Mesoscale imaging, inactivation, and collaboration in a standardized visual decision-making task

Krasniak, Christopher (April 2022) Mesoscale imaging, inactivation, and collaboration in a standardized visual decision-making task. PhD thesis, Cold Spring Harbor Laboratory.

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Typical neuroscience experiments in the field of decision-making have focused on recording in one or a few brain areas while animals perform a task created by and only used in their own lab with their own custom hardware and software. This makes combining information from these studies to address big questions, such as how information across the whole brain produces a decision, impossible. Big questions such as this are better addressed by collaborations that can enforce standardized methods across their members and can therefore pool their efforts and resources. One such collaboration, the IBL, is focusing on how the mouse brain solves a basic perceptual decision-making task. Towards this goal, in collaboration with the IBL, I have created a standardized visual decision-making task that allows comparison of experiments both between labs and between experimental modalities. I have recorded thousands of neurons across the brain in contribution to a brainwide map of single cell spiking activity during decision-making. These recordings are in contribution to three main scientific goals, a brainwide map of activity related to decision-making, methods for standardized and reproducible electrophysiology recordings, and an electrophysiological atlas of the mouse brain. In my own experiments performed alongside those of the IBL, I used an unbiased inhibition scan across the dorsal cortex to determine the causal cortical areas for performing the IBL task. This revealed that visual cortex inactivation impairs accumulation of contralateral visual information, and secondary motor cortex inactivation biases the starting point of the decision process away from the contralateral side. I additionally performed calcium imaging of the whole mouse dorsal cortex as an independent source of neural recording from the IBL brainwide map. These recordings indicate that task information is broadcast widely across the cortical network, but the strongest information is localized in the expected nodes: initially after stimulus onset in V1, then progressively in M2. These recordings additionally revealed two cortical representations of stimulus or choice expectation: a selective prestimulus suppression, and post stimulus excitation for the expected stimulus-driven areas in V1 and M2, and a potential embodied expectation that is reflected in the paw and torso somatosensory areas. Finally I have shown proof-of-principle experiments that one can simultaneously optogenetically manipulate targeted cortical areas, while monitoring the neural activity across the whole dorsal cortex with widefield calcium imaging. Though this experiment still has a few flaws such as the visual detection of red light, it could lead to many discoveries about the basic function of cortical networks.

Item Type: Thesis (PhD)
Subjects: bioinformatics > computational biology > statistical analysis > bayesian prior
organism description > animal behavior > decision making
Investigative techniques and equipment > lesion
organs, tissues, organelles, cell types and functions > tissues types and functions > motor cortex
neurobiology > neuroscience > neural decoding
organism description > animal behavior > standardization
organs, tissues, organelles, cell types and functions > tissues types and functions > visual cortex
Investigative techniques and equipment > microscopy > wide field calcium imaging
CSHL Authors:
Communities: CSHL labs > Zador lab
School of Biological Sciences > Theses
Depositing User: Sasha Luks-Morgan
Date: 5 April 2022
Date Deposited: 19 May 2022 14:20
Last Modified: 19 May 2022 14:21

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