Biology and Neuroscience

Axis 2 of the lab's research, in depth. This page is for the neuroscience or glioscience student who wants to understand how the lab's chronic device and parametric stimulation toolkit functions as an experimental instrument for basic biology questions in adult cortex.

The Device as Instrument

The lab's distinctive scientific position is that chronically implanted devices, paired with parametric perturbation (electrical, ultrasonic, optical, chemogenetic, pharmacological) and longitudinal cellular and electrophysiological readout, constitute an unusually powerful experimental instrument for questions in adult cortical glial and vascular biology that other in vivo preparations cannot address with comparable resolution.

The argument runs as follows. Adult cortical glial and vascular biology has been historically constrained by the absence of good in vivo perturbation tools. Pharmacology lacks cellular and temporal specificity, optogenetics requires viral targeting that itself perturbs the tissue, and acute slice preparations destroy the chronic timescales that matter most for myelin remodeling, mural cell remodeling, and microglial homeostasis. A chronically implanted electrode produces a controlled, quantifiable, longitudinal perturbation of a defined cortical volume, with simultaneous electrophysiological readout, and the perturbation can be parametrically varied (current amplitude, frequency, duration, duty cycle) in ways that pharmacological or optogenetic perturbations cannot match. The device, viewed correctly, is one of the better in vivo tools available for studying activity-dependent and injury-dependent glial and vascular plasticity in adult cortex on biologically relevant timescales.

Open Questions in the Lab

•         Does activity-dependent myelin remodeling occur in adult cortex on behavioral timescales, and what oligodendrocyte and OPC populations contribute?

•         What computational and metabolic roles do mural cells (pericytes, smooth muscle cells) play in chronic neurovascular coupling, and how are these roles altered by perturbation?

•         How do microglia maintain homeostasis under chronic mechanical and electrical input, and what are the temporal dynamics of microglial surveillance during sustained stimulation?

•         How do oligodendrocyte progenitor cells respond to injury and activity in adult cortex, and what fraction of activity-dependent myelin plasticity is OPC-mediated versus mature oligodendrocyte-mediated?

•         What is the metabolic infrastructure (oxygen, glucose, lactate, ATP) that sustains neural firing under chronic stimulation, and how does this infrastructure remodel under perturbation?

•         How do glial computational contributions extend beyond the neuron-centric circuit view, and what new circuit-level phenomena emerge when glia are treated as active computational elements?

Methods and Modalities for Basic Biology Trainees

Trainees on the basic biology track use the lab's full toolkit, with emphasis on the readout side.

•         In vivo two-photon and multiphoton imaging, longitudinal across weeks to months, cell-type-specific labeling through transgenic and viral approaches

•         Conditional and transgenic mouse models, including FusOLcKO (oligodendrocyte-specific cholesterol biosynthesis), oligodendrocyte progenitor cell reporters, microglia-specific conditional manipulations, and mural cell reporters

•         Chronic electrophysiology paired with imaging, for activity-dependent investigation of cellular plasticity

•         Pharmacological intervention for hypothesis testing, with the device serving as the controlled chronic perturbation context

•         Computational modeling and analysis pipelines for cellular dynamics and network-level phenomena