Acetylcholine is involved in many aspects of auditory function, including plasticity, arousal, and sensory gating. While there have been many studies of acetylcholine in the ear and in the auditory cortex, there is a lack of data on cholinergic innervation of many of the auditory centers that form the ascending auditory pathways. This lack of data has hindered interpretation of physiological studies, especially those in the auditory midbrain. The experiments in this dissertation address questions about cholinergic innervation of the inferior colliculus (IC) and the medial geniculate body (MG), the major auditory centers of the midbrain and thalamus.
We combined immunohistochemistry for choline acetyltransferase (ChAT), a marker of cholinergic cells, with retrograde tracers to address questions about cholinergic circuitry in guinea pigs. We found that the pontomesencephalic tegmentum (PMT) is the source of cholinergic input to the IC. The PMT comprises two cholinergic nuclei: the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus. The PMT is best known as part of the ascending reticular activating system, which affects activation of the cerebral cortex and behavioral arousal via projections to thalamus. We demonstrated that the PMT projections to the MG are similar to PMT projections to other thalamic nuclei, both in the patterns of projections and the involvement of cholinergic and non-cholinergic projecting neurons. In addition, we found that individual PMT cholinergic cells can innervate multiple auditory nuclei, including both ICs, both MGs, or an IC and an MG. Thus, the cholinergic projections are in a position to modulate auditory functions bilaterally and at multiple levels of the auditory system (i.e. auditory midbrain and thalamus).
The results reveal a much broader cholinergic innervation of auditory structures from the PMT than was previously known. This broad innervation is consistent with functions previously associated with the PMT (e.g., modulation of sensory responses during the sleep-wake cycle) as well as other functions only recently related to cholinergic systems, e.g., an essential role in some forms of neuronal plasticity.