Circuit Mechanisms Underlying the Segregation and Integration of Parallel Processing Streams in the Inferior Colliculus.

The lateral cortex of the inferior colliculus (LCIC) forms a nexus between diverse multisensory, motor, and neuromodulatory streams. Like other integration hubs, it contains repeated neurochemical motifs with distinct inputs: GABA-rich modules are innervated by somatosensory structures, while auditory inputs to the LCIC target the surrounding extramodular matrix. To investigate potential mechanisms of convergence between these input streams, we used laser photostimulation circuit mapping to interrogate local LCIC circuits in adult mice of both sexes and found that input patterns are highly dependent on cell type (GABAergic/non-GABAergic) and location (module/matrix). At the circuit level, these inputs yield a directional flow of local information, primarily from the matrix to the modules. Further, the two compartments were found to project to distinct targets in the midbrain and thalamus. These data show that, while connectional modularity in the LCIC gives rise to segregated input-output channels, local circuits provide the architecture for integration between these two streams.SIGNIFICANCE STATEMENT Modularity is a widespread motif across the brain involving the segregation of structures into discrete subregions based on dichotomies in neurochemical expression or connectivity. The inferior colliculus is one such modular structure, containing auditory-recipient matrix regions and GABA-rich modules that are innervated by somatosensory inputs. While modularity suggests segregation of processing streams, here we show that local circuits in the inferior colliculus connect the module and matrix regions, providing an avenue for integration of information across compartments.

Thalamocortical and Intracortical Inputs Differentiate Layer-Specific Mouse Auditory Corticocollicular Neurons.

Long-range descending projections from the auditory cortex play key roles in shaping response properties in the inferior colliculus. The auditory corticocollicular projection is massive and heterogeneous, with axons emanating from cortical layers 5 and 6, and plays a key role in directing plastic changes in the inferior colliculus. However, little is known about the cortical and thalamic networks within which corticocollicular neurons are embedded. Here, laser scanning photostimulation glutamate uncaging and photoactivation of channelrhodopsin-2 were used to probe the local and long-range network differences between preidentified layer 5 and layer 6 auditory corticocollicular neurons from male and female mice in vitro Layer 5 corticocollicular neurons were found to vertically integrate supragranular excitatory and inhibitory input to a substantially greater degree than their layer 6 counterparts. In addition, all layer 5 corticocollicular neurons received direct and large thalamic inputs from channelrhodopsin-2-labeled thalamocortical fibers, whereas such inputs were less common in layer 6 corticocollicular neurons. Finally, a new low-calcium/synaptic blockade approach to separate direct from indirect inputs using laser photostimulation was validated. These data demonstrate that layer 5 and 6 corticocollicular neurons receive distinct sets of cortical and thalamic inputs, supporting the hypothesis that they have divergent roles in modulating the inferior colliculus. Furthermore, the direct connection between the auditory thalamus and layer 5 corticocollicular neurons reveals a novel and rapid link connecting ascending and descending pathways.SIGNIFICANCE STATEMENT Descending projections from the cortex play a critical role in shaping the response properties of sensory neurons. The projection from the auditory cortex to the inferior colliculus is a massive, yet poorly understood, pathway emanating from two distinct cortical layers. Here we show, using a range of optical techniques, that mouse auditory corticocollicular neurons from different layers are embedded into different cortical and thalamic networks. Specifically, we observed that layer 5 corticocollicular neurons integrate information across cortical lamina and receive direct thalamic input. The latter connection provides a hyperdirect link between acoustic sensation and descending control, thus demonstrating a novel mechanism for rapid "online" modulation of sensory perception.