Testing a community proposal for OpenScope

Science
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Title: Investigating the Role of Interneuron Diversity in the Visual Cortex for Object Recognition and Visual Perception using OpenScope

Introduction: The visual cortex plays a crucial role in processing and interpreting visual information. Neuronal diversity, specifically the variety of inhibitory interneurons, is a critical aspect of the functional organization of the visual cortex. Previous research has shown that different interneuron types play unique roles in shaping visual processing, including response selectivity, stimulus integration, and synchronization of network activity. However, the specific contributions of interneuron diversity to visual perception and object recognition remain unclear. The Allen Institute’s OpenScope platform provides an opportunity to investigate this question in a high-throughput and standardized manner.

Objective: The main objective of this proposal is to determine the role of interneuron diversity in the visual cortex for object recognition and visual perception. We aim to uncover how specific interneuron types contribute to the processing of visual stimuli and how their interactions shape the neural representation of objects in the visual cortex.

Methods:

  1. Animal preparation and surgery: We will use transgenic mouse lines expressing Cre recombinase in specific interneuron types (e.g., PV-Cre, SST-Cre, and VIP-Cre mice). These mice will be implanted with multi-electrode arrays in the primary visual cortex (V1) to record neuronal activity.
  2. Visual stimulation: Mice will be subjected to a variety of visual stimuli, including drifting gratings, natural images, and object recognition tasks. We will design custom stimulus sets for each interneuron type, aiming to probe their specific roles in processing visual information.
  3. OpenScope platform: We will utilize the OpenScope platform at the Allen Institute to perform large-scale calcium imaging experiments. The platform will enable simultaneous imaging of hundreds of neurons in the visual cortex, allowing us to examine the interactions between various interneuron types and their contributions to visual perception and object recognition.
  4. Data analysis: We will use advanced data analysis techniques, including dimensionality reduction, spike sorting, and functional connectivity analysis, to identify the specific roles of different interneuron types in processing visual stimuli. In addition, we will apply machine learning approaches to decode object identity and other stimulus features from the population activity of recorded neurons.
  5. Optogenetic perturbations: To further establish causal links between interneuron activity and visual processing, we will perform optogenetic perturbations of specific interneuron types during the presentation of visual stimuli. This will allow us to directly assess the impact of interneuron activity on visual perception and object recognition.

Expected Outcomes:

  1. A comprehensive understanding of the specific roles of different interneuron types in the visual cortex, including their contributions to visual perception and object recognition.
  2. A detailed analysis of the functional interactions between different interneuron types and their impact on visual processing.
  3. Identification of potential therapeutic targets for disorders involving visual processing deficits, such as amblyopia and visual agnosia.

In conclusion, this proposal aims to utilize the OpenScope platform to address an impactful scientific question in the visual cortex. By investigating the role of interneuron diversity in visual perception and object recognition, we hope to advance our understanding of the functional organization of the visual cortex and provide new insights into the neural basis of vision.

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Assuming the goal is to investigate the impact of activating VIP interneurons on the rest of the neuronal network during specific phases of object presentation, we can design several variants of the optogenetic stimulation protocol:

Variant 1: Onset-specific activation

  1. Use a transgenic mouse line expressing Cre recombinase in VIP interneurons (VIP-Cre mice) and inject a Cre-dependent virus carrying the Channelrhodopsin-2 (ChR2) gene into the visual cortex.
  2. Present visual stimuli (e.g., drifting gratings, natural images, or objects) to the mouse.
  3. At the onset of the object presentation, deliver a brief light pulse (e.g., 470 nm, 5-10 ms duration) to activate ChR2-expressing VIP interneurons. Record neuronal activity in the visual cortex using multi-electrode arrays or two-photon calcium imaging.

Variant 2: Sustained activation during object presentation

  1. Follow the same procedure as Variant 1 for animal preparation and visual stimulus presentation.
  2. During the entire duration of the object presentation, deliver continuous or pulsed light stimulation (e.g., 470 nm, 10-20 Hz frequency, 5-10 ms pulse duration) to activate ChR2-expressing VIP interneurons. Record neuronal activity as in Variant 1.

Variant 3: Offset-specific activation

  1. Follow the same procedure as Variant 1 for animal preparation and visual stimulus presentation.
  2. At the offset of the object presentation, deliver a brief light pulse (e.g., 470 nm, 5-10 ms duration) to activate ChR2-expressing VIP interneurons. Record neuronal activity as in Variant 1.

Variant 4: Phase-specific activation during drifting gratings

  1. Follow the same procedure as Variant 1 for animal preparation.
  2. Present drifting gratings as visual stimuli, ensuring the mouse can perceive the full range of grating phases.
  3. During specific grating phases, deliver light stimulation (e.g., 470 nm, 5-10 ms pulse duration) to activate ChR2-expressing VIP interneurons. Record neuronal activity as in Variant 1.

Each of these protocol variants allows for the investigation of how activating VIP interneurons at different times during object presentation impacts the rest of the neuronal network. By comparing the neuronal activity across these variants, researchers can gain insights into the role of VIP interneurons in modulating network activity and visual processing.

Please vote for your preferred variant:

  • Variant 1
  • Variant 2
  • Variant 3
  • Variant 4

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