RESEARCH

Overview

We are investigating the influence of neural activity and early experience on the development and refinement of brain circuits at the systems, cellular, and molecular levels using mouse, Xenopus tadpole and zebrafish models.

Research TOPICS

Circuit refinement

The brain is constantly remodeling throughout development. We observe how different components of the circuit change morphologically and functionally in response to genetic, pharmacological, and visual experience manipulations. We have provided some of the first in vivo evidence for Hebbian (coactivity-induced) and Stentian (asynchrony-induced) structural plasticity.

Neuron-glia interactions

We examine the roles of various glia – radial astrocytes, microglia, and oligodendrocytes – in the refinement and function of the developing retinotectal system. We also ask how these intercellular interactions may be altered under disease conditions.

Live imaging methods

As one of the first in vivo microscopy labs in Canada, we have developed a wide range of tools for the labeling, imaging and quantification of morphometric data from brain cells. We also collaborate with other researchers at McGill University and the Canadian Neurophotonics Platform on various tool development projects, including in vivo optimisation of fluorescent sensors for two-photon imaging and of enzymatic biosensor electrodes for electrophysiology.

Our Tools

Xen & zebrafish visual system

The fish and frog retinotectal systems are well suited for the study of circuit development and function, particularly in response to changes in activity. Xenopus laevis and Danio rerio embryos develop externally, allowing for embryonic, sensory, and pharmacological manipulations early in development. We exploit the power of zebrafish genetics and the ease of in vivo electrophysiology in tadpoles to mechanistically dissect the development visual circuits.

In vivo multiphoton microscopy

We use multiphoton laser scanning microscopy for three-dimensional imaging of fluorescently labeled cells in the intact animal. This technique permits us to follow morphological changes of brain cells over minutes to days while manipulating gene expression and neural activity to determine the rules and mechanisms of activity-dependent circuit refinement. We also use this method to perform high speed 4D calcium imaging to extract functional data, including topographic maps and neuron-glia communication.

Whole-cell electrophysiology

Whole-cell patch clamp recordings from cells in the optic tectum of Xenopus tadpoles or (in collaboration with the lab of Tim Kennedy) mouse hippocampal slices allows us to study synaptic properties in developing and mature circuits. We can also record in the intact tadpole brain while presenting visual stimuli to the contralateral eye through a multi-fibre optical array to extract subthreshold receptive field properties. With the Mauzeroll Lab we have also developed amperometric probes for the detection of D-serine release in vivo.

Additional TOPICS

Ongoing lab interests and techniques include:

amperometric probes for D-serine detection
topographic map extraction from sensory-evoked calcium signal
RNAseq analysis of plasticity-associated genes
half-tadpole morpholino oligonucleotide gene knockdown
microglial trogocytosis of synapses
embryonic immune activation model of neurodevelopmental disorders
CRISPR transgenesis and knock-in techniques in fish and frogs
state-dependent plasticity (modulation by sleep and alert states)
computational visual scene reconstruction from neuronal activity patterns