Biology subjects

Galanaugh, J.

Publications and source records attributed to Galanaugh, J..

3 recordsLinked to original sources

bioRxiv2025

Indirect pathway neurons in the tail of the striatum regulate inhibitory control over sensory driven behavior

Inhibitory control, or the ability to withhold action in certain situations, is behaviorally essential. Disrupted inhibitory control is linked to various neuropsychiatric symptoms, making it critical to understand the underlying neural basis. We examined how the tail of the striatum (TS), a major basal ganglia sensory hub, regulates actions to sensory stimuli. Mice performed an auditory Go/NoGo task where we recorded cell-specific activity of TS neurons. Both major striatal types were active during target sounds, but non-target sounds preferentially engaged indirect pathway neurons. Temporarily silencing this activity increased errors to non-target stimuli, indicating a role in suppressing inappropriate action. In mice deficient for the synaptic adhesion molecule Neurexin1, a gene linked to autism spectrum disorder and ADHD, TS indirect pathway recruitment was reduced, and these mice demonstrated auditory-specific inhibitory control deficits. Altogether, these findings highlight a subcortical target to potentially improve attentional and behavioral regulation in neurodevelopmental disorders. TeaserPosterior striatal circuits control sensory-guided actions and are disrupted in a rodent model of neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Brain-wide neuronal circuit connectome of human glioblastoma

Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression1-6. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic7-9. The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.

cancer biology↗

bioRxiv2022

The Children's Brain Tumor Network (CBTN) - Accelerating Research in Pediatric Central Nervous System Tumors through Collaboration and Open Science

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Childrens Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTNs 32 member institutions utilize a shared regulatory governance architecture at the Childrens Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4,700 subjects, over 1,500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1,000 tumors and germline material is currently available with data generation for > 5,000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.

cancer biology↗