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The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2 + administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural–functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2 + injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2 + transfer but not intra- or inter-hemispheric monosynaptic Mn2 + transport after Mn2 + injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural–functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies.

Despite the immense ongoing efforts to map brain functional connections and organizations with resting-state functional MRI (rsfMRI), the mechanisms governing the temporally coherent rsfMRI signals remain unclear. In particular, there is a lack of direct evidence regarding the morphological foundation and plasticity of these rsfMRI derived connections. In this study, we investigated the role of axonal projections in rsfMRI connectivity and its plasticity. Well-controlled rodent models of complete and posterior corpus callosotomy were longitudinally examined with rsfMRI at 7T in conjunction with intracortical EEG recording and functional MRI tracing of interhemispheric neuronal pathways by manganese (Mn(2+)). At post-callosotomy day 7, significantly decreased interhemispheric rsfMRI connectivity was observed in both groups in the specific cortical areas whose callosal connections were severed. At day 28, the disrupted connectivity was restored in the partial callosotomy group but not in the complete callosotomy group, likely due to the compensation that occurred through the remaining interhemispheric axonal pathways. This restoration - along with the increased intrahemispheric functional connectivity observed in both groups at day 28 - highlights the remarkable adaptation and plasticity in brain rsfMRI connections. These rsfMRI findings were paralleled by the intracortical EEG recording and Mn(2+) tracing results. Taken together, our experimental results directly demonstrate that axonal connections are the indispensable foundation for rsfMRI connectivity and that such functional connectivity can be plastic and dynamically reorganized atop the morphological connections.

Rodents share general anatomical, physiological and behavioral features in the central auditory system with humans. In this study, monaural broadband noise and pure tone sounds are presented to normal rats and the resulting hemodynamic responses are measured with blood oxygenation level-dependent (BOLD) fMRI using a standard spin-echo echo planar imaging sequence (without sparse temporal sampling). The cochlear nucleus (CN), superior olivary complex, lateral lemniscus, inferior colliculus (IC), medial geniculate body and primary auditory cortex, all major auditory structures, are activated by broadband stimulation. The CN and IC BOLD signal changes increase monotonically with sound pressure level. Pure tone stimulation with three distinct frequencies (7, 20 and 40 kHz) reveals the tonotopic organization of the IC. The activated regions shift from dorsolateral to ventromedial IC with increasing frequency. These results agree with electrophysiology and immunohistochemistry findings, indicating the feasibility of auditory fMRI in rats. This is the first fMRI study of the rodent ascending auditory pathway.

Rapid detection of deviant sounds is a crucial property of the auditory system because it increases the saliency of biologically important, unexpected sounds. The oddball paradigm in which a deviant sound is randomly interspersed among a train of standard sounds has been traditionally used to study this property in mammals. Currently, most human studies have only revealed the involvement of cortical regions in this property. Recently, several animal electrophysiological studies have reported that neurons in the inferior colliculus (IC) exhibit reduced responses to a standard sound but restore their responses at the occurrence of a deviant sound (i.e., stimulus-specific adaptation or SSA), suggesting that the IC may also be involved in deviance detection. However, by adopting an invasive method, these animal studies examined only a limited number of neurons. Although SSA appears to be more prominent in the external cortical nuclei of the IC for frequency deviant, a thorough investigation of this property throughout the IC using other deviants and efficient imaging techniques may provide more comprehensive information on this important phenomenon. In this study, blood-oxygen-level-dependent (BOLD) fMRI with a large field of view was applied to investigate the role of the IC in deviance detection. Two sound tokens that had identical frequency spectrum but temporally inverted profiles were used as the deviant and standard. A control experiment showed that these two sounds evoked the same responses in the IC when they were separately presented. Two oddball experiments showed that the deviant induced higher responses than the standard (by 0.41 ± 0.09% and 0.41 ± 0.10%, respectively). The most activated voxels were in the medial side of the IC in both oddball experiments. The results clearly demonstrated that the IC is involved in deviance detection. BOLD fMRI detection of increased activities in the medial side of the IC to the deviant revealed the highly adaptive nature of a substantial population of neurons in this region, probably those that belong to the rostral or dorsal cortex of the IC. These findings highlighted the complexity of auditory information processing in the IC and may guide future studies of the functional organizations of this subcortical structure.

Intensity is an important physical property of a sound wave and is customarily reported as sound pressure level (SPL). Invasive techniques such as electrical recordings, which typically examine one brain region at a time, have been used to study neuronal encoding of SPL throughout the central auditory system. Non-invasive functional magnetic resonance imaging (fMRI) with large field of view can simultaneously examine multiple auditory structures. We applied fMRI to measure the hemodynamic responses in the rat brain during sound stimulation at seven SPLs over a 72 dB range. This study used a sparse temporal sampling paradigm to reduce the adverse effects of scanner noise. Hemodynamic responses were measured from the central nucleus of the inferior colliculus (CIC), external cortex of the inferior colliculus (ECIC), lateral lemniscus (LL), medial geniculate body (MGB), and auditory cortex (AC). BOLD signal changes generally increase significantly (p0.001) with SPL and the dependence is monotonic in CIC, ECIC, and LL. The ECIC has higher BOLD signal change than CIC and LL at high SPLs. The difference between BOLD signal changes at high and low SPLs is less in the MGB and AC. This suggests that the SPL dependences of the LL and IC are different from those in the MGB and AC and the SPL dependence of the CIC is different from that of the ECIC. These observations are likely related to earlier observations that neurons with firing rates that increase monotonically with SPL are dominant in the CIC, ECIC, and LL while non-monotonic neurons are dominant in the MGB and AC. Further, the IC's SPL dependence measured in this study is very similar to that measured in our earlier study using the continuous imaging method. Therefore, sparse temporal sampling may not be a prerequisite in auditory fMRI studies of the IC.