Papers by Marjorie Parkis
Journal of Applied …, 2002
, we tested the hypothesis that ATP receptor activation also modulates phrenic MN activity. This ... more , we tested the hypothesis that ATP receptor activation also modulates phrenic MN activity. This question was examined in rhythmically active brain stem-spinal cord preparations from neonatal rats by monitoring effects of ATP on the activity of spinal C4 nerve roots and phrenic MNs. ATP produced a rapid-onset, dose-dependent, suraminand pyridoxal-phosphate-6-azophenyl-2Ј,4Ј-disulphonic acid 4-sodium-sensitive increase in C4 root tonic discharge and a 22 Ϯ 7% potentiation of inspiratory burst amplitude. This was followed by a slower, 10 Ϯ 5% reduction in burst amplitude. ATP␥S, the hydrolysis-resistant analog, evoked only the excitatory response. ATP induced inward currents (57 Ϯ 39 pA) and increased repetitive firing of phrenic MNs. These data, combined with persistence of ATP currents in TTX and immunolabeling for P2X2 receptors in Fluoro-Gold-labeled C4 MNs, implicate postsynaptic P2 receptors in the excitation. Inspiratory synaptic currents, however, were inhibited by ATP. This inhibition differed from that seen in root recordings; it did not follow an excitation, had a faster onset, and was induced by ATP␥S. Thus ATP inhibited activity through at least two mechanisms: 1) a rapid P2 receptormediated inhibition and 2) a delayed P1 receptor-mediated inhibition associated with hydrolysis of ATP to adenosine. The complex effects of ATP on phrenic MNs highlight the importance of ATP as a modulator of central motor outflows. P2 receptors; adenosine; immunohistochemistry; rat; neonate ADENOSINE-5Ј-TRIPHOSPHATE (ATP) acts on neurons through activation of two classes of purinergic receptors designated P2X and P2Y. P2X receptors, comprising seven subtypes (P2X 1-7) and several splice variants, are ionotropic, ligand-gated ion channels that mediate cation-selective inward currents involved in fast neurotransmission (25).
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 3, 2003
Synchrony and oscillations in neuronal firing play important roles in information processing in t... more Synchrony and oscillations in neuronal firing play important roles in information processing in the mammalian brain. Here, we evaluate their role in controlling neuronal output in a well defined motor behavior, breathing, using an in vitro preparation from neonatal rat that generates respiratory-related motor output. In this preparation, phrenic motoneurons (PMNs) receive endogenous rhythmic inspiratory currents with prominent oscillations in the 20-50 Hz range. We recorded these inspiratory currents in individual PMNs and used them as test inputs for the same motoneuron (MN) during the normally silent expiratory periods. The impact of the oscillations on MN output was evaluated by filtering the currents before injection. Responses to unfiltered inspiratory currents were indistinguishable from voltage changes during spontaneous inspiratory periods. More than 90% of action potentials occurred within milliseconds [-2 to +4] of the oscillation peaks. The timing of action potentials was...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1999
The movements that define behavior are controlled by motoneuron output, which depends on the exci... more The movements that define behavior are controlled by motoneuron output, which depends on the excitability of motoneurons and the synaptic inputs they receive. Modulation of motoneuron excitability takes place over many time scales. To determine whether motoneuron excitability is specifically modulated during the active versus the quiescent phase of rhythmic behavior, we compared the input-output properties of phrenic motoneurons (PMNs) during inspiratory and expiratory phases of respiration. In neonatal rat brainstem-spinal cord preparations that generate rhythmic respiratory motor outflow, we blocked excitatory inspiratory synaptic drive to PMNs and then examined their phase-dependent responses to superthreshold current pulses. Pulses during inspiration elicited fewer action potentials compared with identical pulses during expiration. This reduced excitability arose from an inspiratory-phase inhibitory input that hyperpolarized PMNs in the absence of excitatory inspiratory inputs. ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
The role of P2 receptors in controlling hypoglossal motoneuron (XII MN) output was examined (1) e... more The role of P2 receptors in controlling hypoglossal motoneuron (XII MN) output was examined (1) electrophysiologically, via application of ATP to the hypoglossal nucleus of rhythmically active mouse medullary slices and anesthetized adult rats; (2) immunohistochemically, using an antiserum against the P2X2 receptor subunit; and (3) using PCR to identify expression of P2X2 receptor subunits in micropunches of tissue taken from the XII motor nucleus. Application of ATP to the hypoglossal nucleus of mouse medullary slices and anesthetized rats produced a suramin-sensitive excitation of hypoglossal nerve activity. Additional in vitro effects included potentiation of inspiratory hypoglossal nerve output via a suramin- and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS)-sensitive mechanism, XII MN depolarization via activation of a suramin-sensitive inward current, decreased neuronal input resistance, and a slow-onset theophylline-sensitive reduction of inspiratory ...
Journal of neurophysiology, 1995
1. We used conventional intracellular recording techniques in 400-microns-thick slices from the b... more 1. We used conventional intracellular recording techniques in 400-microns-thick slices from the brain stems of juvenile rats to investigate the action of norepinephrine (NE) on subthreshold and firing properties of hypoglossal motoneurons (HMs). 2. In recordings in current-clamp mode, 50 or 100 microM NE elicited a reversible depolarization accompanied by an increase in input resistance (RN) in all HMs tested (n = 74). In recordings in single-electrode voltage-clamp mode, NE induced a reversible inward current (INE) accompanied by a reduction in input conductance. The average reversal potential for INE was -104 mV. The NE responses could be elicited in a Ca(2+)-free solution containing tetrodotoxin, indicating that they were postsynaptic. 3. The NE response could be blocked by the alpha-adrenoceptor antagonist prazosin, but not by the beta-adrenoceptor antagonist propranolol, and could be mimicked by the alpha 1-adrenoceptor agonist phenylephrine but not by the alpha 2-adrenoceptor ...
Respiration Physiology, 1997
Proper function of hypoglossal motoneurons (XII MNs) innervating tongue muscles is critical for r... more Proper function of hypoglossal motoneurons (XII MNs) innervating tongue muscles is critical for respiratory control of the airway. Morphological and electrophysiological properties of XII MNs change during postnatal development, as do modulatory systems. Despite these changes, the system producing respiratory movements must remain fully functional throughout life. Modulatory systems have therefore received considerable attention since coordination of their development with a developing neuromuscular system may be critical for maintenance of continuous, efficient breathing. Developmental modulation of XII inspiratory activity by three transmitter systems is examined. Thyrotropin-releasing hormone (TRH) mediates an increase in MN input resistance (RN) in juvenile but not neonate MNs, and this likely underlies the developmental increase in TRH potentiation of inspiratory activity. Norepinephrine (NE) potentiation of inspiratory activity, which in the neonate is produced in part by an alpha 1-mediated increase in RN, also increases postnatally. Effects of purinergic transmission on XII inspiratory activity remain constant during the first 2 weeks of postnatal development. Adenosine-triphosphate (ATP) produces tonic excitation and inspiratory potentiation that likely result from activation of postsynaptic P2 receptors. A secondary inhibitory effect likely results from hydrolysis of ATP to adenosine and activation of presynaptic A1 adenosine receptors. The functional relevance of these postnatal changes is discussed.
Neuron, 2004
Pacemaker neurons have been described in most neural networks. However, whether such neurons are ... more Pacemaker neurons have been described in most neural networks. However, whether such neurons are essential for generating an activity pattern in a given preparation remains mostly unknown. Here, we show that in the mammalian respiratory network two types of pacemaker neurons exist. Differential blockade of these neurons indicates that their relative contribution to respiratory rhythm generation changes during the transition from normoxia to hypoxia. During hypoxia, blockade of neurons with sodium-dependent bursting properties abolishes respiratory rhythm generation, while in normoxia respiratory rhythm generation only ceases upon pharmacological blockade of neurons with heterogeneous bursting properties. We propose that respiratory rhythm generation in normoxia depends on a heterogeneous population of pacemaker neurons, while during hypoxia the respiratory rhythm is driven by only one type of pacemaker.
Journal of Neuroscience Methods, 2000
Neuronal input-output functions are traditionally studied using rectangular or ramp waveforms of ... more Neuronal input-output functions are traditionally studied using rectangular or ramp waveforms of injected current. These waveforms are easy to produce and responses to them easy to quantify; thus they have been central to our understanding of the roles that membrane properties play in controlling repetitive firing. However, since smooth rectangular step and ramp waveforms lack the dynamic features of endogenous synaptic input, their use has the potential to underemphasize the importance of input patterns in controlling physiological patterns of neuronal output. To activate neurons with current waveforms that replicate natural synaptic input, we developed a method for acquiring, digitally manipulating and reinjecting endogenous synaptic currents. We demonstrate, by applying this technique to phrenic motoneurons (PMNs) in rhythmically-active in vitro preparations from neonatal rats, that stimulation of neurons with endogenous current waveforms produces responses that mimic those produced by spontaneous synaptic inputs. Acquired waveforms can be reinjected repeatedly to produce consistent responses, and can also be amplified or filtered prior to reinjection to yield a range of information including standard descriptors of firing behavior such as frequency/current plots. This technique provides a valuable tool for analysing characteristics of the synaptic waveform important in generating neuronal output and how synaptic factors interact with membrane properties to control repetitive firing.
Brain Research, 1998
The ontogeny of the noradrenergic receptor subtypes modulating hypoglossal (XII) nerve inspirator... more The ontogeny of the noradrenergic receptor subtypes modulating hypoglossal (XII) nerve inspiratory output was characterized. Noradrenergic agents were locally applied over the XII nucleus of rhythmically active medullary slice preparations isolated from mice between zero and 13 days of age (P0-P13) and the effects on XII inspiratory burst amplitude quantified. The alpha1 receptor agonist phenylephrine (PE, 0.1-10 microM) produced a dose-dependent, prazosin-sensitive (0.1-10 microM) increase in XII nerve inspiratory burst amplitude. The magnitude of this potentiation increased steadily from a maximum of 15+/-8% in P0 mice to 134+/-4% in P12-P13 mice. The beta receptor agonist isoproterenol (0.01-1.0 mM) produced a prazosin-insensitive, propranolol-sensitive potentiation of XII nerve burst amplitude. The isoproterenol-mediated potentiation increased with development from 27+/-5% in P0-P1 slices, to 37+/-3% in P3 slices and 45+/-4% in P9-P10 slices. The alpha2 receptor agonist clonidine (1 mM) reduced XII nerve inspiratory burst amplitude in P0-P3 slices by 29+/-5%, but had no effect on output from P12-P13 slices. An alpha2 receptor-mediated inhibition of inspiratory activity in neonates (P0-P3) was further supported by a 19+/-3% reduction in XII nerve burst amplitude when norepinephrine (NE, 100 microM) was applied in the presence of prazosin (10 microM) and propranolol (100 microM). Results indicate that developmental increases in potentiating alpha1 and, to a lesser extent, beta receptor mechanisms combine with a developmentally decreasing inhibitory mechanism, most likely mediated by alpha2 receptors, to determine the ontogenetic time course by which NE modulates XII MN inspiratory activity.
1. Martin-Caraballo M, Greer JJ: Electrophysiological properties of rat phrenic motoneurons durin... more 1. Martin-Caraballo M, Greer JJ: Electrophysiological properties of rat phrenic motoneurons during the perinatal development. J Neurophysiol 1999, 81:1365-1378 2. Greer JJ, Allan DW, Martin-Caraballo M, Lemke RP: Invited Review: An overview of phrenic nerve and diaphragm muscle development in the perinatal rat. J Appl Physiol 1999, 86:779-786 3. Martin-Caraballo M, Campagnaro PA, Gao Y, Greer JJ: Contractile properties of the rat diaphragm during the perinatal period. J Appl Physiol 2000, 88:573-580 4. Martin-Caraballo M, Greer JJ: Development of potassium conductances in perinatal rat phrenic motoneurons. J Neurophysiol 2000, 83:3497-3508 5. Martin-Caraballo M, Greer JJ: Voltage-sensitive calcium currents and their role in regulating phrenic motoneuron electrical excitability during the perinatal period. J Neurobiol 2001, 46:231-248 Acknowledgements: Funded by CIHR, AHFMR and Alberta Lung Association.
Respiratory Physiology & Neurobiology, 2002
Inspiratory activities, whether recorded from medullary neurons, motoneurons or motor nerves, fea... more Inspiratory activities, whether recorded from medullary neurons, motoneurons or motor nerves, feature prominent oscillations in high (50-120 Hz) and medium (15-50 Hz) frequency ranges. These oscillations have been extensively characterized and are considered signatures of respiratory network activity. Their functional significance, however, if any, remains unknown. Here we review the literature describing the nature and origin of these oscillations as well as their modulation during development and by mechanoreceptive and chemoreceptive feedback, respiratory-and non-respiratory-related behaviors, temperature and anesthesia. We then consider the potential significance of these oscillations for respiratory network function by drawing on analyses of distributed motor and sensory networks of the cortex where current interest in oscillatory activity, and the synchronization of neural discharge that can result, is based on the increased efficacy with which synchronous inputs influence neuronal output, and the role that synchronous activity may play in information coding. We speculate that synchronized oscillations at the network level help coordinate activity in distributed rhythm and pattern generating systems and at the muscle level enhance force development. Data most strongly support that oscillatory synaptic inputs play an important role in controlling timing and pattern of action potential output.
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Papers by Marjorie Parkis