Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: involvement of Src tyrosine kinase.

The discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is highly expressed in breast carcinoma cells. Upon binding to collagen, DDR1 undergoes autophosphorylation followed by limited proteolysis to generate a tyrosine phosphorylated C-terminal fragment (CTF). Although it was postulated that this fragment is formed as a result of shedding of the N-terminal ectodomain, collagen-dependent release of the DDR1 extracellular domain has not been demonstrated.

Adhesion-dependent redistribution of MAP kinase and MEK promotes muscarinic receptor-mediated signaling to the nucleus.

The mitogen-activated protein kinases (MAPKs) are activated by extracellular signals, and translocate to the nucleus where they modulate transcription. Integrin-mediated cell adhesion to extracellular matrix (ECM) proteins is required for efficient transmission of MAPK-based signals initiated by growth factors. However, the modulation of G protein-coupled receptor (GPCR) signaling by adhesion is less well understood.

DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals.

DNA methyltransferase I (Dnmt1), the maintenance enzyme for DNA cytosine methylation, is expressed at high levels in the CNS during embryogenesis and after birth. Because embryos deficient for Dnmt1 die at gastrulation, the role of Dnmt1 in the development and function of the nervous system could not be studied by using this mutation. We therefore used the cre/loxP system to produce conditional mutants that lack Dnmt1 in neuroblasts of embryonic day 12 embryos or in postmitotic neurons of the postnatal animal.

Plasticity of cardiorespiratory neural processing: classification and computational functions.

Neural plasticity, or malleability of neuronal structure and function, is an important attribute of the mammalian forebrain and is generally thought to be a kernel of biological intelligence. In this review, we examine some reported manifestations of neural plasticity in the cardiorespiratory system and classify them into four functional categories, integral; differential; memory; and statistical-type plasticity. At the cellular and systems level the myriad forms of cardiorespiratory plasticity display emergent and self-organization properties, use- and disuse-dependent and pairing-specific properties, short-term and long-term potentiation or depression, as well as redundancy in series or parallel structures, convergent pathways or backup and fail-safe surrogate pathways.

High-pass filtering of carotid-vagal influences on expiration in rat: role of N-methyl-D-aspartate receptors.

Repetitive electrical stimulation of the carotid sinus nerve or vagus nerve in rats elicited abrupt reflex shortening or prolongation, respectively, of the inter-burst interval of phrenic nerve activity followed by exponential decay from the initial response. Removal of the stimuli resulted in transient post-stimulus rebound excitation or inhibition that mirrored the corresponding stimulus-evoked responses. The biphasic responses to these complementary inputs approximate the on- and off-transients of full-wave differentiators or high-pass filters.

Habituation and desensitization of the Hering-Breuer reflex in rat.

1. Many processes in mammalian and invertebrate central nervous systems exhibit habituation and/or sensitization of their responses to repetitive stimuli. Here, we studied the adaptive behaviours of the respiratory pattern generator in rat on repetitive vagal-afferent stimulation and compared these behaviours obtained in vivo with the reported effects of such stimuli on synaptic transmission in the corresponding signal pathway in vitro.

Short-term potentiation of carotid chemoreflex: an NMDAR-dependent neural integrator.

Repetitive stimulation of the carotid sinus nerve (CSN) elicits a short-term potentiation (STP) of the reflex response in respiratory motor output in mammals. The input-output transformation approximates a leaky integrator with a time constant of several seconds. Here, we showed that STP induced by CSN stimulation in rats was manifested in the reflex response in the amplitude of rhythmic phrenic nerve activity as well as its duration.

Recovery of retching after lesions involving the nucleus of the solitary tract.

The nucleus of the solitary tract (NTS) in the caudal brainstem receives various inputs that trigger vomiting. Chemical (kainic acid) NTS lesions in decerebrate, paralyzed cats temporarily suppressed fictive vomiting induced by different emetics. Subsequently, retching but not expulsion, resumed in 2-3.

Vestibular effects on upper airway musculature.

The vestibular system produces a variety of compensatory responses to accelerations of the head, which include reflex responses recorded from respiratory muscle nerves of the thorax and abdomen. In order to better understand the functional significance of vestibulo-respiratory reflexes, we investigated the extent to which such responses are also present on muscle nerves of the upper airway. Experiments were conducted on adult cats that were decerebrated, paralyzed, and artificially ventilated.

Role of ventral respiratory group bulbospinal expiratory neurons in vestibular-respiratory reflexes.

1. Activation of the vestibular system produces reflex modulation of expiratory muscle activity. The purpose of the present study was to investigate the possible role of bulbospinal expiratory (E) neurons located in the caudal ventral respiratory group (VRG) in mediating vestibulo-respiratory reflexes.

Multifunctional ventral respiratory group: bulbospinal expiratory neurons play a role in pudendal discharge during vomiting.

Pudendal motoneurons are activated in phasic bursts during the retching and expulsion phases of vomiting. The resulting contraction of the anal and urethral sphincters serves to maintain continence during the large increase in abdominal pressure that occurs during vomiting. We evaluated the contribution of bulbospinal expiratory neurons located in the portion of the ventral respiratory group (VRG) caudal to the obex (nucleus retroambigualis) to the control of pudendal motoneurons during fictive vomiting in decerebrate, paralyzed cats.

Descending pathways necessary for vestibular influences on sympathetic and inspiratory outflow.

The objective of this study was to determine which brain stem regions that have projections to sympathetic preganglionic neurons or phrenic motoneurons ae necessary for vestibulosympathetic or vestibulorespiratory responses in decerebrate cats. Bilateral kainic acid injections into the rostral ventrolateral medulla abolished splanchnic nerve responses to electrical stimulation of the vestibular nerve, suggesting that this region is critical for the production of vestibulosympathetic responses. In contrast, injections into the caudal medullary raphe nuclei had no apparent effect on the responses.

Ventral respiratory group bulbospinal inspiratory neurons participate in vestibular-respiratory reflexes.

1. The vestibular system responds to accelerations of the head and produces reflex responses that serve a variety of compensatory functions. The neuronal circuitry that mediates vestibulo-respiratory reflexes is largely unknown.

[The compensatory plasticity of the brain when it is damaged].

A new test for determination of the degree of the compensatory processes after brain damage was proposed in experiments in the cats with one-sided transection of the hemisphere and children with one-sided cerebral palsy. The process of habituation of the skin galvanic reaction was used for this aim.

[Functional reorganization in the system of corticotectal connections after unilateral deafferentation of the cortex].

The responses of the cat's collicular neurons to direct stimulation (DCR) of contralateral neocortex were studied in various periods after unilateral dissection of cortico-subcortical connections. The data obtained suggest that, in intact cat's brain, during early hours of postoperative period, and within 1-2 years after the operation, functional specifics of contralateral motor and sensory projections to superior colliculus played a major part in determining basic features of compensatory shifts of the impulse activity of collicular neurons.