Professor Josh Huang’s team has provided the neuroscience community with a set of powerful new tools that exploit the exquisite specificity of genetics to see and manipulate particular neuronal subtypes in the brains of living, behaving mice.
They have engineered 20 different mouse lines, each containing a genetic “handle” that provides access to a specific cell type. Their quarry: neurons that release the neurotransmitter GABA. Comparatively scarce and poorly understood, GABA neurons play the indispensable role of inhibiting signals sent by much more numerous excitatory neurons. When inhibition malfunctions, a fine balance is upset which may contribute to a range of illnesses such as epilepsy, autism and schizophrenia.
In one experiment, postdoc Hiroki Taniguchi imaged the entire mouse brain, in lengthwise cross-section. The elongated wedge-shaped section at the top is the cortex, with the “S”-shaped hippocampus tucked beneath it. The cauliflower-like cerebellum is at the rear (r) and the knob-like olfactory bulb at the front (l). Each green dot indicates a single GABA cell of a particular type: all in this image contain the neuropeptide somatostatin, labeled to express a green fluorescent reporter molecule. Other GABA subtypes uniquely express other proteins, which make them similarly visible, brain-wide, in other mouse lines. The technology can also be used to make particular GABA cells responsive to beams of colored laser light (optogenetics) or to incorporate deactivated viruses, which enable researchers to observe GABA cells in action in the young brain, forging connections with excitatory neurons. We can expect many discoveries in the period ahead.
Z. Josh Huang
Charles Robertson Professor of Neuroscience
Ph.D., Brandeis University, 1994