Optogenetics reveals paradoxical network stabilizations in hippocampal CA1 and CA3

Jong, Laurel Watkins de; Nejad, Mohammadreza Mohagheghi; Yoon, Euisik; Cheng, Sen; Diba, Kamran

doi:10.1016/j.cub.2023.03.032

Cited by 4 publications

(6 citation statements)

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“…5(c). The landmark LFPs from both hippocampi were also simultaneously monitored as shown in It is noteworthy that these responses from the adjacent shanks were caused by the downstream and/or upstream activation of the hippocampal circuitry, as previously reported in [17,18]. Fig.…”

Section: In Vivo Experimentsmentioning

confidence: 78%

“…Advances in microfabrication technologies led to invention of high-density micro-LED (µLED) optoelectrodes, expanding the application of the optogenetics to extensive investigation of the brain circuits with a single-cell resolution. For instance, various neuronal circuit dynamics in hippocampus, such as excitatory/inhibitory networks, paradoxical short-and long-range interactions, and functional connections among three different types of neurons, were observed through optical perturbations using the high-density µLED optoelectrodes [13][14][15][16][17][18]. Furthermore, the µLED optoelctrodes may also enable studying striatum, amygdala, and other architecturally complex regions in deep-brain where large-scale high-density illumination is necessary to untangle microcircuits and their behavioral outcomes [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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A compact, ultrahigh-density headstage with high-fidelity hybrid integration for large-scale deep-brain opto-electrophysiology

Oh,

Kim,

Lopez Ruiz

et al. 2023

Preprint

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Recent neuroscientific research seeks to comprehend the sophisticated deep-brain networks of neural circuits consisting of large scale neuronal ensembles across multiple brain regions. An ideal way to unveil the complex connectome might be stimulating individual neurons with high spatial resolution in a broad range of brain, while seamlessly monitoring the correspondent neuronal activities. Optogenetics is known as a key technology to enable such a goal thanks to its high spatial and temporal selectivity in neuromodulation. Existing silicon probe technologies have been able to partially achieve such a goal by recording broad region of brain activities through multiple electrodes per shank, but those cannot complete perfect coverage due to the limited channel counts for the optogenetic stimulation. Here, we present an high-channel-count optogenetic system with simultaneous 256 recoding and 128 optogenetic stimulation sites, exhibiting the highest channel density ever reported, enabled by a flexible polyimide cable-based hybrid-integration of a low-stimulation-artifact micro-LED (µLED) opto-electrode with a low-power and -noise, area-efficient CMOS interfacing integrated-circuit (IC). The presented optogenetic system provides 256-neuron-size electrodes (11 × 15 µm2) with a 40 µm inter-electrode pitch for high spatial oversampling in recording and 128-soma-size µLEDs (8 × 11 µm2) with a 20 µm inter-LED pitch for single-cell resolution in stimulation, resulting in a vertical span of 640 µm and a horizontal span of 2,100 µm with a total 8 shanks. For versatility in optogenetics-based experiments from small rodents to primates with user-preferable settings, the system base that provides programmability of recording and stimulation parameters and rest of signal processing, such as filtering, digitization, and data transmission including serial peripheral interface (SPI) has also been designed within small area of 23.8 × 28.8 mm2with only 3.5-gram weight, resulting in the highest channel density both in size (0.56 channels/mm2) and weight (109.71 channels/gram) among the state-of-the-art optogenetics-based neuromodulation systems. To verify the system operationin vivo, a compact optogenetics headstage has been also fabricated. Using the prepared optogenetic headstage, 169 isolated neurons have been observed with various stimulation intensities. The results offered in this article indicate that the presented hybrid integrated ultrahigh-density, high-channel-count headstage can be used to realize the massive-scale in-depth brain studies with optogenetics.

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Section: In Vivo Experimentsmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

A compact, ultrahigh-density headstage with high-fidelity hybrid integration for large-scale deep-brain opto-electrophysiology

Oh,

Kim,

Lopez Ruiz

et al. 2023

Preprint

Self Cite

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show abstract

“…Representative results from successful, focal stimulation of neural activity in the rat hippocampus in vivo are shown in Methods video S9 , Figure 11 and in published studies. 1 , 12 , 13 , 14 , 15 , 16 , 17 An example of successful neural suppression is shown in Figure 12 for the rat hippocampus. Following the above protocol will ensure a high probability of successful neural perturbation with μLED probes.…”

Section: Expected Outcomesmentioning

confidence: 99%

“…These factors can result in excitation or suppression that spreads more strongly to neighboring shanks than shown in Figures 11 and 12 , or even in paradoxical increases/decreases in firing which may indicate inhibitory stabilization. 1 See also Methods video S9 for an example of successful, focal stimulation of neural activity on individual shanks in region CA1 of the rat hippocampus in vivo.…”

Section: Expected Outcomesmentioning

confidence: 99%

“…As such, μLED probes are not designed for large scale stimulation or silencing of entire brain regions and are currently only compatible with blue-light sensitive opsins. Custom-build optrodes with light delivery via large diameter optical fibers 1 , 18 , 19 may be better suited for such large scale stimulation/silencing, such as to test the role of a specific group of neurons in a given task (though even small numbers of neurons may prove sufficiency/necessity 20 ).…”

Section: Limitationsmentioning

confidence: 99%

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