Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits

Sparta, Dennis R.; Stamatakis, Alice M.; Phillips, Jana L.; Hovelsø, Nanna; Zessen, Ruud van; Stuber, Garret D.

doi:10.1038/nprot.2011.413

Cited by 354 publications

(312 citation statements)

References 22 publications

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“…Single tungsten microelectrodes (1 MΩ and 10-μm tip diameter) were placed in bilateral S1 and V1 approximately between layers IV and V. For VPM, a homemade optrode was used. It consisted of a single tungsten microelectrode (2 MΩ and 10-μm tip diameter) coupled to the fiber using protocols as described previously (77). LFP and MUA recordings were acquired using a 32-channel OpenEphys system with a 30-kHz sampling frequency.…”

Section: Methodsmentioning

confidence: 99%

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

Leong

Chan

Gao

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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One challenge in contemporary neuroscience is to achieve an integrated understanding of the large-scale brain-wide interactions, particularly the spatiotemporal patterns of neural activity that give rise to functions and behavior. At present, little is known about the spatiotemporal properties of long-range neuronal networks. We examined brain-wide neural activity patterns elicited by stimulating ventral posteromedial (VPM) thalamo-cortical excitatory neurons through combined optogenetic stimulation and functional MRI (fMRI). We detected robust optogenetically evoked fMRI activation bilaterally in primary visual, somatosensory, and auditory cortices at low (1 Hz) but not high frequencies (5-40 Hz). Subsequent electrophysiological recordings indicated interactions over long temporal windows across thalamo-cortical, cortico-cortical, and interhemispheric callosal projections at low frequencies. We further observed enhanced visually evoked fMRI activation during and after VPM stimulation in the superior colliculus, indicating that visual processing was subcortically modulated by low-frequency activity originating from VPM. Stimulating posteromedial complex thalamo-cortical excitatory neurons also evoked brain-wide bloodoxygenation-level-dependent activation, although with a distinct spatiotemporal profile. Our results directly demonstrate that lowfrequency activity governs large-scale, brain-wide connectivity and interactions through long-range excitatory projections to coordinate the functional integration of remote brain regions. This low-frequency phenomenon contributes to the neural basis of long-range functional connectivity as measured by resting-state fMRI.fMRI | optogenetic | brain connectivity | low frequency | thalamus T he brain is a highly complex, interconnected structure with parallel and hierarchical networks distributed within and between neural systems (1, 2). This integrative architecture dictates the underlying principles of how brain-wide neural connectivity supports and organizes sensory, behavioral, and cognitive processes (3). Recent advances in structural (2, 4) and functional connectivity (5-12) mapping, as well as neural circuit modulatory tools, such as optogenetics (13, 14), permit detailed, high-resolution neural examinations at unprecedented scales. In particular, functional connectivity mapping using resting-state functional MRI (rsfMRI) produces noninvasive visualization of slow and spontaneous hemodynamic fluctuations in humans (5-9) and animals (10-12). Coherent low-frequency (<1 Hz) fluctuations across functionally coupled, large-scale networks is an intriguing property, although the exact underlying neural bases and functional significance remain unclear. Previous studies integrating large-scale electrical recordings, voltage-sensitive dye (VSD), and Ca 2+ -imaging techniques (15-18) support the hypothesis that slow, oscillating neural activity constrains and elicits these hemodynamic fluctuations. Furthermore, low-frequency activity can temporally synchronize remote brain region...

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Section: Methodsmentioning

confidence: 99%

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

Leong

Chan

Gao

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Optical probes were constructed in which the fiber optic was glued into a stainless steel ferrule assembly with one side extending out of the end of the ferrule implanted into tissue (modified from Sparta et al 2012). The opposing side of the optical probe was polished and connected to a fiber optic leash via a ceramic split sleeve.…”

Section: Optical Stimulation or Inhibitionmentioning

confidence: 99%

Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

et al. 2016

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The basolateral amygdala (BLA) modulates memory consolidation for a variety of types of learning, whereas other brain regions play more selective roles in specific kinds of learning suggesting a role for differential consolidation via distinct BLA pathways. The ventral hippocampus (VH), an efferent target of the BLA, has been suggested to selectively process emotionrelated learning, yet whether the BLA VH pathway modulates memory consolidation, and does so in a learning-specific manner, is unknown. To address this issue, the BLA of male Sprague-Dawley rats was bilaterally transduced to express either ChR2(E123A) or eArchT3.0. Fiber optic probes were implanted in the VH to provide illumination of BLA axons. Rats then underwent a modified contextual fear conditioning task permitting separation of context and footshock learning. On day 1, rats received 3 min of pre-exposure to the apparatus. On day 2, rats were placed into the apparatus, received an immediate footshock, and quickly removed. Retention was tested on day 4. Optical stimulation of the BLA VH pathway following footshock, but not context, training using trains of 40-Hz light pulses enhanced retention. Continuous optical inhibition of this pathway for 15 min starting 25 min after footshock training impaired retention. These findings indicate that BLA VH projections influence the consolidation for footshock, but not context, learning of a modified CFC task and provide direct evidence that BLA projections to other brain regions modulate memory consolidation selectively depending on the kind of learning involved.Learning and memory involves complex interactions among multiple brain regions that play discrete roles in the consolidation of specific kinds of memories. However, work strongly indicates that the basolateral amygdala (BLA) modulates the consolidation of a wide array of memories. It has been hypothesized that the BLA plays this more general role, at least in part, through interactions with distinct regions (McGaugh 2002(McGaugh , 2004McIntyre et al. 2012). BLA connections with forebrain regions such as the hippocampus and striatum that are selectively involved in the consolidation of certain kinds of memories (McDonald 1991;Pitkänen et al. 2000;McGaugh 2002;Malin and McGaugh 2006;Paz et al. 2006;Chavez et al. 2013) suggest that efferent pathways from the BLA may be selectively involved in modulating consolidation for specific kinds of information.Indeed, much evidence suggests that the BLA interacts with the hippocampus during memory consolidation (Packard et al. 1994;Roozendaal et al. 1999;Malin and McGaugh 2006) and that the BLA directly or indirectly influences activity and plasticity in different parts of the hippocampal formation (Ikegaya et al. 1995;Frey et al. 2001;McIntyre et al. 2005;McReynolds et al. 2014;Lovitz and Thompson 2015). These findings suggest pathway mechanisms by which the BLA influences the consolidation of memories regulated by the hippocampal formation. However, the hippocampus comprises different subregions, including dors...

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“…The spinal cord is highly viscoelastic (elastic modulus of 0.5-1 MPa) and experiences up to ~10% of repeated strain during motion [25,26] , presenting a challenge to combined intraspinal neural recording and optical stimulation, since the majority of neural probes and light-delivery devices are comprised of brittle materials [27][28][29] that may cause damage to the neural tissue and fail under repeated deformation [30] . To overcome these limitations, we engineered highly flexible biomimetic all-polymer fiber probes that combine an optical core for optogenetic stimulation and conductive electrodes for simultaneous neural recording.…”

Section: Introductionmentioning

confidence: 99%

Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo

Froriep

Koppes

et al. 2014

Adv Funct Materials

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Restoration of motor and sensory functions in paralyzed patients requires the development of tools for simultaneous recording and stimulation of neural activity in the spinal cord. In addition to its complex neurophysiology, the spinal cord presents technical challenges stemming from its flexible fibrous structure and repeated elastic deformation during normal motion. To address these engineering constraints, we developed highly flexible fiber probes, consisting entirely of polymers, for combined optical stimulation and recording of neural activity. The fabricated fiber probes exhibit low-loss light transmission even under repeated extreme bending deformations.Using our fiber probes, we demonstrate simultaneous recording and optogenetic stimulation of neural activity in the spinal cord of transgenic mice expressing the light sensitive protein channelrhodopsin 2 (ChR2). Furthermore, optical stimulation of the spinal cord with the polymer fiber probes induces on-demand limb movements that correlate with electromyographical (EMG) activity.

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Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits

Cited by 354 publications

References 22 publications

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo

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