Fiber Photometry publications

To navigate real-world listening conditions, the auditory system relies on the integration of multiple sources of information. However, to avoid inappropriate cross-talk between inputs, highly connected neural systems need to strike a balance between integration and segregation. Here, we develop a novel approach to examine how repeated neurochemical modules in the mouse inferior colliculus lateral cortex (LC) allow controlled integration of its multimodal inputs. The LC had been impossible to study via imaging because it is buried in a sulcus. Therefore, we coupled two-photon microscopy with the use of a microprism to reveal the first-ever sagittal views of the LC to examine neuronal responses with respect to its neurochemical motifs under anesthetized and awake conditions. This approach revealed marked differences in the acoustic response properties of LC and neighboring non-lemniscal portions of the inferior colliculus. In addition, we observed that the module and matrix cellular motifs of the LC displayed distinct somatosensory and auditory responses. Specifically, neurons in modules demonstrated primarily offset responses to acoustic stimuli with enhancement in responses to bimodal stimuli, whereas matrix neurons showed onset response to acoustic stimuli and suppressed responses to bimodal stimulation. Thus, this new approach revealed that the repeated structural motifs of the LC permit functional integration of multimodal inputs while retaining distinct response properties.

Autism spectrum disorder (ASD) is often associated with social communication impairments and specific sound processing deficits, for example, problems in following speech in noisy environments. To investigate underlying neuronal processing defects located in the auditory cortex (AC), we performed two-photon Ca 2+ imaging in FMR1 ( fragile X messenger ribonucleoprotein 1 ) knock-out (KO) mice, a model for fragile X syndrome (FXS), the most common cause of hereditary ASD in humans. For primary AC (A1) and the anterior auditory field (AAF), topographic frequency representation was less ordered compared with control animals. We additionally analyzed ensemble AC activity in response to various sounds and found subfield-specific differences. In A1, ensemble correlations were lower in general, while in secondary AC (A2), correlations were higher in response to complex sounds, but not to pure tones. Furthermore, sound specificity of ensemble activity was decreased in AAF. Repeating these experiments 1 week later revealed no major differences regarding representational drift. Nevertheless, we found subfield- and genotype-specific changes in ensemble correlation values between the two times points, hinting at alterations in network stability in FMR1 KO mice. These detailed insights into AC network activity and topography in FMR1 KO mice add to the understanding of auditory processing defects in FXS.

The auditory cortex (AC) modulates the activity of upstream pathways in the auditory brainstem via descending (corticofugal) projections. This feedback system plays an important role in the plasticity of the auditory system by shaping response properties of neurons in many subcortical nuclei. The majority of layer (L) 5 corticofugal neurons project to the inferior colliculus (IC). This corticocollicular (CC) pathway is involved in processing of complex sounds, auditory-related learning, and defense behavior. Partly due to their location in deep cortical layers, CC neuron population activity patterns within neuronal AC ensembles remain poorly understood. We employed two-photon imaging to record the activity of hundreds of L5 neurons in anesthetized as well as awake animals. CC neurons are broader tuned than other L5 pyramidal neurons and display weaker topographic order in core AC subfields. Network activity analyses revealed stronger clusters of CC neurons compared to non-CC neurons, which respond more reliable and integrate information over larger distances. However, results obtained from secondary auditory cortex (A2) differed considerably. Here CC neurons displayed similar or higher topography, depending on the subset of neurons analyzed. Furthermore, specifically in A2, CC activity clusters formed in response to complex sounds were spatially more restricted compared to other L5 neurons. Our findings indicate distinct network mechanism of CC neurons in analyzing sound properties with pronounced subfield differences, demonstrating that the topography of sound-evoked responses within AC is neuron-type dependent.