All-optical interrogation of neural circuits in behaving mice

Russell, Lloyd E.; Dalgleish, Henry W P; Nutbrown, Rebecca; Gauld, Oliver M; Herrmann, Dustin; Fişek, Mehmet; Packer, Adam M.; Häusser, Michael

doi:10.1038/s41596-022-00691-w

Cited by 41 publications

(38 citation statements)

References 164 publications

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“…The affine transformation required to map coordinates from SLM space to imaging space was computed through a custom-modified version of open-source software written in MATLAB (github.com/llerussell/Naparm) and calibrated at the start of each experiment by burning arbitrary patterns into a fluorescent plastic slide. Phase masks and galvanometer voltages required to perform photostimulation were generated using NAPARM (50). Voltages were applied to the photostimulation-path galvanometers using PrairieView (Bruker Corporation).…”

Section: Simultaneous Two-photon Optogenetic Stimulation and Calcium ...mentioning

confidence: 99%

All-optical interrogation of excitability during seizure propagation reveals high local inhibition amidst baseline excitability

Shah

Valiante

Packer

2023

Preprint

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Seizures are classically described as an epiphenomenon of hyperexcitability and hypersynchronicity across brain regions. However, this view is insufficient to explain the complex, dynamic evolution of focal-onset seizures in the brain. Recent studies have proposed mechanisms involving an evolution of excitability driven specifically by a spatiotemporally progressing seizure wavefront. These mechanisms attempt to align the abnormal propagation of neural activity with well-known neurobiological parameters, such as excitation-inhibition balance and neuronal connectivity patterns. We describe a direct test of these mechanisms by performing real-time, in vivo investigations of excitability in the acutely epileptic state and during seizure propagation. We used all-optical interrogation to test single-neuronal and local-circuit excitability in the epileptic brain. We demonstrate a surprising paradox during the acutely epileptic state, wherein the brain becomes susceptible to large synchronous inputs, yet single-cell excitability is largely maintained at baseline levels. At a finer scale, excitability of neurons at the single-cell level is related to their distance from the seizure wavefront. Local circuit excitability is increased in the distal penumbra but, crucially, we find inhibition in close proximity to the seizure wavefront. This is in contrast with previously suggested notions of widespread inhibition outside the direct area of action during a focal-onset seizure. These experimental results provide the first direct, in vivo evidence for the precise spatial scale over which single-cell excitability dynamics evolve during seizure propagation, providing support for local inhibitory restraint of seizure propagation.

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Section: Simultaneous Two-photon Optogenetic Stimulation and Calcium ...mentioning

confidence: 99%

All-optical interrogation of excitability during seizure propagation reveals high local inhibition amidst baseline excitability

Shah

Valiante

Packer

2023

Preprint

Self Cite

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“…Simultaneous 2P imaging and 2P optogenetic manipulation of neuronal activity Rickgauer et al, 21 Packer et al, 22 Russell et al, 23 Peterka et al, 24 Nikolenko et al, 25 Papgiakoumou et al, 26 Emiliani et al 27 Chronically implanted prisms Allows imaging at 90 relative to axis of illumination, such as of an entire cortical column en face.…”

Section: Mesoscopic Imagingmentioning

confidence: 99%

Dynamic Fluorescence Imaging in Experimental Epilepsy

Lawlor

Goldberg

2022

Epilepsy Curr

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The ability to develop effective new treatments for epilepsy may depend on improved understanding of seizure pathophysiology, about which many questions remain. Dynamic fluorescence imaging of activity at single-neuron resolution with fluorescent indicators in experimental model systems in vivo has revolutionized basic neuroscience and has the potential to do so for epilepsy research as well. Here, we review salient issues as they pertain to experimental imaging in basic epilepsy research, including commonly used imaging technologies, data processing and analysis, interpretation of results, and selected examples of how imaging-based approaches have revealed new insight into mechanisms of seizures and epilepsy.

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“…Recent advances in multiphoton imaging, opsin development, and targeted photo-stimulation technology has afforded investigators the ability to conduct simultaneous recording and manipulation of neural activity at the single cell level (Adesnik and Abdeladim, 2021; Carrillo-Reid et al, 2017, 2019; Daie et al, 2021; Gill et al, 2020; Jennings et al, 2019; Marshel et al, 2019; Robinson et al, 2020; Russell et al, 2022; Sridharan et al, 2022; Yang et al, 2018). This convergence of technology has led to the ability to directly define causality of discrete neuronal ensembles in mediating a multitude of behaviors (Carrillo-Reid et al, 2019; Daie et al, 2021; Gill et al, 2020; Robinson et al, 2020; Yang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior

Piantadosi

Zhou

Pizzano

et al. 2022

Preprint

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The basolateral amygdala (BLA) is an evolutionarily conserved brain region, well known for valence processing. Despite this central role, the relationship between activity of BLA neuronal ensembles in response to appetitive and aversive stimuli and the subsequent expression of valence-specific behavior has remained elusive. Here we leverage 2-photon calcium imaging combined with single cell holographic photostimulation through an endoscopic lens implanted in the deep brain to demonstrate a direct causal role for discrete ensembles of BLA neurons in the control of oppositely valenced behavior. We report that targeted photostimulation of individual groups of appetitive or aversive BLA neurons shifts behavioral responses toward those behaviors which recruited a specific consumption or avoidance ensemble. Here we identify that neuronal encoding of valence in the BLA is graded and relies on the relative proportion of individual BLA neurons recruited during a stable appetitive or aversive ensemble.

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All-optical interrogation of neural circuits in behaving mice

Cited by 41 publications

References 164 publications

All-optical interrogation of excitability during seizure propagation reveals high local inhibition amidst baseline excitability

All-optical interrogation of excitability during seizure propagation reveals high local inhibition amidst baseline excitability

Dynamic Fluorescence Imaging in Experimental Epilepsy

Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior

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