Organization, plasticity, and regeneration of reticulospinal axons

The National Institute of Neurological Disorders and Stroke, part of the Department of Health and Human Services National Institutes of Health, awarded $580,605 to The Children's Hospital Corporation, doing business as Boston Children's Hospital, on August 7, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853).

The award funds research investigating the organization, plasticity, and regenerative capacity of reticulospinal neurons following spinal cord injury. The project will characterize the functional organization of distinct reticulospinal neuron populations and their roles in controlling spinal functions under intact conditions; assess whether different reticulospinal neuron populations causally contribute to spontaneous functional recovery after incomplete spinal cord injury using advanced technologies; and employ a newly developed method to selectively deliver neurotrophic factors targeting reticulospinal neurons and/or corticospinal neurons to spinal lesions, evaluating their effects on axon regeneration and functional recovery after severe spinal cord injury. Collectively, the research aims to provide insights into the organization, plasticity, and regenerative potential of reticulospinal neurons and to pave the way for novel therapeutic strategies to treat spinal cord injury.

The period of performance runs from August 7, 2026, through May 31, 2031. Work is performed in Boston, Massachusetts.

Abstract

/project summary despite significant progress in axon regeneration research, there are still no effective treatments available for spinal cord injury (SCI) patients. Previous studies have primarily focused on corticospinal neurons (CSNS), which represent only one subset of supraspinal neurons (SPNS). In contrast, other SPNS, in particular reticulospinal neurons (RESNS), have received far less attention. RESNS originate in the brainstem reticular formation, an evolutionarily conserved brain region. Despite their critical role in motor and autonomic functions, the organization and regenerative capacity of RESNS following SCI remain poorly understood. To address this GAP, this study will tackle the following objectives: (1). Functional organization: we will investigate the functional organization of distinct resn populations and their roles in controlling spinal functions under intact conditions. (2). Injury-induced plasticity and spontaneous recovery: using advanced technologies, we will assess whether different resn populations causally contribute to spontaneous functional recovery after incomplete SCI. (3). Therapeutic targeting: we will employ a newly developed method to selectively deliver neurotrophic factors targeting RESNS and/or corticospinal neurons to spinal lesions, evaluating their effects on axon regeneration and functional recovery after severe SCI. Collectively, these studies aim to provide crucial insights into the organization, plasticity, and regenerative potential of RESNS, paving the way for novel and translatable therapeutic strategies to treat SCI.