CircuitATLAS: Agentic reasoning over a systems neuroscience knowledge graph for target discovery in circuitopathies

Key points

• Drug discovery for neurological disease has traditionally centered on the molecules altered by disease.1
• Here, we ask which otherwise unaltered molecular control points can be engaged to restore pathological neural circuits toward functional states.1
• Finally, we introduce a human-governed in vivo lab-in-the-loop linking hypothesis generation to experimental iteration.1
• Within this framework an agent nominated ATP1A3, the neuronal alpha3 Na+/K+-ATPase, as a control point on cortical excitability; interneuron-restricted expression of ATP1A3 abolished the beta- and gamma-band response to a focal 4-aminopyridine challenge in vivo, and the validated target was then carried into a structure-guided small-molecule campaign terminating in a defined assay to resolve the direction of modulation.1

Sources (1)

• [1]CircuitATLAS: Agentic reasoning over a systems neuroscience knowledge graph for target discovery in circuitopathies
  arXiv (AI, ML, NLP, CV, robotics, multi-agent) · Oct 7, 08:19 AM

  We present CircuitATLAS, a provenance-grounded systems-neuroscience knowledge graph and agentic framework for target discovery in circuitopathies.

  Drug discovery for neurological disease has traditionally centered on the molecules altered by disease.

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