Research
Dr. David Naylor’s research focuses on disturbances in inhibitory GABAergic and excitatory glutamatergic signaling that occur in disease states such as status epilepticus (SE) and epilepsy. He employs electrophysiological, pharmacological, dynamic imaging, and computational approaches, both in vivo and in vitro, to investigate how alterations in ligand-gated receptors at synaptic and extrasynaptic sites drive pathological circuit behavior. His work involves measuring inhibitory post-synaptic currents (IPSCs), excitatory post-synaptic currents (EPSCs), tonic currents, and evoked and paired-pulse currents under a variety of conditions in both control and diseased brains. These data allow for optimized computational modeling of synaptic, extrasynaptic, and stimulus-evoked multisynaptic responses, creating robust and predictive dynamic representations.
Through dynamic imaging of specific cell populations during epileptogenesis—such as parvalbumin (PV) and somatostatin (SOM) interneuron subsets—Dr. Naylor characterizes how disruptions in cell-to-cell communication contribute to broader circuit dysfunction. His combined experimental and computational strategies examine how disease alters the numbers and subtypes of presynaptic neurons targeting a postsynaptic cell, the contact strength between neuron types, receptor number and distribution, receptor subunit composition and kinetics, and the spatiotemporal dynamics of neurotransmitter presence inside and outside the synaptic cleft. Findings are validated through complementary methods, such as correlating reductions in functional postsynaptic receptors with immunocytochemical evidence of intracellular receptor trafficking.
Dr. Naylor also investigates the effects of drugs and temperature on receptor properties, advancing the development of new tools for therapy screening, simulation, and optimization. His work on temperature dose-response effects—such as the enhancement of GABAergic currents under therapeutic hypothermia—has informed strategies for clinical trial design aimed at maximizing neuroprotection while minimizing harmful seizure activity. These studies have further revealed important mechanistic insights into anesthesia and the exacerbating effects of fever on seizure risk and neurological injury.
Recent projects in Dr. Naylor’s lab examine how stimulation patterns selectively activate interneuron subtypes and GABA-A receptor (GABA-AR) populations. His team has found that high-frequency, high-intensity stimulation is necessary to engage PV interneurons, while SOM interneurons respond to much lower thresholds. Computational modeling of synaptic and extrasynaptic GABA-ARs has shown that at frequencies above 40 Hz, extrasynaptic delta subunit-containing receptors integrate rather than track individual inputs, while synaptic GABA-ARs enter long-lived desensitized states—offering new opportunities for precise tuning of GABAergic circuits.
A central aim of Dr. Naylor’s research is to develop sensitive computational tools capable of extracting core attributes of synaptic and neuronal circuit organization from physiological measurements. By rapidly acquiring micro- and macro-scale physiological data—spanning the functional space of neural networks with high temporal and spatial resolution—his team is building approaches with broad applicability across disease models and strong translational potential for both invasive and non-invasive human neurophysiology.