Biology subjects

Yuan, T.-F.

Publications and source records attributed to Yuan, T.-F..

3 recordsLinked to original sources

bioRxiv2026

Repetitive transcranial magnetic stimulation targeting motor cortical region induces cell-type-specific transcriptional reprogramming and behavioral recovery in non-human primate model of Rett syndrome

Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the MECP2 gene, currently lacks effective treatments. The motor cortex is a pivotal hub in RTT and autism spectrum disorders, and its impairments contribute to motor, social, and cognitive deficits. Here we examined the effects of repetitive transcranial magnetic stimulation (rTMS) targeting motor area in non-human primate of RTT (MECP2-mutant monkey) and investigated neuromolecular basis underlying therapeutic effects. We identified a new treatment target, ventral premotor cortex (PMv), for RTT and found that following a 20-day rTMS course, several behavioral and functional connectivity measures showed directional changes. Neuroimaging analyses confirmed that rTMS induced reorganization of large-scale functional connectivity with enhanced functional integration between the somatomotor and the salience networks and normalized coupling between the motor cortex and both the thalamus and the anterior cingulate cortex. Notably, single-nucleus RNA sequencing revealed that rTMS triggered cell-type-specific transcriptional reprogramming: it rescued pathological hyperactivity of excitatory neurons by restoring the expression and regulatory networks of immediate early genes (e.g., FOS, EGR1) and corrected dysregulated intercellular signaling (e.g., NRG, WNT). These findings indicate that targeting motor cortical areas with brain stimulation may treat RTT, which warrants further clinical validation.

neuroscience↗

bioRxiv2024

Hijacking a dedicated entorhinal-hippocampal extinction circuit to remove traumatic memory

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging due to the fragile nature of fear extinction, for which ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells suffice fear extinction. Gamma entrainment of vCA1 by deep brain stimulation (DBS) or noninvasive transcranial alternating current stimulation (tACS) of LEC persistently enhances the PV-IN activity in vCA1, thereby promoting fear extinction. These results demonstrate that the LEC-vCA1 pathway forms a top-down motif to empower low gamma-band oscillations that facilitate fear extinction. Finally, application of low gamma DBS and tACS to a mouse model with persistent PTSD shows potent efficacy, suggesting that the dedicated LEC-vCA1 pathway can be hijacked for therapy to remove traumatic memory trace. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/593830v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@ca6768org.highwire.dtl.DTLVardef@4ae574org.highwire.dtl.DTLVardef@11e4ff5org.highwire.dtl.DTLVardef@1136cc2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

A cingulate-hippocampal circuit mediates early depressive symptoms in Alzheimer's disease

AbstractDepressive symptoms are prevalent and precedes cognitive decline in Alzheimers disease (AD), which worsen the clinical outcome and severely challenge the life quality of the patients. However, the neural circuitry mediating mood disturbance in AD remains elusive. Here we report that the glutamatergic projection from the anterior cingulate cortex (ACC) to the ventral hippocampal CA1 (vCA1) acts as the neural substrate of depressive symptoms in AD. We systemically mapped axonal projection in early stage of 5xFAD mice (3 months), which accompanies depressive- like behavior in these animals and identified reduced axonal projection from ACC to vCA1. This is in accordance with reduced axonal calcium signals detected with in vivo fiber photometry. Chemogenetic or optogenetic reversal of ACC-vCA1 circuitry activity efficiently ameliorated the depressive-like behaviors as well as cognitive impairment in 5xFAD mice. We further identified the synaptic molecules neuregulin-1 (Nrg1) as one vital signal regulating the synaptic glutamate transmission from the ACC to the vCA1. Collectively, these results indicated ACC-vCA1 as a critical pathway that regulates emotional states in Alzheimer disease. Targeting cingulate cortices with brain stimulation may treat depression in AD.

neuroscience↗