Biology subjects

Osakada, F.

Publications and source records attributed to Osakada, F..

5 recordsLinked to original sources

bioRxiv2024

Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPR{varepsilon}) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPR{varepsilon} by increased progesterone during pregnancy enhanced maternal insulin resistance through the production of prostaglandins, thereby efficiently providing glucose to embryos. The offspring of mPR{varepsilon}-deficient mothers exhibited metabolic dysfunction, whereas mPR{varepsilon}-deficient mothers with high-fat-diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo, and suggest that mPR{varepsilon} modulators could be developed to treat pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/609823v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1ecd968org.highwire.dtl.DTLVardef@b5492aorg.highwire.dtl.DTLVardef@1d692ecorg.highwire.dtl.DTLVardef@47de8a_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2024

Layer Va neurons, as major presynaptic partners of corticospinal neurons, play critical roles in skilled movements

Corticospinal neurons (CSNs) are located in the cortex and projecting into the spinal cord. The activation of CSNs, which is associated with skilled motor behaviors, induces the activation of interneurons in the spinal cord. Eventually, motor neuron activation is induced by corticospinal circuits to coordinate muscle activation. Therefore, elucidating how the activation of CSNs in the brain is regulated is necessary for understanding the roles of CSNs in skilled motor behaviors. However, the presynaptic partners of CSNs in the brain remain to be identified. Here, we performed transsynaptic rabies virus-mediated brain-wide mapping to identify presynaptic partners of CSNs (pre-CSNs). We found that pre-CSNs are located in all cortical layers, but major pre-CSNs are located in layer Va. A small population of pre-CSNs are also located outside the cortex, such as in the thalamus. Inactivation of layer Va neurons in Tlx3-Cre mice results in deficits in skilled reaching and grasping behaviors, suggesting that, similar to CSNs, layer Va neurons are critical for skilled movements. Finally, we examined whether the connectivity of CSNs is altered after spinal cord injury (SCI). We found that unlike connections between CNSs and postsynaptic neurons, connections between pre-CSNs and CSNs do not change after SCI.

neuroscience↗

bioRxiv2023

Asymmetric cortical projections to striatal direct and indirect pathways distinctly control actions

The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do so vice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry. In BriefKlug, Yan et al. employed a modified rabies system in combination with slice physiology, optogenetics and behavioral tests to reveal that pathway-specific corticostriatal subcircuits distinctly control actions. HighlightsO_LIOne-third of the excitatory inputs to D1-SPNs project to D2-SPNs, while two-third of the excitatory inputs to D2-SPNs also target D1-SPNs C_LIO_LIActivation of D1-SPN projecting cortical neurons triggers behavioral effects in line with postsynaptic striatal direct pathway activation C_LIO_LIActivation of D2-SPN projecting cortical neurons causes behavioral effects similar with co-activation of both direct and indirect pathways C_LIO_LICorticostriatal subcircuits control actions in a brain-region and pathway-specific manner C_LI

neuroscience↗

bioRxiv2023

Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids

Studying the non-human primate (NHP) brain is required for the translation of rodent research to humans, but remains a challenge for molecular, cellular, and circuit-level analyses in the NHP brain due to the lack of in vitro NHP brain system. Here, we report an in vitro NHP cerebral model using marmoset (Callithrix jacchus) embryonic stem cell-derived cerebral assembloids (CAs) that recapitulate inhibitory neuron migration and cortical network activity. Cortical organoids (COs) and ganglionic eminence organoids (GEOs) were induced from cjESCs and fused to generate CAs. GEO cells expressing the inhibitory neuron marker LHX6 migrated toward the cortical side of CAs. COs developed their neural activity from a synchronized pattern to an unsynchronized pattern as COs matured. CAs showed mature neural activity with an unsynchronized pattern. The marmoset assembloid system will provide an in vitro platform for the NHP neurobiology and facilitate translation into humans in neuroscience research, regenerative medicine, and drug discovery.

neuroscience↗

bioRxiv2022

Posteromedial cortical networks encode visuomotor prediction errors.

Predicting future events based on internal models is essential for animal survival. Predictive coding postulates that errors between prediction and observation in lower-order areas update predictions in higher-order areas through the hierarchy. However, it is unclear how predictive coding is implemented in the hierarchy of the brain. Herein, we report the neural mechanism of the hierarchical processing and transmission of bottom-up prediction error signals in the mouse cortex. Ca2+ imaging and electrophysiological recording in virtual reality revealed responses to visuomotor mismatches in the retrosplenial, dorsal visual, and anterior cingulate cortex. These mismatch responses were attenuated when mismatches became predictable through experience. Optogenetic inhibition of bottom-up signals reduced a behavioral indicator for prediction errors. Moreover, cellular-level mismatch responses were modeled by Bayesian inference using a state-space model. This study demonstrates hierarchical circuit organization underlying prediction error propagation, advancing the understanding of predictive coding in sensory perception and learning in the brain. O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/504075v2_ufig1.gif" ALT="Figure 1"> View larger version (82K): org.highwire.dtl.DTLVardef@1f03960org.highwire.dtl.DTLVardef@46df08org.highwire.dtl.DTLVardef@dc97ccorg.highwire.dtl.DTLVardef@7200ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗