Research
Plasticity (Hebbian plasticity), can be a double-edged sword. It allows the neural circuit to incorporate new information and adapt to a new environment. It can also make the neural circuit susceptible to perturbations and brings instability into the system. Other forms of plasticity (under the general name homeostatic plasticity) may work as counteracting mechanisms to keep Hebbian plasticity in check. What mechanisms underlie homeostatic plasticity and how these different forms of plasticity coordinate and reconcile with each other at different temporal and spatial scales remains largely unknown.
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Movie courtesy of Dr. Masateru Hiramoto
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The brain structure we focus on is called the optic tectum, which is the equivalent of the superior colliculus in the mammalian brain. As the superior colliculus, the optic tectum receives direct inputs from multiple sensory modalities, and is in charge of coordination of sensory-motor integration. Retinal ganglion cell axons start innervating optic tectum after stage 39, the same time when tadpoles start free swimming. This means that the nascent visual circuit needs to be fully functional while at the same time still being actively refined and tuned by visual experience, as all developing sensory circuits are. By manipulating the visual experience the animal receives, or interfering with molecular genetic manipulations, we can facilitate or stall the maturation of the visual circuit, and interrogate how plasticity and stability (of the circuit) interact from molecular to cellular to circuit level.
GABAergic inhibitory neurons comprise about 30% of tectal neuronal population, as shown here by GABA immunostaining in serial vibratome sections of optic tectum (Green: GABA; Blue: Dapi; stage 47). At this developmental stage, tectal inhibitory neurons appear to be rather homogeneous in terms of their dendritic morphology and electrophysiological properties. However, in response to different visual experience, the inhibitory neuronal population displays distinct functional heterogeneity: two subgroups of inhibitory neurons with exact opposite plasticity profiles can be revealed by both structural plasticity of the dendritic arbors and functional plasticity of visually-evoked Ca responses, as measured by in vivo time-lapse imaging of individual neurons.
What are these inhibitory neuronal subtypes? Are they intrinsically defined? Will their plasticity profile be affected by prior experience? What is the advantage or functional relevance of having two antagonizing inhibitory neuronal populations in the circuit? So begins our quest ...
In our lab, we use multidisciplinary tools, ranging from molecular genetics and biochemistry, to time-lapse structural and functional in vivo imaging, as well as behavioral test in live animals, to ask our questions. Click on the above pictures to learn more about each technique.
