Precise multimodal optical control of neural ensemble activity

Mardinly, Alan R.; Oldenburg, Ian A.; Pégard, Nicolas C.; Sridharan, Savitha; Lyall, Evan H; Chesnov, Kirill; Brohawn, Stephen G.; Waller, Laura; Adesnik, Hillel

doi:10.1038/s41593-018-0139-8

Cited by 243 publications

(429 citation statements)

References 59 publications

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“…If true, task performance may be recovered if the excitatory effects of noise at trial onset were reduced, and noise-only units were inactivated. Cortical inactivation using methods such as cooling cannot target functionally defined neural populations, and while sophisticated optogenetic techniques exist to do so (Mardinly, Oldenburg et al 2018), such methods are currently limited in clinical applicability for widespread use in humans. We therefore turned to a simpler approach to inactivate neurons, using the acoustic properties of sounds, combined with the adaptive properties of the auditory system (Perez-Gonzalez and Malmierca 2014, Willmore, Cooke et al 2014) to suppress noise-related activity by pre-exposure to noise.…”

Section: What Goes Wrong In Noise?mentioning

confidence: 99%

Signal processing in auditory cortex underlies degraded speech sound discrimination in noise

Town

Wood

Bizley

2019

Preprint

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The ability to recognize sounds in noise is a key part of hearing, and the mechanisms by which the brain identifies sounds in noise are of considerable interest to scientists, clinicians and engineers. Yet we know little about the necessity of regions such as auditory cortex for hearing in noise, or how cortical processing of sounds is adversely affected by noise. Here we used reversible cortical inactivation and extracellular electrophysiology in ferrets performing a vowel discrimination task to identify and understand the causal contribution of auditory cortex to hearing in noise. Cortical inactivation by cooling impaired task performance in noisy but not clean conditions, while responses of auditory cortical neurons were less informative about vowel identity in noise. Simulations mimicking cortical inactivation indicated that effects of inactivation were related to the loss of information about sounds represented across neural populations. The addition of noise to target sounds drove spiking activity in auditory cortex and recruitment of additional neural populations that were linked to degraded behavioral performance. To suppress noise-related activity, we used continuous exposure to background noise to adapt the auditory system and recover behavioral performance in both ferrets and humans. Inactivation by cooling revealed that the benefits of continuous exposure were not cortically dependent. Together our results highlight the importance of auditory cortex in sound discrimination in noise and the underlying mechanisms through which noise-related activity and adaptation shape hearing.

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Section: What Goes Wrong In Noise?mentioning

confidence: 99%

Signal processing in auditory cortex underlies degraded speech sound discrimination in noise

Town

Wood

Bizley

2019

Preprint

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“…However, the temporal fidelity of ChR2mediated optogenetic control of SGN firing seemed limited; auditory brainstem responses broke down even below 100 Hz of stimulation. Higher temporal fidelity of optogenetic SGN stimulation might be achieved when using faster ChRs such as Chronos (Klapoetke et al, 2014), the newly engineered Chronos mutant ChroME (Mardinly et al, 2018), or fast Chrimson mutants (Mager et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos

et al. 2018

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Optogenetic tools, providing non‐invasive control over selected cells, have the potential to revolutionize sensory prostheses for humans. Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. However, most channelrhodopsins do not support the high temporal fidelity pertinent to auditory coding because they require milliseconds to close after light‐off. Here, we biophysically characterized the fast channelrhodopsin Chronos and revealed a deactivation time constant of less than a millisecond at body temperature. In order to enhance neural expression, we improved its trafficking to the plasma membrane (Chronos‐ES/TS). Following efficient transduction of SGNs using early postnatal injection of the adeno‐associated virus AAV‐PHP.B into the mouse cochlea, fiber‐based optical stimulation elicited optical auditory brainstem responses (oABR) with minimal latencies of 1 ms, thresholds of 5 μJ and 100 μs per pulse, and sizable amplitudes even at 1,000 Hz of stimulation. Recordings from single SGNs demonstrated good temporal precision of light‐evoked spiking. In conclusion, efficient virus‐mediated expression of targeting‐optimized Chronos‐ES/TS achieves ultrafast optogenetic control of neurons.

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“…To probe the importance of the identity of individual members in an active population of neurons and their influence on cortical activity and behaviour, we activated specific groups of cells distributed through a volume of visual cortex with two-photon optogenetic stimulation [37][38][39] while performing simultaneous twophoton population calcium imaging of the same volume [40][41][42][43][44][45] . We employed our all-optical approach in mice trained on a visual detection task where task We coexpressed the calcium sensor GCaMP6s [46][47][48] with the excitatory, somatically-restricted opsin C1V1 49,50 in pyramidal cells of L2/3 primary visual cortex (V1) of mice performing a visually guided behaviour.…”

mentioning

confidence: 99%

The influence of visual cortex on perception is modulated by behavioural state

Russell

Yang

Tan

et al. 2019

Preprint

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Correspondence to Michael Häusser: m.hausser@ucl.ac.uk Our understanding of the link between neural activity and perception remains incomplete. Microstimulation and optogenetic experiments have shown that manipulating cortical activity can influence sensory-guided behaviour or elicit artificial percepts. And yet, some perceptual tasks can still be solved when sensory cortex is silenced or removed, suggesting that cortical activity may not always be essential. Reconciling these findings, and providing a quantitative framework linking cortical activity and behaviour, requires knowledge of the identity of the cells being activated during the behaviour, the engagement of the local and downstream networks, and the cortical and behavioural state. Here, we performed two-photon population calcium imaging in L2/3 primary visual cortex (V1) of headfixed mice performing a visual detection task while simultaneously activating specific groups of neurons using targeted two-photon optogenetics during low contrast visual stimulation. Only activation of groups of cells with similar tuning to the relevant visual stimulus led to a measurable bias of detection behaviour. Targeted photostimulation revealed signatures of centre-surround, predominantly inhibitory and like-to-like connectivity motifs in the local network which shaped the visual stimulus representation and partially explained the change in stimulus detectability. Moreover, the behavioural effects depended on overall performance: when the task was challenging for the mouse, V1 activity was more closely linked to performance, and cortical stimulation boosted perception. In contrast, when the task was easy, V1 activity was less informative about performance and cortical stimulation suppressed stimulus detection.Altogether, we find that both the selective routing of information through functionally specific circuits, and the prevailing cortical state, make similarly large contributions to explaining the behavioural response to photostimulation. Our results thus help to reconcile contradictory findings about the involvement of primary sensory cortex in behavioural tasks, suggesting that the influence of cortical activity on behaviour is dynamically reassigned depending on the demands of the task.Understanding the relationship between cortical activity and perception remains one of the most fundamental

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Precise multimodal optical control of neural ensemble activity

Cited by 243 publications

References 59 publications

Signal processing in auditory cortex underlies degraded speech sound discrimination in noise

Signal processing in auditory cortex underlies degraded speech sound discrimination in noise

Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos

The influence of visual cortex on perception is modulated by behavioural state

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