TRPA1 as a O sensor detects microenvironmental hypoxia in the mice anterior cingulate cortex.

Transient receptor potential ankyrin 1 (TRPA1) is a member of the TRP channel family and is expressed in peripheral and central nervous systems. In the periphery, TRPA1 senses cold and pain. However, the functions of TRPA1 in the CNS are unclear.

Eye movement activity in normal human fetuses between 24 and 39 weeks of gestation.

Rapid eye movement (REM) sleep occurs throughout a relatively large proportion of early development, and normal REM activity appears to be required for healthy brain development. The eye movements (EMs) observed during REM sleep are the most distinctive characteristics of this state. EMs are used as an index of neurological function postnatally, but no specific indices of EM activity exist for fetuses.

Glycine plays a crucial role as a co-agonist of NMDA receptors in the neuronal circuit generating body movements in rat fetuses.

Neuronal circuits generating fetal movements in mammals are localized in the brainstem and the spinal cord. It has been shown that glycine plays an important role through the strychnine-sensitive glycine receptors in these circuits. However, the role of glycine as the NMDA receptor co-agonist in fetal period is not fully understood.

KCC2-mediated regulation of respiration-related rhythmic activity during postnatal development in mouse medulla oblongata.

GABA acts as inhibitory neurotransmitter in the adult central nervous system but as excitatory neurotransmitter during early postnatal development. This shift in GABA's action from excitation to inhibition is caused by a decrease in intracellular chloride concentration ([Cl(-)]i), which in turn is caused by changes in the relative expression levels of the K(+)-Cl(-) co-transporter (KCC2) and the Na(+), K(+)-2Cl(-) co-transporter (NKCC1) proteins. Previous studies have used slices containing the medullary pre-Bötzinger complex (pre-BötC) to record respiration-related rhythmic activity (RRA) from the hypoglossal nucleus (12 N).

Orexin-neuromodulated cerebellar circuit controls redistribution of arterial blood flows for defense behavior in rabbits.

We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray.

Imaging of neural ensemble for the retrieval of a learned behavioral program.

The encoding of long-term associative memories for learned behaviors is a fundamental brain function. Yet, how behavior is stably consolidated and retrieved in the vertebrate cortex is poorly understood. We trained zebrafish in aversive reinforcement learning and measured calcium signals across their entire brain during retrieval of the learned response.

Ontogeny of Cl- homeostasis in mouse hypoglossal nucleus.

We tested the immunoreactivity of KCC2 using KCC2 antibody in the developmental mouse medulla. Age-dependent changes in immunoreactivity were remarkable in the hypoglossal nucleus, and interestingly, the immunoreactivity in the hypoglossal nucleus relative to the dorsal vagal nucleus at P0 appeared to be higher than that of P7. Thus Cl(-) homeostasis in the hypoglossal nucleus might be differentially regulated in the developmental stage.

Adrenaline modulates on the respiratory network development.

Adrenaline regulates respiratory network, however, adrenergic contribution to the developing respiratory center has not well studied. Adrenaline application on embryonic day 17 medulla-spinal cord block preparations abolished non-respiratory activity and enhanced respiratory frequency. Phentolamine application on neonatal brainstem-spinal cord preparations that produced stable neonatal respiration resulted in respiratory destabilization.

Central respiratory failure in a mouse model depends on the genetic background of the host.

To define the mechanisms of human congenital central respiratory failure, we are examining gene-deficient mice with central respiratory failure. However, the influence of the genetic background of the mice may play an important role in the phenotype of the mice. Therefore, we examined developmental respiratory adaptation in several mouse strains.

Loss of pre-inspiratory neuron synchroneity in mice with DSCAM deficiency.

Down syndrome cell adhesion molecule (DSCAM) is a neural adhesion molecule that plays diverse roles in neural development. We disrupted the Dscam locus in mice and found that the null mutants (Dscam (-/-)) died within 24 hours after birth. Whole body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants.

Respiratory activity of the neonatal dorsolateral pons in vitro.

The lateral and medial parabrachial and the Kölliker-Fuse nuclei (NPB/KF) are well known respiratory modulating centers in adulthood, but their role in neonates is largely unknown. We examined the role of the NPB/KF using hemi-sectioned pons-brainstem-spinal cord preparations in neonatal rats. Electrical stimulation applied at various intensities and delays in relation to the onset of spontaneous inspiratory C4 bursts, evoked transient depression or termination of C4 activity.

DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death.

Down syndrome cell adhesion molecule (DSCAM) is a neural adhesion molecule that plays diverse roles in neural development. We disrupted the Dscam locus in mice and found that the null mutants (Dscam(-/-)) died within 24 h after birth. Whole-body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants.

Adrenaline contributes to prenatal respiratory maturation in rat medulla-spinal cord preparation.

Adrenaline is a potent respiratory regulator. However, adrenergic contribution to the developing respiratory center has not been studied extensively. Adrenaline application on embryonic day 17 medulla-spinal cord block preparations abolished non-respiratory activity and enhanced respiratory frequency.

Dopamine desynchronizes the pace-making neuronal activity of rat respiratory rhythm generation.

In an excised Wistar rat medulla-spinal cord block preparation we previously found that dopamine slows respiratory rhythm by activation of dopamine D(4) receptors [Fujii et al., (2004)Neurosci. Res.

Development of spontaneous mouth/tongue movement and related neural activity, and their repression in fetal mice lacking glutamate decarboxylase 67.

Spontaneous body movement starts at early fetal stage, at embryonic day (E) 12-15 in mice. In the present study, the movement of the head region was studied in E13-14 mice by in utero ultrasound imaging, together with the in vitro recording of underlying neural activities in the hypoglossal nerve and the ventral root of the upper cervical cord of an isolated brainstem-spinal cord preparation. The role of gamma-aminobutyric acid (GABA) in the generation of fetal movement was assessed using mice lacking GABA-synthesizing glutamate decarboxylase 67 (GAD67).

Malfunction of respiratory-related neuronal activity in Na+, K+-ATPase alpha2 subunit-deficient mice is attributable to abnormal Cl- homeostasis in brainstem neurons.

Na+, K+-ATPase 2 subunit gene (Atp1a2) knock-out homozygous mice (Atp1a2-/-) died immediately after birth resulting from lack of breathing. The respiratory-related neuron activity in Atp1a2-/- was investigated using a brainstem-spinal cord en bloc preparation. The respiratory motoneuron activity recorded from the fourth cervical ventral root (C4) was defective in Atp1a2-/- fetuses of embryonic day 18.

In vitro visualization of respiratory neuron activity in the newborn mouse ventral medulla.

To clarify the neuronal organization of the respiratory center of the mouse, we analyzed the spatio-temporal pattern of respiratory neuron activity in the ventral medulla of a newborn mouse preparation, using optical recordings. We also demonstrated optical images of the respiratory activity of two different lines of knock-out mice (Tlx3-/-, Pbx3-/-) that exhibit respiratory failure leading to neonatal death from dysfunction of central respiratory neuron activity. In the wild type mice, the respiratory neuron activity in the para-facial region of the rostral medulla appeared prior to inspiratory activity in the more caudal ventrolateral medulla.

Purkinje cell functions in the in vitro cerebellum isolated from neonatal rats in a block with the pons and medulla.

The cerebellum dissected from neonatal rats in a block including the pons and medulla and maintained in a modified Krebs solution provides a unique preparation of brain tissue with preserved major fiber connections. Electrophysiological and optical recordings revealed that, at postnatal days 4-8 (P4-P8), Purkinje cells in the lateral portion of the cerebellum responded to the stimulation of climbing fiber afferents at the inferior olive and of parallel fibers at the posterior vermis, and that the combination of these inputs induced long-term depression. These observations and pharmacological testings indicate that certain functional features of Purkinje cells mature around P5 in the lateral portion of the cerebellum.

Dopaminergic modulation on respiratory rhythm in rat brainstem-spinal cord preparation.

Dopamine (DA) is known to regulate both higher order and autonomic brain functions. To elucidate the effects of DA on respiratory rhythm generation, isolated brainstem-spinal cord was treated with DA and each DA receptor agonist individually. DA application facilitated respiratory rhythm in pons-medulla-spinal cord preparations, but depressed it in medulla-spinal cord preparations.

Pbx3 deficiency results in central hypoventilation.

Pbx proteins comprise a family of TALE (three amino acid loop extension) class homeodomain transcription factors that are implicated in developmental gene expression through their abilities to form hetero-oligomeric DNA-binding complexes and function as transcriptional regulators in numerous cell types. We demonstrate here that one member of this family, Pbx3, is expressed at high levels predominantly in the developing central nervous system, including a region of the medulla oblongata that is implicated in the control of respiration. Pbx3-deficient mice develop to term but die within a few hours of birth from central respiratory failure due to abnormal activity of inspiratory neurons in the medulla.

Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates.

Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord.