Sources of cholinergic input to the inferior colliculus

Abstract

We combined retrograde tracing with immunohistochemistry for choline acetyltransferase to identify the source of cholinergic input to the inferior colliculus (IC). Injection of a retrograde tracer into one IC labeled cells in many brainstem nuclei. Retrogradely-labeled cells that were also immunoreactive for choline acetyltransferase were identified in two nuclei in the midbrain tegmentum: the pedunculopontine tegmental nucleus (PPT) and the laterodorsal tegmental nucleus (LDT). More PPT and LDT cells project ipsilaterally than contralaterally to the IC and, on both sides, there are more projecting cells in the PPT than in the LDT. Double-labeled cells were not found in any other brainstem nucleus. A common feature of cholinergic cells in PPT and LDT is collateral projections to multiple targets. We placed different retrograde tracers into each IC to identify cells in PPT and LDT that project to both ICs. In both PPT and LDT, a substantial proportion (up to 57%) of the immunoreactive cells that contained tracer from the contralateral IC also contained tracer from the ipsilateral IC. We conclude that acetylcholine in the IC originates from the midbrain tegmental cholinergic nuclei: PPT and LDT. These nuclei are known to participate in arousal, the sleep/wake cycle and prepulse inhibition of acoustic startle. It is likely that the cholinergic input to the IC is directly associated with these functions.

Connectional Modularity of Top-Down and Bottom-Up Multimodal Inputs to the Lateral Cortex of the Mouse Inferior Colliculus

“…BDA was chosen as it has proven to be a superior anterograde tracer in our hands and others (Ling et al, 2012). For subcortical injections, BDA was injected iontophoretically using 5 A positive current pulses (50% duty cycle) for 10 -20 min.…”

“…Previous studies that have plotted the terminals in the LC arising from the spinal trigeminal nucleus have shown that they terminate in distinctive clusters that resemble the input patterns from the dorsal column nuclei and somatosensory cortex (Wise and Jones, 1977;Wiberg and Blomqvist, 1984;Wiberg et al, 1987). Input to the LC from auditory brainstem structures, such as the cochlear nucleus and the lateral lemniscus, is largely restricted to layer 3, suggesting that this input is extramodular (Coleman and Clerici, 1987;González-Hernández et al, 1996;Gabriele et al, 2000;Malmierca et al, 2005;Loftus et al, 2008). In a dual anterograde tract-tracing study, Zhou and Shore (2006) labeled afferents to the LC from the cochlear nucleus and spinal trigeminal nucleus in the guinea pig.…”

“…Other brain regions have also been revealed to have neurochemical and connectional modularity that ultimately proved important in understanding their function. Within the auditory system, the ventral nucleus of the lateral lemniscus contains discontinuous patches of labeled afferents and efferents that are thought to represent interdigitating frequencyband components (Malmierca et al, 1998). The striatum is organized into compartments, striosomes and matrix, which, similar to the LC, have neurochemical and connectional segregation, and also play distinct roles in motor physiology (Graybiel and Ragsdale, 1978;Kincaid and Wilson, 1996;Fujiyama et al, 2015).…”

“…While this role may be accurately ascribed to the central nucleus of the IC (CNIC), the lateral cortex (LC) likely performs a distinct function, as evidenced by its multimodal connectivity (Tokunaga et al, 1983;Coleman and Clerici, 1987). The major ascending inputs to the LC arise from somatosensory brainstem nuclei, including the dorsal column nuclei and spinal trigeminal nucleus, and from other subdivisions within the IC (Jane and Schroeder, 1971;Schroeder andJane, 1971, 1976;RoBards et al, 1976;Hand and Van Winkle, 1977;Willard and Martin, 1983;Björkeland and Boivie, 1984;Paloff and Usunoff, 1991;Li and Mizuno, 1997). The LC also receives top-down information from the superior colliculus (SC) and the somatosensory, auditory, and visual cortices (Cooper and Young, 1976;Robards, 1979;Adams, 1980;Faye-Lund, 1985;Winer et al, 1998).…”

“…In the rat, the LC contains an additional level of compartmental organization that distinguishes it from the CNIC: layer 2 of the LC contains a network of modules that stain positively for a number of neurochemical and metabolic markers, including glutamic acid decarboxylase-67 (GAD-67), acetylcholinesterase (AChE), parvalbumin (PV), nicotinamide adenine dinucleotide phosphatediaphorase (NADPH-d), and cytochrome oxidase (CO) (Mugnaini and Oertel, 1985;Chernock et al, 2004;Ito et al, 2009;Choy Buentello et al, 2015). Though the functional significance of these modules remains unknown, their spatial distribution bears striking resemblance to the clusters of terminals formed by sensory inputs to the LC (Huffman and Henson, 1990;Cramer and Gabriele, 2014).…”