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Nino Ramirez, PhD

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Nino Ramirez, PhD

Children's Title: Director, Center for Integrative Brain Research

Academic Title: Principal Investigator

Research Center: Center for Integrative Brain Research

Making a Difference

  • A Thriving Biomedical Community

    Partnering with UW and the Hutchinson Center for world-class science.... cont.

  • Families Fuel Discovery

    Many rare and devastating diseases lack effective treatments or cures. The faith, funds and passion of families of our patients jump-start the search for answers that will help seriously ill children lead healthier lives.... cont.

Overview

Research Description

Educational History:
University of Regensburg, FRG; M.Sc, 1983, Biology
University of Regensburg, FRG; Ph.D., 1986, Biology
University of Alberta, Canada; Post Doc, 1986-1991, Physiology
University of Regensburg, FRG; Habilitation, 1994, Zoology

Research Description:
Our studies focus on understanding the neuronal basis of a variety of brain functions to find novel ways to treat and cure neurological disorders in children, including epilepsy, Rett syndrome, brain tumors, and sudden infant death syndrome (SIDS).

With the introduction of molecular approaches into the field of neuroscience an unexpected variety of receptor and ion channel subtypes have been discovered that are developmentally regulated within the central nervous system. The relevance of these findings for the function of neuronal networks is still unclear. In a close combination of studies at the cellular and systems level our laboratory examines how diversity at the cellular level may lead to ontogenetic changes at the network level.

Over the past decade we have analyzed cellular mechanisms in neuronal networks that generate rhythmic motor activity in invertebrates and vertebrates. Our current work focuses on the analysis of the in vitro respiratory network in mice. For this purpose we isolate acutely the respiratory network in a transverse plane of the mouse medulla. This brainstem slice preparation contains the essential medullary structures involved in cardio-respiratory control and even after the in vitro isolation generates rhythmic activity in rats and mice of all developmental stages (up to an age of 25 postnatal days). This approach permits a direct comparison of the neuronal mechanisms of rhythmogenesis in newborn and more mature mammals. Our experiments indicate e.g. that the hypoxic response, fast chloride mediated inhibitory synaptic transmission, calcium channels and modulatory processes change postnatally within the respiratory network.

In order to analyze the cellular mechanisms in rhythm generating neural networks we employ the currently available electrophysiological and immunohistochemical techniques. The great advantage of the brainstem slice preparation is that single neurons can be visualized that are embedded in a functional neuronal network using infrared-Normarski optics in conjunction with upright microscopes. Thus, voltage-gated and synaptic whole cell currents, properties of single channels as well as second messenger pathways can be investigated in a functional context to characterize changes in postnatal development of the respiratory network. Our laboratory is particularly interested in understanding developmental alterations of cellular properties involved in the response of the respiratory network to hypoxia. This response elicits a cascade of molecular events which are regulated by endogenously released neuromodulators such as substance P and endorphins and which result in a reconfiguration of the respiratory neuronal network.

In the future this slice preparation will enable us to further obtain systems and cellular data from functionally identified respiratory neurons. In combination with cell culture and modern molecular techniques (e.g. expression of channel subtypes obtained from respiratory neurons in oocytes) we expect to gain new insights into principle mechanisms of respiratory rhythm generation and the hypoxic response in mammals. Due to the importance of the respiratory system for the survival of any mammal, progress in this field will not only have important scientific, but also clinical implications (e.g. understanding the underlying causes of sleep apnea, periodic breathing, Pickwick syndrome and sudden infant death syndrome "SIDS").

Research Focus Area

Neuroscience / Neurodevelopment

Publications

Network Reconfiguration and Neuronal Plasticity in Rhythm-Generating Networks.
Integrative and comparative biology , 2011 Aug 19
Network Reconfiguration and Neuronal Plasticity in Rhythm-Generating Networks.
Integrative and comparative biology , 2011 Aug 19
Hydrogen peroxide differentially affects activity in the preBotzinger Complex and hippocampus.
Journal of neurophysiology , 2011 Aug 17
Hydrogen peroxide differentially affects activity in the preBotzinger Complex and hippocampus.
Journal of neurophysiology , 2011 Aug 17
Activation of alpha-2 noradrenergic receptors is critical for the generation of fictive eupnea and fictive gasping inspiratory activities in mammals in vitro.
The European journal of neuroscience , 2011 Jun: 2228-37
Activation of alpha-2 noradrenergic receptors is critical for the generation of fictive eupnea and fictive gasping inspiratory activities in mammals in vitro.
The European journal of neuroscience , 2011 Jun: 2228-37
Calcium-activated non-selective cation currents are involved in generation of tonic and bursting activity in dopamine neurons of the substantia nigra pars compacta.
The Journal of physiology , 2011 May 15: 2497-514
Slow intrinsic oscillations in thick neocortical slices of hypoxia tolerant deep diving seals.
Neuroscience , 2011 Mar 17: 35-42
Slow intrinsic oscillations in thick neocortical slices of hypoxia tolerant deep diving seals.
Neuroscience , 2011 Mar 17: 35-42
Inner ear insult suppresses the respiratory response to carbon dioxide.
Neuroscience , 2011 Feb 23: 262-72
Inner ear insult suppresses the respiratory response to carbon dioxide.
Neuroscience , 2011 Feb 23: 262-72
Graded reductions in oxygenation evoke graded reconfiguration of the isolated respiratory network.
Journal of neurophysiology , 2011 Feb: 625-39
Graded reductions in oxygenation evoke graded reconfiguration of the isolated respiratory network.
Journal of neurophysiology , 2011 Feb: 625-39
The human pre-Bötzinger complex identified.
Brain : a journal of neurology , 2011 Jan: 8-10
Chapter 3--networks within networks: the neuronal control of breathing.
Progress in brain research , 2011: 31-50
The human pre-Bötzinger complex identified.
Brain : a journal of neurology , 2011 Jan: 8-10
Chapter 3--networks within networks: the neuronal control of breathing.
Progress in brain research , 2011: 31-50
Neuronal bursting properties in focal and parafocal regions in pediatric neocortical epilepsy stratified by histology.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society , 2010 Dec: 387-97
N-methyl-D-aspartate-induced oscillatory properties in neocortical pyramidal neurons from patients with epilepsy.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society , 2010 Dec: 398-405
Neuronal bursting properties in focal and parafocal regions in pediatric neocortical epilepsy stratified by histology.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society , 2010 Dec: 387-97
Prostaglandin E2-induced synaptic plasticity in neocortical networks of organotypic slice cultures.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2010 Sep 1: 11678-87
Prostaglandin E2-induced synaptic plasticity in neocortical networks of organotypic slice cultures.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2010 Sep 1: 11678-87
State-dependent interactions between excitatory neuromodulators in the neuronal control of breathing.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2010 Jun 16: 8251-62
State-dependent interactions between excitatory neuromodulators in the neuronal control of breathing.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2010 Jun 16: 8251-62
Neuron-specific cholinergic modulation of a forebrain song control nucleus.
Journal of neurophysiology , 2010 Feb: 733-45
Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in the respiratory network after birth.
Respiratory physiology & neurobiology , 2009 Aug 31: 101-8
Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in the respiratory network after birth.
Respiratory physiology & neurobiology , 2009 Aug 31: 101-8
Neuromodulation and the orchestration of the respiratory rhythm.
Respiratory physiology & neurobiology , 2008 Dec 10: 96-104
Neuromodulation and the orchestration of the respiratory rhythm.
Respiratory physiology & neurobiology , 2008 Dec 10: 96-104
Remarkable neuronal hypoxia tolerance in the deep-diving adult hooded seal (Cystophora cristata).
Neuroscience letters , 2008 Dec 3: 147-50
Remarkable neuronal hypoxia tolerance in the deep-diving adult hooded seal (Cystophora cristata).
Neuroscience letters , 2008 Dec 3: 147-50
Autonomic dysregulation in young girls with Rett Syndrome during nighttime in-home recordings.
Pediatric pulmonology , 2008 Nov: 1045-60
Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation.
Neuron , 2008 Aug 28: 568-80
Differential modulation of neural network and pacemaker activity underlying eupnea and sigh-breathing activities.
Journal of neurophysiology , 2008 May: 2114-25
Differential modulation of neural network and pacemaker activity underlying eupnea and sigh-breathing activities.
Journal of neurophysiology , 2008 May: 2114-25
Point: Medullary pacemaker neurons are essential for both eupnea and gasping in mammals.
Journal of applied physiology (Bethesda, Md. : 1985) , 2007 Aug: 717-8; discussion 722
Activity deprivation leads to seizures in hippocampal slice cultures: is epilepsy the consequence of homeostatic plasticity?
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society , 2007 Apr: 154-64
Hypoxia tolerance in mammals and birds: from the wilderness to the clinic.
Annual review of physiology , 2007: 113-43
Macroglial and retinal changes in hypercholesterolemic rabbits after normalization of cholesterol levels.
Experimental eye research , 2006 Dec: 1423-38
Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro.
Journal of neurophysiology , 2006 Nov: 2564-77
Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome.
Pediatric research , 2006 Oct: 443-9
Norepinephrine differentially modulates different types of respiratory pacemaker and nonpacemaker neurons.
Journal of neurophysiology , 2006 Apr: 2070-82
Gasping activity in vitro: a rhythm dependent on 5-HT2A receptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2006 Mar 8: 2623-34
Pattern-specific synaptic mechanisms in a multifunctional network. II. Intrinsic modulation by metabotropic glutamate receptors.
Journal of neurophysiology , 2006 Mar: 1334-44
Pattern-specific synaptic mechanisms in a multifunctional network. I. Effects of alterations in synapse strength.
Journal of neurophysiology , 2006 Mar: 1323-33
Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2005 Dec 14: 11521-30
Hypoxia-induced changes in neuronal network properties.
Molecular neurobiology , 2005 Dec: 251-83
Determinants of inspiratory activity.
Respiratory physiology & neurobiology , 2005 Jul 28: 145-57
Pacemaker neurons and neuronal networks: an integrative view.
Current opinion in neurobiology , 2004 Dec: 665-74
Hyperthermia modulates respiratory pacemaker bursting properties.
Journal of neurophysiology , 2004 Nov: 2844-52
Background sodium current stabilizes bursting in respiratory pacemaker neurons.
Journal of neurobiology , 2004 Sep 15: 481-9
Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2004 Aug 25: 7549-56
Differential contribution of pacemaker properties to the generation of respiratory rhythms during normoxia and hypoxia.
Neuron , 2004 Jul 8: 105-17
Synchrony levels during evoked seizure-like bursts in mouse neocortical slices.
Journal of neurophysiology , 2003 Sep: 1571-80
Response of the respiratory network of mice to hyperthermia.
Journal of neurophysiology , 2003 Jun: 2975-83
Stabilization of bursting in respiratory pacemaker neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2003 Apr 15: 3538-46
Endogenous activation of serotonin-2A receptors is required for respiratory rhythm generation in vitro.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2002 Dec 15: 11055-64
Heart rate changes in response to mild mechanical irritation of the high cervical spinal cord region in infants.
Forensic science international , 2002 Aug 28: 168-76
Long-term deprivation of substance P in PPT-A mutant mice alters the anoxic response of the isolated respiratory network.
Journal of neurophysiology , 2002 Jul: 206-13
Respiratory rhythm generation: converging concepts from in vitro and in vivo approaches?
Respiratory physiology & neurobiology , 2002 Jul: 43-56
Special issue: 'Neural Control of Breathing'.
Respiratory physiology & neurobiology , 2002 Jul: 1-3
Long-term modulation of respiratory network activity following anoxia in vitro.
Journal of neurophysiology , 2002 Jun: 2964-71
Identification of two types of inspiratory pacemaker neurons in the isolated respiratory neural network of mice.
Journal of neurophysiology , 2001 Jul: 104-12
Role of inspiratory pacemaker neurons in mediating the hypoxic response of the respiratory network in vitro.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2000 Aug 1: 5858-66
Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps [see comment].
Nature neuroscience , 2000 Jun: 600-7
The role of the hyperpolarization-activated current in modulating rhythmic activity in the isolated respiratory network of mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2000 Apr 15: 2994-3005
Differential responses of respiratory nuclei to anoxia in rhythmic brain stem slices of mice.
Journal of neurophysiology , 1999 Nov: 2163-70
Reconfiguration of the respiratory network at the onset of locust flight.
Journal of neurophysiology , 1998 Dec: 3137-47
Respiratory rhythm generation in mammals: synaptic and membrane properties.
Respiration physiology , 1997 Nov: 71-85
Developmental changes in the hypoxic response of the hypoglossus respiratory motor output in vitro.
Journal of neurophysiology , 1997 Jul: 383-92
Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice.
The Journal of physiology , 1996 Mar 15: 799-812
Mechanisms of respiratory rhythm generation change profoundly during early life in mice and rats.
Neuroscience letters , 1994 Mar 28: 167-70

Primary Office

Seattle Children's Research Institute
JMB -10 - Integrative Brain Research
1900 - 9th Ave
Seattle, WA 98101
206-884-1025

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