Circuit Diagrams

Project Summary: Overall Local networks within the spinal cord represent an essential computational layer for the control of limb-driven motor behaviors, integrating descending and sensory inputs to coordinate dexterous motor output. Significant advances have been made in characterizing the developmental programs that specify the core cardinal interneuron types that make up these motor networks. This knowledge has been used to develop a battery of mouse genetic reagents for spinal circuit anatomical and functional dissection.

Project abstract Animals, including humans, interact with their environment via self-generated and continuous actions that enable them to explore and subsequently experience the positive and negative consequences of their actions. As a result of their interactions with the environment, animals alter their future behavior, typically in a manner that maximizes positive and minimizes negative outcomes.

The purpose of this proposal is to disseminate polymer microelectrode arrays and promote their integrated into neuroscience research practice. Such polymer neural interfaces are mechanically compliant to promote stability of the device-tissue interface and versatile in that both surface and penetrating electrode arrays can be produced with the same technology.

Summary Invasive neurostimulation is an established technique in the therapy of movement disorders and epilepsy, and shows promise for amelioration of psychiatric and cognitive disorders. Recently, several implantable neurostimulation hardware platforms have begun to incorporate sensing of cortical and subcortical field potential activity, with the capability for wireless streaming from the internal device to external computers over years.

Project summary Over the past five years, the Allen Institute has built two unique in-house pipelines for in vivo electro- and optical-physiology: together they form the Allen Brain Observatory. We used this observatory to freely and openly share calcium imaging data from ~60,000 cells from 221 running mice viewing standard visual stimuli; in October 2019, we will release Neuropixels electrophysiology recordings from ~100,000 cells from 100 mice under the same conditions, all registered to a common anatomical coordinate system (CCFv3).

The field of neuroscience and the BRAIN Initiative in particular are amassing a wealth of informatics resources for managing, analyzing, and sharing data.

PROJECT SUMMARY Efforts to understand the mechanisms of brain-based disease have been hindered by the limited ability of animal models to reflect the full complexity of human brain and behavior. Brain organoids represent a potential solution, allowing scientists to model human neurodevelopmental and disease processes in-vitro. These multicellular, three-dimensional tissue structures are derived from induced pluripotent stem cells and self-organize to recapitulate aspects of human cortical development.

Project Summary Towards the end of nervous system development, neural circuits are extremely plastic. Small perturbations during this time can cause lifelong circuit and behavioral changes. Not surprisingly, mounting evidence suggests that several neurodevelopmental disorders, including autism spectrum disorder and epilepsy, have origins in defective late neural circuit formation. During this late stage, neural circuits refinement takes place, and components of the mature behavior gradually appear. As this occurs, stimulus-independent bursts of activity sweep through neuronal populations.

PROJECT SUMMARY/ABSTRACT How the brain generates the correct number of neurons and how these neurons determine the size of their arbors to innervate the receptor field is a critical question in neurobiology. The Drosophila visual system is hard wired and iteratively organized into columns, providing an excellent model to answer these questions. Drosophila medulla multicolumnar neurons exhibit 5 to 750 neurons per cell type; each neuron class possesses a distinct morphology and projects its arbors across multiple columns in the optic lobe.

Project Summary There is currently an unmet need for accurate model systems of the human brain to study its cellular and molecular features. The cerebral cortex regulates our cognitive capacity, yet the cellular diversity, circuit formation, and function that establish this potential, largely remains a mystery. The cortex is expanded in humans compared to other species; it contains more cellular diversity and abundance, making model organisms limited for translational studies.