Descending projections from the inferior colliculus to the dorsal cochlear nucleus are excitatory

Abstract

Ascending projections of the dorsal cochlear nucleus (DCN) target primarily the contralateral inferior colliculus (IC). In turn, the IC sends bilateral descending projections back to the DCN. We sought to determine the nature of these descending axons in order to infer circuit mechanisms of signal processing at one of the earliest stages of the central auditory pathway. An anterograde tracer was injected in the IC of CBA/Ca mice to reveal terminal characteristics of the descending axons. Retrograde tracer deposits were made in the DCN of CBA/Ca and transgenic GAD67-EGFP mice to investigate the cells giving rise to these projections. A multiunit best frequency was determined for each injection site. Brains were processed by using standard histologic methods for visualization and examined by fluorescent, brightfield, and electron microscopy. Descending projections from the IC were inferred to be excitatory because the cell bodies of retrogradely labeled neurons did not colabel with EGFP expression in neurons of GAD67-EGFP mice. Furthermore, additional experiments yielded no glycinergic or cholinergic positive cells in the IC, and descending projections to the DCN were colabeled with antibodies against VGluT2, a glutamate transporter. Anterogradely labeled endings in the DCN formed asymmetric postsynaptic densities, a feature of excitatory neurotransmission. These descending projections to the DCN from the IC were topographic and suggest a feedback pathway that could underlie a frequency-specific enhancement of some acoustic signals and suppression of others. The involvement of this IC-DCN circuit is especially noteworthy when considering the gating of ascending signal streams for auditory processing. J. Comp. Neurol. 525:773-793, 2017. © 2016 Wiley Periodicals, Inc.

Using Cortical Neuron Markers to Target Cells in the Dorsal Cochlear Nucleus

“…Aberrant activity in any cochlear nucleus subregions can trigger upstream changes as cochlear nucleus neurons relay auditory signals to higher areas of the auditory pathway (Kraus et al, 2011;Coomber et al, 2015). Abnormal activity from auditory cortex and inferior colliculus can also produce downstream alterations in the DCN as its cells receive feedback through descending auditory fibers (Winer and Prieto, 2001;Milinkeviciute et al, 2016).…”

Descending Axonal Projections from the Inferior Colliculus Target Nearly All Excitatory and Inhibitory Cell Types of the Dorsal Cochlear Nucleus

“…Anterograde trans-synaptic labeling of DCN neurons that receive input from IC To test the hypothesis that fibers from IC drive cells in the granule cell domain, the identity of those cells must be determined. We focused on the ipsilateral IC-DCN projection because it is much larger than the contralateral projection (Milinkeviciute et al, 2017). We injected a Cre-recombinase (Cre) expressing adeno-associated virus (AAV1-Syn-Cre) into the right IC of Ai9 reporter mice that express the red fluorescent protein tdTomato in cells that contain Cre (Fig.…”

“…AAV1-Chronos-GFP (1.4e13 GC/ml, Addgene) was used instead of the ChR2-Venus virus in a single experiment that yielded ChR2evoked EPSCs in one granule cell and one Golgi cell. We did not differentiate whether the injection site included the central nucleus or the lateral/external cortex of the IC, because previous work in the mouse showed that all major subdivision of the IC project to DCN (Milinkeviciute et al, 2017).…”

“…The cell types in the granule cell region that surrounds DCN include granule cells, Golgi cells, and unipolar brush cells (UBCs) and presumably these integrate extrinsic multisensory (nonauditory) signals. While it might be expected that this region conveys all nonauditory nerve input to DCN principal cells, anatomical data shows that the descending IC projection terminates across the deep layers of the DCN (Milinkeviciute et al, 2017), which contains numerous UBCs, but also a number of other cell types that receive direct input from the auditory nerve and are not thought to receive descending sensory input. Our goal was to identify which cell types across the entire DCN receive descending input from IC and test their postsynaptic responses to address whether they are indeed glutamatergic and whether they are capable of driving action potential firing.…”

“…The IC, which is the primary target of the projections from DCN, sends signals back to DCN that have been inferred to be glutamatergic based on anatomical data (Milinkeviciute et al, 2017). The cell types in the granule cell region that surrounds DCN include granule cells, Golgi cells, and unipolar brush cells (UBCs) and presumably these integrate extrinsic multisensory (nonauditory) signals.…”