Experimental Approaches

Acute brain slice electrophysiology

We make whole-cell patch-clamp recordings from living neurons in slices of living brain tissue. This approach is the best way to investigate the electrical properties of neurons and their synaptic connections. Using pharmacological agents we investigate how neurotransmitters and their receptors transform neural signals.

Two neurons recorded at the same time. In the upper trace, the presynaptic neuron fires action potentials. The lower trace shows the resulting excitatory synaptic response of the postsynaptic neuron as its receptors bind to the neurotransmitter released by each presynaptic action potential.

The green neurons were labeled by an AAV injected into a distant part of the brain that infected their axons and caused the entire cell to light up. The red neurons were labeled not by a viurs, but instead by this transgenic mouse's genomic DNA.

Viral tracing

Adenoassociated viruses (AAVs) can be used to make specific neurons express a variety of proteins throughout their length, from dendrite tip to axon tip. This approach allows us to address where neurons send their fibers and thus, their electrical signals. Our lab pushes the boundaries of how viruses can be used as tools to trace neural circuits, experimenting with viruses that can jump to presynaptic and postsynaptic neurons.

Optogenetics

Expressing the light-gated ion channel channelrhodopsin in neurons allows us to control their activity with light. We use this approach to identify the connectivity and synaptic function of specific populations of neurons.

The green axon expresses channelrhodopsin, so that light flashes cause transmitter release onto the magenta cell's dendrite. The magenta cell is a unipolar brush cell.

In the recorded cell shown to the left, light flashes caused excitatory synaptic currents (top) and a burst of action potentials (bottom).

This neuron in the dorsal cochlear nucleus responds to sound with an increase in action potential firing.Credit: Jeffrey Tang

In vivo electrophysiology

We can record the activity of neurons in the intact brain to explore how they respond to real-world stimuli, such as sounds. By combining this approach with optogenetics we can control the activity of populations of neurons and address their function in hearing and balance.

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