Elsevier

Hearing Research

Volume 306, December 2013, Pages 131-144
Hearing Research

Research paper
Auditory cortical axons contact commissural cells throughout the guinea pig inferior colliculus

https://doi.org/10.1016/j.heares.2013.10.003Get rights and content

Highlights

  • A minority of commissural cells in the inferior colliculus (IC) are GABAergic.

  • Auditory cortical (AC) axons contact many commissural cells in the ipsilateral IC.

  • AC axons contact GABAergic and non-GABAergic commissural cells.

  • The IC commissure provides a major route for AC effects on the contralateral IC.

Abstract

Projections from auditory cortex (AC) affect how cells in both inferior colliculi (IC) respond to acoustic stimuli. The large projection from the AC to the ipsilateral IC is usually credited with the effects in the ipsilateral IC. The circuitry underlying effects in the contralateral IC is less clear. The direct projection from the AC to the contralateral IC is relatively small. An unexplored possibility is that the large ipsilateral cortical projection contacts the substantial number of cells in the ipsilateral IC that project through the commissure to the contralateral IC.

Apparent contacts between cortical boutons and commissural cells were identified in the left IC after injection of different fluorescent tracers into the left AC and the right IC. Commissural cells were labeled throughout the left IC, and many (23–34%) appeared to be contacted by cortical axons. In the central nucleus, both disc-shaped and stellate cells were contacted. Antibodies to glutamic acid decarboxylase (GAD) were used to identify GABAergic commissural cells. The majority (>86%) of labeled commissural cells were GAD-immunonegative. Despite low numbers of GAD-immunopositive commissural cells, some of these cells were contacted by cortical boutons. Nonetheless, most cortically contacted commissural cells were GAD-immunonegative (i.e., presumably glutamatergic).

We conclude that auditory cortical axons contact primarily excitatory commissural cells in the ipsilateral IC that project to the contralateral IC. These corticocollicular contacts occur in each subdivision of the ipsilateral IC, suggesting involvement of commissural cells throughout the IC. This pathway – from AC to commissural cells in the ipsilateral IC - is a prime candidate for the excitatory effects of activation of the auditory cortex on responses in the contralateral IC. Overall this suggests that the auditory corticofugal pathway is integrated with midbrain commissural connections.

Introduction

The auditory cortex (AC) is the source of a large projection to the inferior colliculus (IC), a major midbrain center of auditory integration. Stimulation or inactivation of this corticocollicular pathway can alter the responses of many neurons in the ipsilateral IC (Massopust and Ordy, 1962, Amato et al., 1969, Syka and Popelar, 1984, Sun et al., 1989). The alterations include changes in frequency, amplitude and duration tuning (Suga, 2008), rate-level functions (Popelar et al., 2003), spatial sensitivity (Jen et al., 1998, Nakamoto et al., 2008), selectivity for harmonic complexes (Nakamoto et al., 2010) and stimulus-specific adaptation (Anderson and Malmierca, 2013). The AC projects directly to the lateral cortex1 (IClc), rostral cortex (ICrc), dorsal cortex (ICd) and central nucleus (ICc) of the ipsilateral IC (Saldaña et al., 1996, Winer et al., 1998), and it is assumed that these projections are directly responsible for many of the effects described above (Winer, 2005).

The AC can also excite or inhibit responses in the contralateral IC (Torterolo et al., 1998, Ma and Suga, 2001; unpublished observations). In guinea pigs, over two-thirds of ICc cells showed changes in sound-evoked activity as a result of electrical stimulation of the contralateral primary AC (Torterolo et al., 1998). The circuitry underlying these effects is not clear. The AC projects directly to the contralateral IC, but this projection is much smaller than the ipsilateral one, and terminates exclusively in the cortical areas of the contralateral IC (Bajo and Moore, 2005, Bajo et al., 2007, Coomes Peterson and Schofield, 2007). There is no evidence of a cortical projection to the contralateral ICc, so both the excitatory and inhibitory effects of the AC on the contralateral ICc must depend on a disynaptic or multisynaptic pathway.

Moore (1988) has shown that the contralateral IC contains the largest number of labeled cells (compared to other hindbrain nuclei) after injection of a retrograde tracer into the IC. Similar results in other species confirm the large number of cells in the commissural pathway, and studies with anterograde tracers demonstrate widespread terminations of the commissural pathway (reviewed by Saldaña and Merchan, 2005). Stimulation or suppression of the commissural pathway affects the majority of IC cells (Smith, 1992, Moore et al., 1998, Reetz and Ehret, 1999, Malmierca et al., 2003, Malmierca et al., 2005, Du et al., 2009), suggesting that inputs to the commissural pathway could have widespread effects in the contralateral IC. Furthermore, stimulation of the commissure leads to both excitation and inhibition of IC cells (Moore et al., 1998, Reetz and Ehret, 1999). The excitation and inhibition are thought to be mediated exclusively by glutamate and GABA (Smith, 1992, Moore et al., 1998). The majority of the commissural cells are believed to be glutamatergic, consistent with direct excitation of target cells. The remaining commissural cells are GABAergic, and presumably account for inhibition of commissural targets (González-Hernández et al., 1996, Hernández et al., 2006). It is possible that the large projection from the AC to the ipsilateral IC contacts commissural cells that project throughout the contralateral IC. Commissural cells in the ICc and ICd project to all parts of the contralateral IC and thus could convey cortical effects throughout the contralateral IC (Saldaña and Merchan, 2005). Another major subdivision of the IC, the IClc, also contains commissural cells, but apparently few of these project to the contralateral ICc (Malmierca et al., 2009) so they are less likely to relay cortical influences to the opposite side. Whether cortical axons contact excitatory or inhibitory commissural cells is unknown. Given the sizes of the corticocollicular pathway and the commissural pathway, a disynaptic pathway from AC to IC commissural cells could represent the largest route for one AC to excite or inhibit the contralateral IC. The present study was designed to identify connections consistent with this hypothesis. The results support the existence of primarily excitatory disynaptic pathways from auditory cortex to the contralateral IC and suggest that different IC subdivisions contribute to differing degrees.

Section snippets

Subjects

Tracing experiments were performed on 6 adult pigmented guinea pigs of either gender weighing 410–867 g (Elm Hill Breeding Laboratories, Chelmsford, MA, USA). Tissue from one additional animal was used for Western blot analysis. All procedures were approved by the Institutional Animal Care and Use Committee and administered following the National Institutes of Health guidelines for the care and use of laboratory animals. In accordance with these guidelines, all efforts were made to minimize the

Injections into the left auditory cortex

We injected FluoroRuby (FR) or fluorescein dextran (FD) across a wide swath of auditory cortex in order to label a large number of corticocollicular axons. Fig. 1A shows a surface view of a FluoroRuby injection in a representative case. FR was deposited along 3 parallel, tangential penetrations (arrows), extending ventrolaterally from the pseudosylvian sulcus (approaching, but not reaching, the rhinal sulcus; Fig. 1A). In the antero-posterior dimension, the deposits spread over a distance of

Discussion

The present study provides evidence that AC axons contact commissural cells in all IC subdivisions of the ipsilateral IC. In the ICc, the targets include both stellate and disc-shaped commissural cells. A large majority of the cortically contacted commissural cells are GAD-immunonegative. These results suggest that the ipsilateral corticocollicular pathway (which is excitatory) affects excitatory commissural cells and thus has primarily an excitatory effect on cells in the contralateral IC. We

Acknowledgments

We would like to thank Megan Storey-Workley for expert technical assistance and Dr. W. Chilian for use of his fluorescence macroscope. Dr. J. Mellott provided valuable comments on an early draft of the manuscript. Supported by NIH R01 DC04391 and 1 F32 DC010958.

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