Divergent and point-to-point connections in the commissural pathway between the inferior colliculi

Abstract

The commissure of the inferior colliculus interconnects the left and right sides of the auditory midbrain and provides the final opportunity for interaction between the two sides of the auditory pathway at the subcortical level. Although the functional properties of the commissure are beginning to be revealed, the topographical organization of its connections is unknown. A combination of neuroanatomical tracing studies, 3D reconstruction, and neuronal density maps was used to study the commissural connections in rat. The results demonstrate that commissural neurons in the central nucleus of the inferior colliculus send a divergent projection to the equivalent frequency-band laminae in the central nucleus and dorsal and lateral cortices on the opposite side. The density of this projection, however, is weighted toward a point that matches the position of the tracer injection; consistent with a point-to-point emphasis in the wiring pattern. In the dorsal cortex of the inferior colliculus there may be two populations of neurons that project across the commissure, one projecting exclusively to the frequency-band laminae in the central nucleus and the other projecting diffusely to the dorsal cortex. Neurons in the lateral cortex of the inferior colliculus make only a very weak contribution to the commissural pathway. The point-to-point pattern of connections permits interactions between specific regions of corresponding frequency-band laminae, whereas the divergent projection pattern could subserve integration across the lamina.

Figure 1

A: Photomicrograph showing two injections into the same lamina of the IC (case 279). The FD-BDA injection is confined to the DCIC, whereas the TRD injection is located in the CNIC. The BF at the injection sites was 10–10.5 kHz. Note the typical V-shaped plexus of intrinsic axons with a central wing located in the CNIC that extends into the DCIC and a lateral wing in the lateral cortex. The vertex of the plexus marks the border between the CNIC and the LCIC. B: Anterogradely labeled axons and retrogradely labeled neurons on the side contralateral to the injections in A. C: Camera lucida drawings of the retrogradely labeled neurons originating from the TDR and FD-BDA injections marked in red and black, respectively, at different rostrocaudal levels of the IC. Boxed area in the most caudal section is the area shown in B. D: High-magnification photograph of boxed area in the caudalmost section in C. Red arrows point to TRD-labeled neurons and black arrows to FD-BDA-labeled neurons. Scale bars = 250 μm in B (applies to A,B); 50 μm in D. [Color figure can be viewed in the online issue, which is available at http://www.interscience.wiley.com.]

Figure 2

3D reconstruction of the injection sites for two injections in the same animal (case 74) seen from the back (A), top (B), and lateral (C) sides of the IC. D: 3D reconstruction of the locations of all retrogradely labeled cells originating from the injections. E: Grid of ∼150-μm² squares used to produce the neuronal density map of the TRD retrogradely labeled neurons overlain with the grid. F,G: Histograms of the neuronal distribution across the x and y axes, respectively, of the grid used to generate the density map (cf. E). Note that only red neurons are labeled in the contralateral IC (D) and that the histograms (F,G) show a distinct peak in the number of labeled neurons in both the x and the y axes. CNIC borders, here and elsewhere, are denoted by the solid white line and are based on the cytoarchitectural scheme of the rat (Faye-Lund and Osen,; Loftus et al.,; Malmierca et al.,1993). Scale bar = 1 mm. [Color figure can be viewed in the online issue, which is available at http://www.interscience.wiley.com.]

Figure 3

3D reconstructions of the injection sites (left column) and the resulting labeled neurons (right column) in the contralateral ICs derived from injections in three cases. Top parts of each panel show transverse views; bottom parts of each panel show horizontal views. A: Case 279 (see also Fig. 4). B: Case 78 (see also Fig. 5). C: Case 35 (see also Fig. 6). Scale bar = 1 mm. [Color figure can be viewed in the online issue, which is available at http://www.interscience.wiley.com.]

Figure 4

Case 279. A: Density maps for TRD-labeled neurons in the transverse, horizontal, and sagittal projections. B: Similar projections for the FD-BDA-labeled neurons, following the injections shown in Figure 3A. C,D: Distribution histograms of the TRD- and FD-BDA-labeled neurons along the x and y axes of the grid (cf. Fig. 2, for clarity not shown). All histograms show an approximately normal distribution, with a distinct peak of neurons. In all projections, the distributions of neurons labeled by the two injections are significantly different. This is particularly evident along the y axis of the transverse and sagittal projections. P values show the outcome of t-tests comparing the distributions in each histogram. Scale bar = 1 mm. [Color figure can be viewed in the online issue, which is available at http://www.interscience.wiley.com.]

Figure 5

Case 78. Density maps for TRD- and FD-BDA-labeled neurons in the transverse, horizontal, and sagittal projections following the injections shown in Figure 3B. Details for A–D as for Figure 4. Scale bar = 1 mm. [Color figure can be viewed in the online issue, which is available at http://www.interscience.wiley.com.]

Figure 6

Case 35. A,B: Density maps for TRD- and FD-BDA-labeled neurons in the transverse, horizontal, and sagittal projections following injections shown in Figure 3C. Details for A–D as for Figure 4. Note the overlap in the distributions of the two populations of labeled neurons. Scale bar = 1 mm. [Color figure can be viewed in the online issue, which is available at http://www.interscience.wiley.com.]

Figure 7

Schematic wiring diagrams of the commissural connections summarizing the main findings of the study. A: In the CNIC, the retrograde labeling of neurons demonstrates that an injection into one point on the lamina (dotted circle, left IC) retrogradely labels neurons over the whole extent of the contralateral lamina, consistent with a divergent pattern of connections (thin arrows). Anterograde labeling also supports a divergent projection, insofar as a point injection into the CNIC results in a V-shaped axonal plexus that covers most of the CNIC lamina and extends into the cortices as previously shown (gray free-form shape; Malmierca et al.,; Saldaña and Merchán,1992). However, the density of the projection is centered on a point matching the position of the tracer injection. This result is consistent with a point-to-point-weighted wiring pattern (thick arrow). The coexistence of divergent and point-to-point projections suggests two functionally different systems of commissural connections, but from current evidence it is not possible to tell whether they are mediated by a single population or different cell populations. B: Our results suggest that two populations of neurons in the DCIC could contribute to the commissural projection to the contralateral IC: one population projects diffusely to the DCIC (solid squares), whereas the other projects to the frequency-band laminae in the CNIC in a tonotopic manner (open squares).