Biology subjects

Davis, G. W.

Publications and source records attributed to Davis, G. W..

5 recordsLinked to original sources

bioRxiv2026

Robust PHP in Adult Hippocampus: Essential Assay Optimizations

Presynaptic homeostatic plasticity (PHP) is a potent form of homeostatic plasticity that has been documented at synapses as diverse as the glutamatergic Drosophila neuromuscular junction (NMJ), cholinergic mammalian NMJ (including human), and glutamatergic synapses in the mammalian brain. Published experimental evidence in favor of PHP in adult hippocampus and cerebellum includes patch-clamp electrophysiology, presynaptic capacitance measurement, calcium imaging, optical reporters of vesicle release and correlated three-dimensional electron microscopy. These studies are grounded in newly optimized experimental protocols that differ substantively from those typically used to study activity-dependent plasticity in neonatal and juvenile slice preparations. Here, we elaborate and extend our assays and methodologies for the study of PHP in the adult mammalian brain. Our assays are designed to optimize synapse, cell and tissue health and minimize the incorporation of unintended adverse experimental conditions that may interfere with the induction and/or expression of PHP. In addition, we provide benchmark criteria for assessment of cell health, necessary for analysis of PHP and, in so doing, advance our understanding of postsynaptic conditions necessary for PHP induction in the adult brain. Our data underscore why PHP may have been previously overlooked, inclusive of a recent manuscript challenging the robust expression of PHP in the mammalian brain (Dou et al., 2026 BioRxiv [preprint]).

neuroscience↗

bioRxiv2025

Assigning Targetable Molecular Pathways to Transdiagnostic Subgroups Across Autism and Related Neurodevelopmental Disorders

The heterogeneity of autism and related neurodevelopmental conditions has impeded accurate prognoses and treatment discovery. Using translational neuroimaging across 135 mouse models (3,515 mice) and two human MRI datasets (n = 1,234 and n = 1,015), we derived participant subgroups from shared neuroanatomical features. These subgroups did not distinguish autism, ADHD, or OCD diagnoses and only modestly differentiated cognitive and behavioural phenotypes. Instead, they mapped onto four molecular pathways: (1) synaptic function; (2) MAPK and Wnt signalling; (3) chromatin modification and cellular stress responses; and (4) broader chromatin, immune, and second-messenger signalling pathways. This framework bridges preclinical models and idiopathic human neurodevelopmental conditions, linking patients to biologically relevant molecular mechanisms.

neuroscience↗

bioRxiv2021

Discoidin domain receptor regulates ensheathment, survival, and caliber of peripheral axons

Invertebrate axons and small caliber axons in mammalian peripheral nerves are unmyelinated but still ensheathed by glia. How this type of ensheathment is controlled and its roles in supporting neuronal function remain unclear. Here we use Drosophila wrapping glia, which ensheathe peripheral axons to study the function and development of non-myelinating ensheathment. We developed a new SplitGal4 intersectional driver to target wrapping glia for genetic ablation and found that loss of wrapping glia severely impaired larval locomotor behavior. We performed an in vivo RNAi screen in Drosophila to identify glial genes required for axon ensheathment during development and identified the conserved receptor tyrosine kinase Discoidin domain receptor (Ddr). In larval peripheral nerves, loss of Ddr resulted in severely reduced ensheathment of axons. We found a strong dominant genetic interaction between Ddr and the fly type XV/XVIII collagen Multiplexin (Mp), suggesting Ddr functions a collagen receptor to drive wrapping of axons during development. Surprisingly, despite severe impairment of ensheathment, the residual wrapping in Ddr mutants was sufficient to support basic circuit function during larval stages. In adult nerves, loss of Ddr from glia decreased long-term survival of sensory neurons and significantly reduced axon caliber in an identifiable neuron without overtly affecting ensheathment. Our data establish a crucial role for non-myelinating glia in peripheral nerve development and function across the lifespan, and identify Ddr as a key regulator of axon-glia interactions during ensheathment and nerve growth.

neuroscience↗

bioRxiv2020

Homeostatic Plasticity Commonly Fails at the Intersection of Autism-Gene Mutations and a Novel Class of Common Phenotypic Modifier

We identify a set of common phenotypic modifiers that interact with five independent autism gene orthologs (RIMS1, CHD8, CHD2, WDFY3, ASH1L) causing a common failure of presynaptic homeostatic plasticity (PHP). Heterozygous null mutations in each autism gene are demonstrated to have normal baseline neurotransmission and PHP. However, we find that PHP is sensitized and rendered prone to failure. A subsequent electrophysiology-based genetic screen identifies the first known heterozygous mutations that commonly genetically interact with multiple ASD gene orthologs, causing PHP to fail. Two phenotypic modifiers identified in the screen, PDPK1 and PPP2R5D, are characterized. Finally, transcriptomic, ultrastructural and electrophysiological analyses define one mechanism by which PHP fails; an unexpected, maladaptive up-regulation of CREG, a conserved, neuronally expressed, stress response gene and a novel repressor of PHP. Thus, we define a novel genetic landscape by which diverse, unrelated autism risk genes may converge to commonly affect the robustness of synaptic transmission.

neuroscience↗

bioRxiv2017

Evolution of mechanisms that control mating in Drosophila males

Genetically wired neural mechanisms inhibit mating between species because even naive animals rarely mate with other species. These mechanisms can evolve through changes in expression or function of key genes in specific sensory pathways or central circuits. Gr32a is a gustatory chemoreceptor that, in D. melanogaster, is essential to inhibit interspecies courtship and sense quinine. Similar to D. melanogaster, D. simulans Gr32a is expressed in foreleg tarsi, sensorimotor appendages that inhibit interspecies courtship in both species, and it is required to sense quinine. Nevertheless, Gr32a is not required to inhibit interspecies mating by D. simulans males. However, and similar to its function in D. melanogaster, Ppk25, a member of the Pickpocket family, promotes conspecific courtship in D. simulans. Taken together, we have identified shared as well as distinct evolutionary solutions to chemosensory processing of tastants as well as cues that inhibit or promote courtship in two closely related Drosophila species.

neuroscience↗