Biology subjects

Chao, T.-H. H.

Publications and source records attributed to Chao, T.-H. H..

5 recordsLinked to original sources

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↗

bioRxiv2021

Chemogenetic activation of Locus Coeruleus Noradrenergic Neurons Modulates the Default Mode Network

The default mode network (DMN) of the brain is involved in cognition, emotion regulation, impulsivity, and balancing between internally and externally focused states. DMN dysregulation has been implicated in several neurological and neuropsychiatric disorders. In this study, we used functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and spectral fiber-photometry to investigate the selective neuromodulatory effect of norepinephrine (NE)-releasing noradrenergic neurons in the locus coeruleus (LC) on the DMN in mice. Chemogenetic-induced tonic LC-NE activity decreased cerebral blood volume (CBV) and glucose uptake, and increased synchronous low frequency fMRI activity within the frontal cortices of the DMN. Fiber-photometry results corroborated these findings, showing that LC-NE activation induced NE release, enhanced calcium-weighted neuronal spiking, and reduced CBV in the anterior cingulate cortex. These data suggest that LC-NE alters conventional stimulus-evoked coupling between neuronal activity and CBV in the frontal DMN. We also demonstrated that chemogenetic activation of LC-NE neurons strengthened functional connectivity within the frontal DMN, and this effect was causally mediated by reduced modulatory inputs from retrosplenial and hippocampal regions to the association cortices of the DMN.

neuroscience↗

bioRxiv2021

Spectral fiber-photometry derives hemoglobin-absorption changes for accurate measurement of fluorescent sensors

Fiber-photometry is an emerging technique for recording fluorescent sensor activity in the brain. However, significant hemoglobin-absorption artifacts in fiber-photometry data may be misinterpreted as sensor activity changes. Because hemoglobin exists in nearly every location in the brain and its concentration varies over time, such artifacts could impede the accuracy of many photometry recording results. Here we present a novel use of spectral photometry technique and propose computational methods to quantify photon absorption effects by using activity-independent fluorescence signals, which can be used to derive oxy- and deoxy-hemoglobin concentration changes. Following time-locked neuronal activation in vivo, we observed that a 20% increase in CBV contributes to about a 4% decrease in green fluorescence signal and a 2% decrease in red fluorescence signal. While these hemoglobin concentration changes are often temporally delayed than the fast-responding fluorescence spikes, we found that erroneous interpretation may occur when examining pharmacology-induced sustained activity changes, and in some cases, hemoglobin-absorption could flip the GCaMP signal polarity. We provided hemoglobin-based correction methods to restore fluorescence signals across spectra and compare our results against the commonly used regression approach. We also demonstrated the utility of spectral fiber-photometry for delineating brain regional differences in hemodynamic response functions. HighlightsO_LIHemoglobin-absorption compromises fiber-photometry recording in vivo C_LIO_LISpectral photometry allows quantification of hemoglobin concentration changes for correction C_LIO_LIThe proposed platform allows measuring regional differences in neurovascular transfer function C_LI

neuroscience↗

bioRxiv2021

Simultaneous fMRI and fast-scan cyclic voltammetry bridges oxygenation and neurotransmitter dynamics across spatiotemporal scales

The vascular contributions of neurotransmitters to the hemodynamic response are gaining more attention in neuroimaging studies, as many neurotransmitters are vasomodulatory. To date, well-established electrochemical techniques that detect neurotransmission in high magnetic field environments are limited. Here, we propose an experimental setting enabling simultaneous fast-scan cyclic voltammetry (FSCV) and blood oxygenation-dependent functional magnetic imaging (BOLD fMRI) to measure both local tissue oxygen and dopamine responses, and global BOLD changes, respectively. By using MR-compatible materials and the proposed data acquisition schemes, FSCV detected physiological analyte concentrations with high spatiotemporal resolution inside of a 9.4 T MRI bore. We found that tissue oxygen and BOLD correlate strongly, and brain regions that encode dopamine amplitude differences can be identified via modeling simultaneously acquired dopamine FSCV and BOLD fMRI time-courses. This technique provides complementary neurochemical and hemodynamic information and expands the scope of studying the influence of local neurotransmitter release over the entire brain.

neuroscience↗

bioRxiv2020

Dysregulation of hippocampal adult-born immature neurons disrupts a brain-wide network for spatial memory

Mounting evidence suggests that cognitive deficits associated with various neurological disorders may arise in part from a small population of dysregulated adult-born neurons in the dentate gyrus (DG). How these dysregulated adult-born neurons contribute to brain-wide network maladaptation and subsequent cognitive deficits remains unknown. Using an established mouse model with a small number of time-stamped dysregulated adult-born immature neurons and spatial memory deficits, we performed resting state functional magnetic resonance imaging and found that approximately 500 deficient immature neurons (<0.1% of total DG granule neurons) are sufficient to induce a significant decrease in the functional connectivity between DG and insular cortex (IC), two brain regions without direct anatomical connections. Furthermore, using a combination of rabies-based retrograde tracing and in vivo fiber photometry recording, we demonstrated that dysregulated adult-born neurons induce aberrant activity and synchrony in local hippocampal CA3 and CA1 regions, as well as distal medial-dorsal thalamus and IC regions during a spatial memory process. These results suggest that a few hundred dysregulated adult-born immature neurons can impact brain-wide network dynamics across several anatomically discrete regions and collectively contribute to impaired cognitive functions.

neuroscience↗