Biased thalamic innervation onto the distinct subregion where dopamine receptor 1 is dominantly expressed in the caudal striatum.

In the ventral part of the caudal striatum, the direct and indirect pathway neurons are unevenly distributed, forming zones with a paucity of neurons with dopamine receptor 1 (D1R) or dopamine receptor 2 (D2R), referred as D1R- or D2R-poor zone (D1pz or D2pz, respectively). This contrasts with their uniform distribution in other striatal regions. A key question is whether D1pz and D2pz function as a unit or independently.

Orbitofrontal cortex influences dopamine dynamics associated with alloparental behavioral acquisition in female mice.

Maternal behaviors, which are crucial for the survival of mammalian infants, require the coordinated operation of multiple brain regions to process infant cues, make decisions, and execute motor plans. Although these processes likely demand higher cognitive functions, the prefrontal areas that regulate limbic parental programs remains poorly understood. Here, we show that the orbitofrontal cortex (OFC) excitatory projection neurons promote alloparental caregiving behaviors in female mice.

Activin B improves glucose metabolism via induction of Fgf21 and hepatic glucagon resistance.

Orchestrated hormonal interactions in response to feeding and fasting play a pivotal role in regulating glucose homeostasis. Here, we show that in obesity, the production of follistatin-like 3 (FSTL3), an endogenous inhibitor of Activin B, in adipose tissue is increased in both mice and humans. The knockdown of FSTL3 improves insulin sensitivity and glucose tolerance in diabetic obese db/db mice.

Whether or not to act is determined by distinct signals from motor thalamus and orbitofrontal cortex to secondary motor cortex.

"To act or not to act" is a fundamental decision made in daily life. However, it is unknown how the relevant signals are transmitted to the secondary motor cortex (M2), which is the cortical origin of motor initiation. Here, we found that in a decision-making task in male mice, inputs from the thalamus to M2 positively regulated the action while inputs from the lateral part of the orbitofrontal cortex (LO) negatively regulated it.

Neuron-non-neuron electrical coupling networks are involved in chronic stress-induced electrophysiological changes in lateral habenular neurons.

The lateral habenula (LHb) is a key brain structure that receives input from higher brain regions and regulates monoaminergic activity. LHb hyperactivity has been implicated in the pathophysiology of depression, but the electrophysiological mechanisms underlying this hyperactivity remain poorly understood. To address this issue, we investigated how chronic stress alters the firing properties of LHb neurons in a mouse model of chronic social defeat.

Protective effect of CK2 against endoplasmic reticulum stress in pancreatic β cells.

Unlabelled: Endoplasmic reticulum (ER) stress due to obesity or systemic insulin resistance is an important pathogenic factor that could lead to pancreatic β-cell failure. We have previously reported that CCAAT/enhancer-binding protein β (C/EBPβ) is highly induced by ER stress in pancreatic β cells. Moreover, its accumulation hampers the response of these cells to ER stress by inhibiting the induction of the molecular chaperone 78 kDa glucose-regulated protein (GRP78).

Gene Selection of Methionine-Dependent Melanoma and Independent Melanoma by Variable Selection Using Tensor Decomposition.

Methionine is an essential amino acid. Dietary methionine restriction is associated with decreased tumor growth in preclinical studies and extended lifespans in animal models. The mechanism by which methionine restriction inhibits tumor growth while sparing normal cells is not fully understood.

Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure in mice.

The presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review of the concepts of redox biology and its translational strategy. Glutathione (GSH) is the body's primary detoxifier and antioxidant, and its oxidized form (GSSG) has been considered as a marker of oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure in male mice by electrophilic modification of dynamin-related protein (Drp1).

An Indirect Pathway from the Rat Interstitial Nucleus of Cajal to the Vestibulocerebellum Involved in Vertical Gaze Holding.

The neural network, including the interstitial nucleus of Cajal (INC), functions as an oculomotor neural integrator involved in the control of vertical gaze holding. Impairment of the vestibulocerebellum (VC), including the flocculus (FL), has been shown to affect vertical gaze holding, indicating that the INC cooperates with the VC in controlling this function. However, a network between the INC and VC has not been identified.

Retinal pigment epithelium-specific ablation of GPx4 in adult mice recapitulates key features of geographic atrophy in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population, particularly the late-stage of dry AMD known as geographic atrophy (GA), lacks effective treatment options. Genetic mouse models of AMD have revealed the significance of impaired lipid metabolism and anti-oxidative capacity in early/intermediate stage of AMD, but remains unclear in GA that severely damages visual function. Here, to investigate the potential relevance of peroxidized lipids in RPE for late-stage dry AMD, GPx4 mice underwent subretinal injections of RPE-specific AAV-Cre vector or control AAV vector.

Stage-dependent role of interhemispheric pathway for motor recovery in primates.

Whether and how the non-lesional sensorimotor cortex is activated and contributes to post-injury motor recovery is controversial. Here, we investigated the role of interhemispheric pathway from the contralesional to ipsilesional premotor cortex in activating the ipsilesional sensorimotor cortex and promoting recovery after lesioning the lateral corticospinal tract at the cervical cord, by unidirectional chemogenetic blockade in macaques. The blockade impaired dexterous hand movements during the early recovery stage.

5' Transgenes drive leaky expression of 3' transgenes in Cre-inducible bi-cistronic vectors.

Molecular cloning techniques enabling contemporaneous expression of two or more protein-coding sequences provide an invaluable tool for understanding the molecular regulation of cellular functions. The Cre-lox system is used for inducing the expression of recombinant proteins encoded within a bi-/poly-cistronic cassette. However, leak expression of transgenes is often observed in the absence of Cre recombinase activity, compromising the utility of this approach.

Sensory-motor circuit is a therapeutic target for mice, a model of hereditary sensory and autonomic neuropathy 6.

Mutations in Dystonin (), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the () phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and phenotype is unresolved. mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of by Cre-mediated recombination.

Anterior cingulate cross-hemispheric inhibition via the claustrum resolves painful sensory conflict.

The anterior cingulate cortex (ACC) responds to noxious and innocuous sensory inputs, and integrates them to coordinate appropriate behavioral reactions. However, the role of the projections of ACC neurons to subcortical areas and their influence on sensory processing are not fully investigated. Here, we identified that ACC neurons projecting to the contralateral claustrum (ACC) preferentially respond to contralateral mechanical sensory stimulation.

Anterograde trans-neuronal labeling of striatal interneurons in relation to dopamine neurons in the substantia nigra pars compacta.

Recent advances in neural tracing have unveiled numerous neural circuits characterized by brain region and cell type specificity, illuminating the underpinnings of specific functions and behaviors. Dopaminergic (DA) neurons in the midbrain are highly heterogeneous in terms of gene and protein expression and axonal projections. Different cell types within the substantia nigra pars compacta (SNc) tend to project to the striatum in a cell-type-dependent manner characterized by specific topography.

Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.

Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents).

IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation.

Cytoplasmic aggregation of TDP-43 in neurons is a pathological feature common to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We demonstrate that the IκB kinase (IKK) complex promotes the degradation of cytoplasmic TDP-43 through proteasomes. While IKKβ is a major factor in TDP-43 degradation, IKKα acts as a cofactor, and NEMO functions as a scaffold for the recruitment of TDP-43 to the IKK complex.