-photon optical imaging in non-human primates

Trautmann, Eric M.; O’Shea, Daniel J.; Shrestha, Shikhar; Lin, Steven; Ryu, Stephen I.; Shenoy, Krishna V.

doi:10.1109/embc.2015.7320140

Cited by 7 publications

(7 citation statements)

References 12 publications

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“…While there have been prior electrode-based investigations of how movement-related information varies by cell type (Kaufman, Churchland, and Shenoy 2013) or cortical depth (Parikh, Marzullo, and Kipke 2009; Markowitz et al 2011), this approach is limited to either small ensembles of neurons recorded by movable electrodes, or larger but fixed ensembles from higher electrode-count arrays. We’ve recently reported a cortical viewing chamber with a 1 cm diameter usable area (Trautmann et al 2015). With such a chamber, the o-BMI would have access to a relatively large region of motor cortex, from which neurons could be sampled with the much higher density available to optical imaging compared to multielectrode arrays.…”

Section: Insights From Optical Methods For Brain-machine Interface Dementioning

confidence: 99%

“…Some of these challenges are shared with researchers using small animal models, but some arise from the desire to compare optical recordings to the dynamical systems models employed to understand primate neural circuit function. Here we briefly highlight some of these challenges as well as the strategies that we and other groups are pursuing to address them (Trautmann et al 2015; Sadakane et al 2015). …”

Section: Challenges Of Optical Measurement In Nhpsmentioning

confidence: 99%

“…(b) Optical chamber implanted over motor cortex. Adapted from (Trautmann et al, 2015). (c) Viral constructs will be injected into cortex to deliver the calcium reporter gene and other fluorescent markers.…”

Section: Figmentioning

confidence: 99%

“…Existing designs readily permit optical access to cortex for intrinsic optical imaging and optogenetic stimulation (e.g. Grinvald et al 1991; Chen et al 2002; Arieli, Grinvald, and Slovin 2002; Ruiz et al 2013), but changes to the geometry of these chambers ([fig1:chamber]) are likely needed to accommodate the wide objective lenses necessitated by two photon imaging (Trautmann et al 2015). In this imaging chamber, natural dura is replaced by a silicone artificial dura or a glass window, which provides stable, long-term optical access to cortex ([fig1:access]).…”

Section: Introductionmentioning

confidence: 99%

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The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces

O’Shea

Trautmann

Chandrasekaran

et al. 2017

Experimental Neurology

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A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces. Despite these successes, electrophysiology samples sparsely from neural populations and provide little information about the genetic identity and spatial micro-organization of recorded neurons. These limitations have spurred the development of all-optical methods for neural circuit interrogation. Fluorescent calcium signals serve as a reporter of neuronal responses, and when combined with post-mortem optical clearing techniques such as CLARITY, provide dense recordings of neuronal populations, spatially organized and annotated with genetic and anatomical information. Here, we exhort that this methodology, which has been of tremendous utility in smaller animal models, can and should be designed and developed for use with NHPs. We review here several of the key opportunities and challenges for calcium-based optical imaging in NHPs. We focus on motor neuroscience and brain-machine interface design as representative domains of opportunity within the larger field of NHP neuroscience.

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Section: Insights From Optical Methods For Brain-machine Interface Dementioning

confidence: 99%

Section: Challenges Of Optical Measurement In Nhpsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces

O’Shea

Trautmann

Chandrasekaran

et al. 2017

Experimental Neurology

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“…Successful application of calcium imaging in NHPs, however, has been slow to develop for a number of reasons. In particular, difficulties using conventional viruses to express genetically-encoded calcium indicators in the NHP brain (Sadakane et al, 2015a) and imaging artifacts caused by movements of the larger volume NHP brain (Trautmann et al, 2015;Choi et al, 2018) have proven most challenging. Additionally, NHPs have a more mature immune system as compared to rodents that requires sophisticated surgical strategies and neural implant hardware, and limitations exist on the overall number of animals that can be used for trial-and-error technology development (Phillips et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque

Bollimunta

Santacruz

Eaton

et al. 2020

Preprint

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HighlightsFirst demonstration of head-mounted microendoscopic calcium imaging in behaving macaque.Surgical protocols developed for preparing the animal for calcium imaging, including virus injections to express GCaMP and chronic implantation of a GRIN lens to enable optical access to gyral cortex.Proof of concept plug-and-play calcium imaging in behaving macaques with months long stable recording capability allowing populations of individual neurons to be tracked longitudinally.Bilateral calcium imaging from dorsal premotor cortex exhibited dynamics selective to the animal's direction of reach and allowed decoding of the animal's motor behavior Summary A major effort is now underway across the brain sciences to identify, characterize and manipulate mesoscale neural circuits in order to elucidate the mechanisms underlying sensory perception, cognition and behavior. Optical imaging technologies, in conjunction with genetically encoded sensors and actuators, serve as important tools toward these goals, allowing access to large-scale genetically defined neuronal populations. In particular, one-photon miniature microscopes, coupled with genetically encoded calcium indicators and microendoscopic gradient-refractive index (GRIN) lenses, enable unprecedented readout of neural circuit dynamics in cortical and deep subcortical brain regions during active behavior in rodents. This has already led to breakthrough discoveries across a wide array of rodent brain regions and behaviors. However, in order to study the neural circuit mechanisms underlying more complex and clinically relevant human behaviors and cognitive functions, it is crucial to translate this technology to non-human primates. Here, we describe the first successful application of this technology in the rhesus macaque. We identified a viral strategy for robust expression of GCaMP, optimized a surgical protocol for microendoscope GRIN lens insertion, and created a chronic cranial chamber and lens mounting system for imaging in gyral cortex. Using these methods, we demonstrate the ability to perform plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from over 100 genetically-targeted neurons simultaneously in dorsal premotor cortex while the macaque performs a naturalistic motor reach task with the head unrestrained and freely moving. The recorded population of neurons exhibited calcium dynamics selective to the direction of reach, which we show can be used to decode the animal's trial-by-trial motor behavior. Recordings were stable over several months, allowing us to longitudinally track large populations of individual neurons and monitor their relationship to motor behavior over time. Finally, we demonstrate the ability to conduct simultaneous, multi-site imaging in bilateral dorsal premotor cortices, offering an opportunity to study distributed networks underlying complex behavior and cognition. Together, this work establishes headmounted microendoscopic calcium imaging in macaque as a powerful new approach for studying the neural ci...

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The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo

Yu,

Adsit

et al. 2023

Nat Methods

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Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a more than 4 mm2 field of view with submicrometer lateral resolution and is compatible with commonly used multiphoton imaging systems. A novel mechanical design, wider than typical microscope objectives, enabled this combination of specifications. We share the full optical prescription, and report performance including in vivo two-photon and three-photon imaging in an array of species and preparations, including nonhuman primates. The Cousa objective can enable a range of experiments in neuroscience and beyond.

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Design of an implantable artificial dural window for chronic two-photon optical imaging in non-human primates

Cited by 7 publications

References 12 publications

The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces

The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces

Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque

The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo

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