Neuron-Glia Coupling in Neural Circuit Reorganization
Brain research has so far focused on neurons (nerve cells). This is understandable as it is their activity which directly underpins cognition. However, only 30% of the cells that make up the brain are neurons, the remaining 70% are glia.
In the past, glia were viewed as passive support cells for neurons. We now know that glia directly and dynamically interact with neurons in order to regulate the surrounding environment and even neuronal activity itself. There are 3 major sub-types of glia: astrocytes, microglia and oligodendrocytes.
Neurons
Form intricate interconnected circuit networks with each other
Massively parallel neuron-neuron communication (neurotransmission) across the network is underpinned by rapid electrical and chemical signalling and gives rise to cognitive computation
Astrocytes
Traditionally known for facilitating nutritional supply to neurons and maintaining a stable environment through blood-brain barrier formation
Are now known to participate in the regulating both neurotransmission and neuronal circuit organization (formation and elimination of synapses)
Our lab focuses on astrocyte involvement in synapse formation and elimination in the context of treating chronic pain
Microglia
Traditionally known as the sole resident immune cell of the brain
Are now known to participate in regulating neuronal circuit organization under both physiological and pathological conditions
Our lab was one of the first to characterize how microglia directly contact neurons to monitor activity at synapses – this contact can either lead to synapse removal (e.g. in ischaemia) or formation (e.g. in development)
Oligodendrocytes
Traditionally known known for generating the myelin sheath (specialized protein-lipid layer) that surrounds neuronal axons and which is important for regulating nerve conduction velocity (electrical signalling speed)
It is now known that myelin formation is influenced by the level of neuronal activity
Our lab focuses on how changes in myelin formation affect neuronal circuit organization and thus learning and cognition
Research Techniques
Our lab has two major experimental approaches: in vivo mouse brain imaging and electrophysiology. We combine these approaches with behavioural assays with techniques such as molecular biology and immunohistochemistry.
In vivo mouse brain imaging
Whilst we have a number of different imaging capabilities, our mainstay approach is in vivo 2-photon microscopy.
We are able to observe both brain structure and activity using special dyes or proteins that are either stably fluorescent or which fluoresce in response to neuronal activity.
Broadly we have 4 approaches for introducing fluorescent reporters into the mouse brain:
Form intricate interconnected circuit networks with each other
Massively parallel neuron-neuron communication (neurotransmission) across the network is underpinned by rapid electrical and chemical signalling and gives rise to cognitive computation
Intrauterine electroporation of the genetic sequences of fluorescent proteins
Viral (AAV) delivery of the genetic sequences of fluorescent proteins
Once in the brain, fluorescent dyes or proteins are visualized by the delivery of energy via photons in a laser pulse. In 1-photon excitation, a single photon delivers all of the necessary energy to induce fluorescence. In 2-photon excitation, two photons simultaneously deliver all of the necessary energy to induce fluorescence. Thus, 2-photon excitation offers superior signal-noise ratio and depth penetration characteristics as two photon collision events are naturally rare and lower energy (longer wavelength) photons can be used.
Electrophysiology
Whilst we have a number of different electrophysiology capabilities, our mainstay approach is patch clamp electrophysiology.
In patch clamp electrophysiology, we directly measure the changes in membrane potential or “cellular electricity”, which corresponds to intracellular signalling, in a single cell using specialized electrodes. We can then correlate this electrical activity to the actions of specific molecular entities or with subsequent chemical signalling between neurons using pharmacology or molecular biology approaches.
Patch clamp electrophysiology is a powerful tool for probing the mechanistic intricacies of phenomena and rightly deserves its reputation as one of the revolutionary techniques of the 20th century.