Hsu, L.-M. | Search bioRxiv

bioRxiv2024

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation

While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinsons disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using function magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examinations of cell-type specific STN feed-forward neural activity. Unilateral STN optogenetic stimulation elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, these manipulations effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetically induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS.

neuroscience↗

bioRxiv2022

Neuronal dynamics of the default mode network and anterior insular cortex: Intrinsic properties and modulation by salient stimuli

The default mode network (DMN) is closely associated with self-referential mental functions and its dysfunction is implicated in many neuropsychiatric disorders. However, the neurophysiological properties and task-based functional organization of the rodent DMN are poorly understood, limiting its translational utility. Here, we combine fiber-photometry with fMRI and computational modeling to characterize dynamics of putative rodent DMN nodes and their interactions with the anterior insular cortex (AI) of the salience network. We reveal neuronal activity changes in AI and DMN nodes prior to fMRI-derived DMN activations and uncover cyclical transition patterns between spatiotemporal neuronal activity states. Finally, we demonstrate that salient oddball stimuli suppress the DMN and enhance AI neuronal activity, and that the AI causally inhibits the retrosplenial cortex, a prominent DMN node. These findings elucidate previously unknown properties regarding the neurobiological foundations of the rodent DMN and its modulation by salient stimuli, paving the way for future translational studies. HighlightsO_LIConcurrent measurement of neuronal (GCaMP) and fMRI signals in retrosplenial, cingulate, prelimbic, and anterior insula cortices C_LIO_LIGCaMP signals reveal neuronal antagonism between AI and fMRI-derived DMN activation and deactivation C_LIO_LIGCaMP signals reveal salient oddball stimuli-induced suppression of prelimbic, cingulate and retrosplenial cortices, and activation of anterior insular cortex C_LIO_LIAnterior insular cortex causally inhibits retrosplenial cortex during processing of salient oddball stimuli C_LIO_LIFindings delineate neurofunctional organization of the rodent DMN and provide a more informed model for translational studies C_LI

neuroscience↗