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Takemoto-Kimura, S.

Publications and source records attributed to Takemoto-Kimura, S..

3 recordsLinked to original sources

A preoptic circuit triggers rewarming from torpor

Torpor is an adaptive hypometabolic state that enables homeotherm to survive periods of energetic challenge. This strategy ranges from short bouts of daily torpor to prolonged hibernation. During torpor, animals markedly suppress metabolic rate, body temperature, heart rate, and respiration, while retaining the ability to rewarm. Torpor therefore comprises two critical transitions -entry into a hypometabolic state and active rewarming-both essential for organismal viability. Although neural mechanisms controlling torpor entry have begun to emerge, the circuits that initiate active rewarming and restore euthermia remain poorly defined. Here we identify corticotropin-releasing hormone (Crh)-expressing neurons in the anterodorsal preoptic area (ADP) as a key population for rewarming from fasting-induced torpor in mice. These neurons become active around natural rewarming and are selectively required to limit the depth and duration of torpor. Unlike pathways mediating acute cold defence, stress hyperthermia, or LPS-induced fever, this circuit is dedicated to promoting timely recovery to euthermia. Closed-loop optogenetic activation of ADPCrh neurons during torpor entry rapidly initiates rewarming, and thermographic recordings show that brown adipose tissue (BAT) thermogenesis precedes locomotor arousal. ADPCrh neurons are predominantly GABAergic and project monosynaptically to the lateral preoptic area, whose terminal activation is sufficient to increase body temperature and locomotor activity. Finally, we find robust activation of ADPCrh neurons during rewarming in a hibernator, suggesting conserved logic for exiting deep torpor. Together, our results define a discrete preoptic circuit that drives recovery from torpor and provide a framework for understanding and potentially controlling timely rewarming from profound hypothermia.

neuroscience↗

Cortical excitatory and inhibitory neuron deficits may underlie the cognitive and social impairments in a mouse model of schizophrenia with exonic Reln deletion

Reelin is an essential extracellular matrix glycoprotein involved in the formation of cortical layers and has been associated with several neuropsychiatric conditions, such as schizophrenia (SCZ). To explore its role in brain function and its potential involvement in SCZ, we developed a Reln heterozygous deletion (Relndel/+) mouse model that mimics a genetic deletion observed in a Japanese patient with SCZ. In previous studies, we demonstrated that Relndel/+ mice exhibit cognitive impairments in a visual discrimination test. Here, we found that Relndel/+ mice displayed impairments in social novelty recognition, while social preference remained intact. Immunohistochemical analyses revealed a significant decrease in the numbers of calcium/calmodulin-dependent protein kinase II (CaMKII)-positive glutamatergic pyramidal neurons, gamma-aminobutyric acid (GABA)-ergic interneurons, and parvalbumin (PV)-positive interneurons in the medial prefrontal cortex (mPFC) of Relndel/+ mice. Furthermore, Relndel/+ mice exhibited significant deficits in excitatory spine density and morphology, as well as a decrease number of PV boutons in the mPFC compared to wild-type (WT) mice. Finally, we demonstrated that injection of AAV-R36-Myc virus into the mPFC can improve social novelty impairments in Relndel/+ mice, but no effects on WT control. These findings indicate that Relndel/+ mice could be a valuable model for exploring the neurobiological mechanisms underlying cognitive and social impairments in SCZ. Futhermore, our results with AAV-R36-Myc also suggest the therapeutic potential of Reelin replacement, warranting further investigation as a possible treatment strategy for SCZ. HighlightsO_LIReelin deficiency disrupts social novelty, but not social preference, in Relndel/+ mice C_LIO_LIRelndel/+ mice serve as a novel model to investigate impairments of neuronal mechanisms on schizophrenia C_LIO_LIAAV-R36-myc injection rescues social novelty deficits in Relndel/+ mice C_LIO_LIReelin replacement therapy is a potential treatment for schizophrenia C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=143 HEIGHT=200 SRC="FIGDIR/small/666057v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1f4921aorg.highwire.dtl.DTLVardef@1a41b33org.highwire.dtl.DTLVardef@f5f2bcorg.highwire.dtl.DTLVardef@1134d8d_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

Remote control of neural function by X-ray-induced scintillation

Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), could effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively. Using injectable Ce:GAGG microparticles, we successfully activated and inhibited midbrain dopamine neurons in freely moving mice by X-ray irradiation, producing bidirectional modulation of place preference behavior. Ce:GAGG microparticles were non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level was sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables less invasive, wireless control of cellular functions at any tissue depth in living animals, expanding X-ray applications to functional studies of biology and medicine.

neuroscience↗