Distribution and strength of interlaminar synaptic connectivity in mouse primary visual cortex revealed by two-photon optogenetic stimulation

Hage, Travis A.; Bosma-Moody, Alice; Baker, Christopher A.; Kratz, Megan B.; Campagnola, Luke; Jarsky, Tim; Zeng, Hongkui; Murphy, Gabe J.

doi:10.1101/2019.12.13.876128

Cited by 4 publications

(6 citation statements)

References 86 publications

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“…Here we demonstrated that the Ai203 reporter line can be used to rapidly map synaptic connectivity by recording postsynaptic currents while performing 2p stimulation. Prior 2p mapping experiments used either viral tools that result in opsin expression variability within and across animals, or transgenic lines that do not have soma-targeted expression of opsins (Baker et al, 2016;Hage et al, 2019;Karnani, Jackson, Ayzenshtat, Sichani, et al, 2016;Karnani, Jackson, Ayzenshtat, Tucciarone, et al, 2016;Naka et al, 2019;Packer et al, 2012;Shemesh et al, 2017). The Ai203 reporter line combines the advantages of soma-targeting with the convenience of transgenic expression.…”

Section: Discussionmentioning

confidence: 99%

“…Data are presented as mean ± sem. 2p Synaptic Connectivity Mapping Finally, we tested the use of Ai203 in in vitro synaptic connectivity mapping by using 2p optogenetics to rapidly identify putative monosynaptic connections to a neuron of interest (Baker et al, 2016;Hage et al, 2019;Karnani, Jackson, Ayzenshtat, Sichani, et al, 2016;Karnani, Jackson, Ayzenshtat, Tucciarone, et al, 2016;Naka et al, 2019;Packer et al, 2012;Shemesh et al, 2017). We first measured the effective spatial resolution of photostimulation by recording spiking in an opsin-positive L2/3 pyramidal neuron while stimulating each point in a smaller 3D grid surrounding the cell (Fig.…”

Section: F)mentioning

confidence: 99%

“…Mapping synaptic connectivity is fundamental to obtaining a mechanistic understanding of neural circuits. 2p optogenetic stimulation enables high-throughput stimulation of individual cells to test for monosynaptic connections 14,43,45,[59][60][61][62] . Most prior studies relied on viral expression of the opsin which could lead to biases in the obtain connectivity maps due to incomplete spatial spread of the viral vector or due to direct physiological changes associated with AAV infection 24 .…”

Section: Photostimulation Calcium Imaging and Circuit Mapping In Ai20...mentioning

confidence: 99%

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Ultra-precise all-optical manipulation of neural circuits with multifunctional Cre-dependent transgenic mice

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Sadahiro²,

Hendricks³

et al. 2021

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Causally relating the detailed structure and function of neural circuits to behavior requires the ability to precisely and simultaneously write-in and read-out neural activity. All optical systems that combine two photon (2p) calcium imaging and targeted photostimulation provide such an approach, but require co-expression of an activity indicator, such as GCaMP, and an optogenetic actuator, ideally a potent soma-targeted opsin. In the mammalian brain, such co-expression has so far been achieved by viral transduction, which is invasive and can produce variable, focal, and sometimes toxic overexpression. To overcome this challenge, we developed and validated a Cre-reporter mouse ("Ai203") that conditionally expresses a soma-targeted opsin, ChroME, fused to GCaMP7s. 1p or 2p illumination of expressing neurons in vitro and in vivo produces powerful, precise activation comparable to viral expression of ChroME. The soma-targeted GCaMP7s provides sensitive activity measurements for tracking physiological activity, and the soma-targeted ChroME provides powerful control over neural ensemble activity with holographic optogenetics. We further demonstrate the use of the Ai203 reporter line in 1p optogenetic manipulation of performance on a cortex-dependent visual task and in 2p synaptic connectivity mapping. This new transgenic line could thus greatly facilitate the study of neural circuits by providing a flexible, convenient, and stable tool for all-optical access to large, cell-type specific neural populations throughout the nervous system.

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Section: Discussionmentioning

confidence: 99%

Section: F)mentioning

confidence: 99%

Section: Photostimulation Calcium Imaging and Circuit Mapping In Ai20...mentioning

confidence: 99%

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Ultra-precise all-optical manipulation of neural circuits with multifunctional Cre-dependent transgenic mice

Bounds

Sadahiro²,

Hendricks³

et al. 2021

Preprint

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“…However connections across distant layers are more difficult to interrogate with this method because long axo-dendritic pathways are more likely to be severed (Stepanyants et al, 2009), especially in human cortical tissue that can be several millimeters from pia to white matter. A detailed study of such medium-range connections may require a different methodological approach (Hage et al, 2019).…”

Section: Limitationsmentioning

confidence: 99%

Local Connectivity and Synaptic Dynamics in Mouse and Human Neocortex

Campagnola

Seeman

Chartrand

et al. 2021

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We present a unique, extensive, public synaptic physiology dataset. The dataset contains over 20,000 neuron pairs probed with multipatch using standardized protocols to capture short-term dynamics. Recordings were made in the human temporal cortex and the adult mouse visual cortex. Our main purpose is to offer data and analyses that provide a more complete picture of the cortical microcircuit to the community. We also make several important findings that relate connectivity and synaptic properties to the major cell subclasses and cortical layer via the development of novel analysis methods for quantifying connectivity, synapse properties, and synaptic dynamics. We find that excitatory synaptic dynamics depend strongly on the postsynaptic cell subclass, whereas inhibitory synaptic dynamics depend on the presynaptic cell subclass. Despite these associations, short-term synaptic plasticity is heterogeneous in most subclass to subclass connections. We also find that intralaminar connection probability exhibits a strong layer dependence. In human cortex, we find that excitatory synapses are highly reliable, recover rapidly, and are distinct from mouse excitatory synapses.

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“…Our experiments also revealed strong mutual inhibition among SOM cells, and relatively weak inhibition among PV cells ( Figure 5 ). These results are surprising for two reasons: recent studies on mutual inhibition between interneuron subtypes have shown that SOM cells inhibit most other interneuron subtypes while avoiding inhibiting one another (but see ref 44 ); and PV cells exhibit the opposite connectivity patterns, strongly inhibiting other PV interneurons while making few connections to other genetically distinct interneurons 45 .…”

Section: Discussionmentioning

confidence: 99%

The impact of interneurons on nonlinear synaptic integration in the neocortex

Dorsett

Philpot

Smith

et al. 2020

Preprint

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Excitatory inputs arriving at the dendrites of a neuron can engage active mechanisms that nonlinearly amplify the depolarizing currents. Interneuron-mediated inhibition can modulate this active process, in a subtype-dependent manner. For example, dendrite-targeting inhibition is hypothesized to increase the amplitude of synaptic input required to activate voltage-dependent nonlinear synaptic integration. To examine how inhibition influences active synaptic integration, we optogenetically manipulated the activity of two different subtypes of interneurons: dendrite-targeting somatostatin-expressing (SOM) and perisomatic-targeting parvalbumin-expressing (PV) interneurons. In acute slices of mouse primary visual cortex, electrical stimulation evoked nonlinear synaptic integration that depended on N-methyl-D-aspartate (NMDA) receptors. Optogenetic activation of SOM neurons in conjunction with electrical stimulation resulted in predominantly divisive inhibitory gain control, reducing the magnitude of the nonlinear response without affecting its threshold. PV activation, on the other hand, had a minimal effect on dendritic nonlinearities, resulting in a small subtractive effect. Furthermore, we found that mutual inhibition among SOM interneurons was strong and more prevalent than previously thought, while mutual inhibition among PV interneurons was minimal. These results challenge previous models of inhibitory modulation of active synaptic integration. The major effect of SOM inhibition is not a shift in threshold for activation of nonlinear integration, but rather a decrease the amplitude of the nonlinear response.

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Distribution and strength of interlaminar synaptic connectivity in mouse primary visual cortex revealed by two-photon optogenetic stimulation

Cited by 4 publications

References 86 publications

Ultra-precise all-optical manipulation of neural circuits with multifunctional Cre-dependent transgenic mice

Ultra-precise all-optical manipulation of neural circuits with multifunctional Cre-dependent transgenic mice

Local Connectivity and Synaptic Dynamics in Mouse and Human Neocortex

The impact of interneurons on nonlinear synaptic integration in the neocortex

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