Abstract
Guidance errors and unrefined neural map configurations appear linked to certain neurodevelopmental conditions, including autism spectrum disorders. Deficits in specific multisensory tasks that require midbrain processing are highly predictive of cognitive and behavioral phenotypes associated with such syndromes. The lateral cortex of the inferior colliculus (LCIC) is a shell region of the mesencephalon that integrates converging information from multiple levels and modalities. Mature LCIC sensory maps are discretely-organized, mimicking its compartmental micro-organization. Intermittent modular domains receive patchy somatosensory connections, while inputs of auditory origin terminate in the encompassing extramodular matrix.Eph-ephrin signaling mechanisms instruct comparable topographic arrangements in a variety of other systems. Whether Eph-ephrin interactions also govern the assembly of LCIC multimodal maps remains unaddressed. Previously, we identified EphA4 and ephrin-B2 as key mediators, with overlapping expression patterns that align with emerging LCIC modules. Here, we implicate another member of this guidance family, ephrin-B3, and quantify its transient expression with respect to neurochemically-defined LCIC compartments. Multiple-labeling studies in GAD67-GFP knock-in mice reveal extramodular ephrin-B3 expression, complementary to that of EphA4 and ephrin-B2. This distinctive pattern sharpens over the early postnatal period (birth to P8), prior to ephrin-B3 downregulation once multimodal LCIC inputs are largely segregated (P12). Channel-specific sampling of LCIC ROIs show ephrin-B3 signal periodicities that are out-of-phase with glutamic acid decarboxylase (GAD;modular marker) signal fluctuations, and match calretinin (CR) waveforms (matrix marker). Taken together, the guidance mosaic registry with emerging LCIC compartments and its interfacing afferent streams suggest a prominent role for Eph-ephrins in ordering behaviorally significant multisensory midbrain networks.
Highlights
One important function of the midbrain is the integration of multisensory cues critical for reflexive and orientation behaviors (Gruters and Groh, 2012; Louthan et al, 2020)
Transient lateral cortex of the inferior colliculus (LCIC) Ephrin-B3 Matrix Expression documented (Triplett et al, 2012), with activity driving the registry of auditory (King et al, 1988; Knudsen and Brainard, 1991) and visual cortical maps for retinocollicular inputs, while topographic projections from primary somatosensory cortex rely upon positional cues provided by complementary ephrin-A/EphA guidance gradients (Rashid et al, 2005; Miller et al, 2006)
Ephrin-B3 is present at P0, largely localized to the LCIC, and most heavily concentrated in dorsal aspects (Figures 1B,C)
Summary
One important function of the midbrain is the integration of multisensory cues critical for reflexive and orientation behaviors (Gruters and Groh, 2012; Louthan et al, 2020). LCIC efferent systems appear to be compartmentally organized, with the extramodular matrix projecting bilaterally to other IC subdivisions and the SC, while modular domains, in turn, target the medial division of the medial geniculate body and the closely associated posterior limitans and posterior intralaminar nuclei. Such an arrangement allows for routing of matrix auditory processing to appropriate midbrain targets, while providing a means for multisensory integration within the LCIC (i.e., modules), before its transmission on to higher multimodal centers. Potential Eph-ephrin influences in establishing multisensory LCIC circuits, as well as their role in instructing contrasting neural map features (continuous vs discrete) in neighboring IC subdivisions during an early critical period are discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
