Modular‐extramodular organization in developing multisensory shell regions of the mouse inferior colliculus

Abstract

The complex neuroanatomical connections of the inferior colliculus (IC) and its major subdivisions offer a juxtaposition of segregated processing streams with distinct organizational features. While the tonotopically layered central nucleus is well-documented, less is known about functional compartments in the neighboring lateral cortex (LCIC). In addition to a laminar framework, LCIC afferent-efferent patterns suggest a multimodal mosaic, consisting of a patchy modular network with surrounding extramodular domains. This study utilizes several neurochemical markers that reveal an emerging LCIC modular-extramodular microarchitecture. In newborn and post-hearing C57BL/6J and CBA/CaJ mice, histochemical and immunocytochemical stains were performed for acetylcholinesterase (AChE), nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), glutamic acid decarboxylase (GAD), cytochrome oxidase (CO), and calretinin (CR). Discontinuous layer 2 modules are positive for AChE, NADPH-d, GAD, and CO throughout the rostrocaudal LCIC. While not readily apparent at birth, discrete cell clusters emerge over the first postnatal week, yielding an identifiable modular network prior to hearing onset. Modular boundaries continue to become increasingly distinct with age, as surrounding extramodular fields remain largely negative for each marker. Alignment of modular markers in serial sections suggests each highlight the same periodic patchy network throughout the nascent LCIC. In contrast, CR patterns appear complementary, preferentially staining extramodular LCIC zones. Double-labeling experiments confirm that NADPH-d, the most consistent developmental modular marker, and CR label separate, nonoverlapping LCIC compartments. Determining how this emerging modularity may align with similar LCIC patch-matrix-like Eph/ephrin guidance patterns, and how each interface with, and potentially influence developing multimodal LCIC projection configurations is discussed.

Complex and spatially segregated auditory inputs of the mouse superior colliculus

“…7% in nBIC, 15% overall, Table ) (Dillingham et al . ), providing evidence that cell bodies of SGP‐projecting inhibitory neurons match the mediolateral axon trajectories (Fig. ).…”

“…Examples of double-labelled neurons are presented in Fig. 6B and C. Although the total number of neurons retrogradely labelled in the nBIC was higher than in the ECIC (1389 in nBIC vs. 1112 in ECIC, Table 3), the percentage of those neurons positive for GAD67 was larger in the ECIC when compared to the nBIC (27% in ECIC vs. 7% in nBIC, 15% overall, Table 3) (Dillingham et al 2017), providing evidence that cell bodies of SGP-projecting inhibitory neurons match the mediolateral axon trajectories (Fig. 5).…”

“…Moreover, retrogradely labelled neurons also positive for calretinin (although never also positive for GAD67; Dillingham et al . ) were distributed more equally throughout the nBIC and the ECIC regions (22% in ECIC vs . 30% in nBIC, Table ), a finding also consistent with the more even distribution of the excitatory axon trajectories (Fig.…”

Tonotopic and multisensory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging

“…74 In addition to GAD67, the calcium buffer parvalbumin (PV) is another marker for neurochemical modules 75 in the rat (Chernock et al 2004), while the calcium buffer calretinin (CR) shows a complementary 76 expression (i.e. in the extramodular region) in juvenile and early postnatal mice (Dillingham et al 2017). 77…”

Modularity in the Microcircuitry of the Mouse Inferior Colliculus Yields Dual Processing Streams for Auditory and Multisensory Information

“…The IC, a midbrain structure that is centrally positioned within the auditory system and is thought to serve as an integration hub, also exhibits modularity (Casseday et al, 2002). Specifically, the LCIC can be subdivided into modular regions characterized by dense staining for GAD67, PV, CO, AChE, and NADPH-d, and extramodular regions that are characterized by heavy calretinin labeling (Chernock et al, 2004;Stebbings et al, 2014;Lesicko et al, 2016;Dillingham et al, 2017).…”