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What are the sources of excitatory or inhibitory cholinergic input to brainstem auditory nuclei?
In the photos on the left, cholinergic axons are filled with a green fluorescent protein. Cholinergic axons with associated boutons can be seen in the ventral nucleus of the lateral lemniscus (VNLL) and the nucleus of the brachium of the inferior colliculus (NBIC), two areas where cholinergic inputs are poorly understood. Arrowheads indicate boutons, which are likely sites of neurotransmitter release. We are currently using viral tract tracing in a newly developed mouse model to determine the sources of this cholinergic input, and we will use electron microscopy to determine whether cholinergic synapses in these and other brainstem nuclei are excitatory or inhibitory.

Do cholinergic cells simultaneously innervate multiple auditory nuclei?
The left panel of the photo on the left shows a neuron that projects simultaneously to the medial geniculate body (MG, yellow), and the cochlear nucleus (CN, green). The right panel shows a neuron that simultaneously projects to the inferior colliculus (IC, magenta) and the cochlear nucleus (green). Both neurons use acetylcholine as a neurotransmitter (cyan). We are currently using fluorescent tract tracing to ask how often cholinergic cells have branching axons to multiple auditory targets, which provides an opportunity for simultaneous release of acetylcholine across auditory nuclei.

What types of cholinergic receptors are associated with ascending or descending auditory circuits?
In the photo on the left, cells in the dorsal part of the inferior colliculus (ICd) have been retrogradely filled via injections into the medial geniculate body (MG, red). These cells also express mRNA for the cholinergic M2 receptor, a type of muscarinic receptor (cyan). We will use a technique called in-situ hybridization to look at the expression of various types of cholinergic receptors within fluorescently-labeled auditory pathways.

Which cholinergic cells are targeted by projections from the auditory cortex, and where do those cholinergic cells project?
In the top photo on the left, a cholinergic cell in the pontomesencephalic tegmentum (PMT) has been trans-synaptically labeled with a green fluorescent protein via a viral injection in the auditory cortex (AC), indicating that this cell receives synaptic input from the auditory cortex. Both dendrites (d) and axons (ax) of the cell are visible, including axons which project to other auditory nuclei. On the bottom, an axon from a similarly-labeled PMT cell that receives auditory cortex input can be seen in the inferior colliculus (IC), indicating release of acetylcholine in the inferior colliculus that may be driven by the auditory cortex. We will use this technique in addition to more traditional tract-tracing techniques to identify nuclei that get cholinergic input from cells targeted by the auditory cortex.