Biology subjects

Tanaka-Yamamoto, K.

Publications and source records attributed to Tanaka-Yamamoto, K..

3 recordsLinked to original sources

bioRxiv2026

Cerebellar induced VTA plasticity underlies chronic stress-induced depression-like behaviors

Synaptic regulation is a key mechanism underlying neural circuit homeostasis and plasticity. We previously showed that projections from the deep cerebellar nuclei (DCN) to the ventral tegmental area (VTAp-DCN neurons) contribute to depression-like behaviors following chronic restraint stress (RS), but the mechanisms by which these outputs induce downstream long-term functional changes remain unknown. Here, we show that chronic RS induces an activity-dependent reduction in vesicular glutamate transporter 2 (VGLUT2) expression in VTAp-DCN axons, resulting in decreased miniature excitatory postsynaptic current frequency in dorsolateral VTA dopaminergic neurons and reduced phasic dopamine release in the nucleus accumbens. Notably, VGLUT2 reduction temporally coincides with the emergence of depression-like behaviors. Consistent with this, targeted VGLUT2 overexpression in VTAp-DCN neurons rescues synaptic transmission and dopamine signaling and prevents depression-like behaviors following chronic RS. These findings reveal a stress-induced plasticity mechanism in the cerebellar-VTA circuit linking chronic stress to depression-like behaviors.

neuroscience↗

bioRxiv2021

Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus

The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in Parkinsons disease patients. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, input circuit and cellular profile in the STN remain largely unclear. Using advanced neuroanatomical techniques, we constructed a comprehensive connectivity map of the indirect and hyperdirect pathways in both the mouse and human STN. Our detailed circuit- and cellular-level connectivity revealed a topographically graded organization with three convergent types of indirect and hyperdirect-pathways. Furthermore, we identified two functional types of glutamatergic STN neurons (parvalbumin, PV +/- neurons) segregated with a topographical distribution. Glutamatergic PV+ STN neurons contribute to burst firing. We confirmed synaptic connectivity from indirect and hyperdirect pathways to both PV+ and PV-. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

neuroscience↗

bioRxiv2021

VTA-projecting cerebellar neurons mediate stress-dependent depression-like behavior

Although cerebellar alterations have been implicated in mental depression, the exact contribution of the cerebellum to depressive symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the chronic stress-induced development of depression-like behavior. The combination of adeno-associated virus-based circuit mapping and electrophysiological recording identified network connections from crus I to the VTA via the dentate nucleus (DN) of the deep cerebellar nuclei. Chronic chemogenetic activation of inhibitory Purkinje cells in crus I suppressed c-Fos expression in the DN and depression-like behavior, which were triggered by chronic stress application. Furthermore, specific inhibition of neurons in the DN that project to the VTA prevented stressed mice from showing depression-like behavior, whereas specific activation of these neurons alone triggered depression-like behavior that was comparable with the one triggered by chronic stress application. Our results indicate that the VTA-projecting cerebellar neurons proactively regulate depression-like behavior, raising the possibility that cerebellum may be an effective target for the prevention of depressive disorders.

neuroscience↗