Biomedical subjects

G D Funk

Publications and source records attributed to G D Funk.

At least 19 recordsLinked to original sources

PubMed2000

Calcium binding proteins in motoneurons at low and high risk for degeneration in ALS.

Recent reports challenge the hypothesis that expression of calcium binding proteins contributes to the greater resistance of some motoneurons to degeneration in amyotrophic lateral sclerosis (ALS). We therefore re-examined, using immunohistochemistry, the expression of calbindin, calretinin and parvalbumin in vulnerable (hypoglossal, XII; and cervical spinal) and resistant (oculomotor, III) motoneurons of adult rats. Calbindin immunoreactivity was lacking in motor nuclei but strong in the dorsal horn. Calretinin was expressed in spinal, but not III or XII, motoneurons. Parvalbumin immunoreactivity, tested with a polyclonal antibody, was intense in spinal and III, but not XII, motoneurons; however, no staining in the ventral horn was observed with a monoclonal antibody. Differential expression of calretinin and parvalbumin within vulnerable motoneurons suggests that immunoreactivity for these proteins is not a reliable marker for resistance to degeneration in ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2000

A method for activating neurons using endogenous synaptic waveforms.

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.

Action Potentials↗

PubMed2000

Development of the ventilatory response to hypoxia in Swiss CD-1 mice.

We examined developmental changes in breathing pattern and the ventilatory response to hypoxia (7.4% O(2)) in unanesthetized Swiss CD-1 mice ranging in age from postnatal day 0 to 42 (P(0)-P(42)) using head-out plethysmography. The breathing pattern of P(0) mice was unstable. Apneas were frequent at P(0) (occupying 29 +/- 6% of total time) but rare by P(3) (5 +/- 2% of total time). Tidal volume increased in proportion to body mass ( approximately 10-13 ml/kg), but increases in respiratory frequency (f) (55 +/- 7, 130 +/- 13, and 207 +/- 20 cycles/min for P(0), P(3), and P(42), respectively) were responsible for developmental increases in minute ventilation (690 +/- 90, 1,530 +/- 250, and 2,170 +/- 430 ml. min(-1). kg(-1) for P(0), P(3), and P(42), respectively). Between P(0) and P(3), increases in f were mediated by reductions in apnea and inspiratory and expiratory times; beyond P(3), increases were due to reductions in expiratory time. Mice of all ages showed a biphasic hypoxic ventilatory response, which differed in two respects from the response typical of most mammals. First, the initial hyperpnea, which was greatest in mature animals, decreased developmentally from a maximum, relative to control, of 2.58 +/- 0.29 in P(0) mice to 1. 32 +/- 0.09 in P(42) mice. Second, whereas ventilation typically falls to or below control in most neonatal mammals, ventilation remained elevated relative to control throughout the hypoxic exposure in P(0) (1.73 +/- 0.31), P(3) (1.64 +/- 0.29), and P(9) (1. 34 +/- 0.17) mice but not in P(19) or P(42) mice.

Aging↗

PubMed2000

Synaptic control of motoneuronal excitability.

Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K(+) current, cationic inward current, hyperpolarization-activated inward current, Ca(2+) channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior.

Action Potentials↗

PubMed1999

Concurrent inhibition and excitation of phrenic motoneurons during inspiration: phase-specific control of excitability.

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. Local application of bicuculline blocked this inhibition as well as the difference between inspiratory and expiratory firing. Correspondingly, bicuculline locally applied to the midcervical spinal cord enhanced fourth cervical nerve (C4) inspiratory burst amplitude. Strychnine had no effect on C4 output. Nicotinic receptor antagonists neither potentiated C4 output nor blocked its potentiation by bicuculline, further indicating that the inhibition is not from recurrent inhibitory pathways. We conclude that it is bulbospinal in origin. These data demonstrate that rapid changes in motoneuron excitability occur during behavior and suggest that integration of overlapping, opposing synaptic inputs to motoneurons is important in controlling motor outflow. Modulation of phasic inhibition may represent a means for regulating the transfer function of PMNs to suit behavioral demands.

Animals↗

PubMed1998

Developmental modulation of mouse hypoglossal nerve inspiratory output in vitro by noradrenergic receptor agonists.

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.

Adrenergic Agonists↗

PubMed1997

P2 receptor excitation of rodent hypoglossal motoneuron activity in vitro and in vivo: a molecular physiological analysis.

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 output likely resulting from hydrolysis of extracellular ATP to adenosine and activation of P1 receptors. Immunohistochemically, P2X2 receptors were detected in inspiratory XII MNs that were labeled with Lucifer yellow. These data, combined with identification of mRNA for three P2X2 receptor subunit isoforms within the hypoglossal nucleus (two of which have not been localized previously in brain) and the previous demonstration that P2X receptors are ubiquitously expressed in cranial and spinal motoneuron pools, support not only a role of P2 receptors in modulating inspiratory hypoglossal activity but a general role of P2 receptors in modulating motor outflow from the CNS.

Adenosine↗

PubMed1997

Developmental modulation of glutamatergic inspiratory drive to hypoglossal motoneurons.

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.

Adenosine Triphosphate↗

PubMed1997

Functional respiratory rhythm generating networks in neonatal mice lacking NMDAR1 gene.

N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission is implicated in activity-dependent developmental reorganization in mammalian brain, including sensory systems and spinal motoneuron circuits. During normal development, synaptic interactions important in activity-dependent modification of neuronal circuits may be driven spontaneously (Shatz 1990b). The respiratory system exhibits substantial spontaneous activity in utero; this activity may be critical in assuring essential and appropriate breathing movements from birth. We tested the hypothesis that NMDA receptors are necessary for prenatal development of central neural circuits underlying respiratory rhythm generation by comparing the responsiveness of control mice and mutant mice lacking the NMDA receptor R1 subunit (NMDAR1) gene to glutamate receptor agonists and antagonists and comparing endogenous respiratory-related oscillations generated in vitro by brain stem-spinal cord and medullary slice preparations from control and mutant mice. In control mice, local application of NMDA and the non-NMDA receptor agonist, (R,S)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide (AMPA), over the pre-Bötzinger Complex, the C4 cervical motor neuron pool, and the hypoglossal motor nucleus produced profound increases in inspiratory frequency, tonic discharge on C4 ventral nerve roots, and inward currents in inspiratory hypoglossal motoneurons, respectively. Responses of mutant mice to AMPA were similar. However, mutant mice were completely unresponsive to NMDA applications. Preparations from mutant mice generated a respiratory rhythm virtually identical to control. Results demonstrate that NMDA receptors are not essential for respiratory rhythm generation or drive transmission in the neonate. More importantly, they suggest that NMDA receptors are not obligatory for the prenatal development of circuits producing respiratory rhythm.

Animals↗

PubMed1996

Rhythmical oral-motor activity recorded in an in vitro brainstem preparation.

The present study employed the neonatal rat isolated brainstem preparation to determine whether oral-motor rhythmical activity, a substrate for the complex behaviors of suckling and chewing, could be elicited in vitro by path application of excitatory amino acids (EAAs). Bath application of EAA agonists (kainate [KA], [+/-]-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA], N-methyl-D, L-aspartate [NMA]), in conjunction with the gamma-aminobutyric acid antagonist bicuculline, either failed to induce rhythmic activity (n = 17 preparations) or induced a low-amplitude, low-frequency burst discharge (< 1 Hz, n = 10 preparations) from the motor branches of the trigeminal nerves when the brainstem was contiguous from the spinomedullary junction to the superior colliculus. Burst activity was in most cases bilaterally synchronous. However, when a discrete coronal transection was made at the level of the facial colliculus, between the trigeminal and facial motor nuclei, the rhythmic bursts produced by the resultant 3- to 5-mm block of tissue following bath application of EAA agonists increased in amplitude and frequency (4-8 Hz, n = 35). Application of 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, blocked the rhythm induced by non-NMDA receptor agonist (n = 4) but was less effective in suppressing NMA-induced rhythmicity. In contrast, D, L-2-amino-5-phosphonovaleric acid (APV) blocked by both NMA-induced (n = 5) and, in most cases, KA-induced (n = 5) rhythmicity, suggesting an essential role for NMA receptors in production of EAA-induced rhythmical oral-motor activity in the neonatal rat. The present data demonstrate that a narrow, bilaterally distributed region of brainstem surrounding the trigeminal motor nucleus contains sufficient neuronal circuitry for the production of oral-motor rhythmogenesis.

Animals↗

PubMed1995

Generation of respiratory rhythm and pattern in mammals: insights from developmental studies.

Our understanding of the cellular, synaptic and network mechanisms underlying respiratory rhythm generation in mammals is progressing rapidly as researchers focus on a site hypothesized as the source of rhythm generation, the preBötzinger complex, in the rostral ventrolateral medulla. Furthermore, ontogenetic and modulatory factors affecting respiratory neuronal circuits are receiving considerable attention, as postnatal development of motor systems becomes increasingly apparent.

Animals↗

PubMed1995

Modulation of neural network activity in vitro by cyclothiazide, a drug that blocks desensitization of AMPA receptors.

To determine whether AMPA receptor channel desensitization has a physiological role in shaping network activity by modulating signal transmission through excitatory circuits, we examined the effects of cyclothiazide (CYT), the most potent known blocker of AMPA receptor desensitization, on the behavior of an endogenously active neural system in vitro, the brainstem network generating rhythmic respiratory oscillations in neonatal rat medullary slices. Bath application of 100 microM CYT significantly increased the frequency of endogenously generated rhythm and increased the amplitude of the circuit output [i.e., discharge of hypoglossal (XII) respiratory motoneurons]. Local application of CYT within the XII motor nucleus produced a concentration-dependent increase (up to 35%) in amplitude of the motoneuron population discharge as well as an increase in the peak current (23%) and total charge transfer of the rhythmic inspiratory synaptic drive (33%) to individual XII motoneurons. CYT also acted postsynaptically to increase the amplitude of spontaneous EPSCs in motoneurons. In addition, CYT produced a profound, long-term augmentation of network frequency and motor output that may be secondary to block of desensitization. These results suggest that AMPA receptor desensitization has functionally significant effects on the temporal behavior and output of the rhythmic, respiratory neural network, and, by extrapolation, on other integrative actions of the mammalian CNS.

Animals↗

PubMed1994

Development of thyrotropin-releasing hormone and norepinephrine potentiation of inspiratory-related hypoglossal motoneuron discharge in neonatal and juvenile mice in vitro.

1. The ontogeny of thyrotropin-releasing hormone (TRH) and norepinephrine (NE) potentiation of inspiratory-related hypoglossal (XII) motor nerve discharge was studied in medullary slices from P0-3, P7, and P11-14 mice that retain functional networks for respiration. 2. TRH, applied locally to the XII motor nucleus, had no effect on XII inspiratory burst amplitude in slices from P0-3 mice. By P7 there was significant potentiation of burst amplitude that increased more than three-fold by P11-14. NE applied to the XII nucleus produced significant potentiation in all age groups. Potentiation increased developmentally with the largest increase occurring between P0-3 and P7. 3. Thus catecholamine and TRH modulation of inspiratory-related XII nerve activity increases during the first two weeks of life; the potentiating effects of NE appear prior to those of TRH. 4. With rhythmically active, transverse medullary slices from mice up to 2 wk of age, it is now possible to study the development of XII motoneuron modulation as it relates to respiratory control of the upper airway.

Aging↗

PubMed1994

Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat.

1. We have hypothesized that pacemaker neurons in the pre-Bötzinger complex (pre-BötC) form the kernel for respiratory rhythm generation. A prediction of this hypothesis is that oscillatory behavior in some respiratory neurons could persist in the absence of synaptic transmission. In this study we used extracellular recording of neuronal activity in slice preparations from neonatal rat medulla that generate respiratory rhythm in vitro to determine 1) whether pacemaker properties are present in pre-BötC and unique to respiratory neurons, 2) whether pacemaker properties are common to all respiratory neurons, and 3) the spatiotemporal patterns of pacemaker neuron activity. 2. Whole cell recordings from respiratory neurons verified that bathing the slices in a low-Ca2+/high-Mg2+ solution (low-Ca2+ solution) eliminated endogenous respiratory synaptic inputs and electrically evoked synaptic inputs. 3. Sixty-three neurons spontaneously generated rhythmic bursts of action potentials in low-Ca2+ solution. After we switched to control solution to reactivate the respiratory network, these neurons were classified on the basis of their spike discharge patterns relative to the respiratory cycle as: 1) inspiratory (I) neurons (n = 41), 2) tonic expiratory (tonic E) neurons (n = 4), and 3) tonic neurons (n = 18). 4. In other experiments we tested I and tonic E neurons identified first in control solution for bursting behavior in low-Ca2+ solution. Several I neurons (n = 5 of 33), but none of the tonic E neurons (n = 0 of 13), continued to burst rhythmically. 5. Bursting and nonbursting respiratory neurons were distributed throughout the ventrolateral reticular formation within the pre-BötC as well as in the ventral respiratory group (VRG) immediately caudal to the pre-BötC. 6. We conclude that subpopulations of VRG neurons in vitro have rhythmic bursting properties when synaptic transmission is abolished. Respiratory neurons, especially I neurons, were the most prevalent class of bursting cells. Only a small percentage of respiratory neurons, however, had pacemaker properties. These findings are consistent with the hypothesis that the respiratory oscillator includes specialized neurons with intrinsic oscillatory properties.

Action Potentials↗

PubMed1993

Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids.

1. The involvement of excitatory amino acid (EAA) receptors in the generation of respiratory rhythm and transmission of inspiratory drive to hypoglossal (XII) motoneurons was examined in an in vitro neonatal rat medullary slice preparation. Slices generated rhythmic inspiratory activity in XII nerves. The role of EAAs in rhythm generation was determined by analyzing perturbations of respiratory network activity after bath application of EAA receptor antagonists or local microinjection of antagonists into the main column of respiratory neurons in the ventrolateral medulla (ventral respiratory group), particularly in the pre-Bötzinger complex (pre-BötC). The involvement of EAAs in drive transmission to XII motoneurons was examined by recording perturbations in XII nerve discharge or motoneuron synaptic inputs after microinjection of EAA receptor antagonists into either the XII motor nuclei or sites in the ventrolateral medulla containing interneurons of the drive transmission circuit. 2. Block of non-N-methyl-D-aspartate (non-NMDA) receptors by bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reversibly reduced XII nerve burst frequency and amplitude in a concentration-dependent manner, completely blocking respiratory motor output at concentrations > 4 microM. Activation of 2-amino-4-phosphonobutyric acid (AP-4)-sensitive receptors with D,L AP-4 reduced XII nerve burst amplitude by 30% but did not alter burst frequency. Block of NMDA receptor channels by bath application of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-iminemaleate (MK-801) did not perturb the frequency or amplitude of motor output. Inhibition of EAA uptake in the slices by bath application of dihydrokainic acid reversibly increased the frequency and amplitude of XII motor discharge. 3. Block of non-NMDA receptors at multiple sites along the main column of respiratory neurons in the ventrolateral medulla, including the pre-BötC, by unilateral microinjection of CNQX produced a dose-dependent, bilateral reduction in XII nerve burst amplitude without substantial perturbations of the frequency of respiratory oscillations. Block of non-NMDA receptors within the pre-BötC at sites ventral to amplitude altering sites produced a reduction in frequency and ultimately bilateral block of respiratory network oscillations. 4. Non-NMDA receptor block within the XII motor nucleus by unilateral microinjection of CNQX produced a dose-dependent reduction in ipsilateral XII nerve discharge amplitude without perturbing the frequency of respiratory oscillations. Perturbations of contralateral XII nerve burst amplitude were significantly smaller. NMDA channel block within the XII motor nucleus did not affect inspiratory burst amplitude, whereas activation of AP-4 receptors caused a 30% reduction in amplitude.

Action Potentials↗

PubMed1992

Coordination of wingbeat and respiration in the Canada goose. I. Passive wing flapping.

The effects of passive wing flapping on respiratory pattern were examined in decerebrate Canada geese. The birds were suspended dorsally with two spine clamps while the extended wings were continuously moved up and down with a device designed to reproduce actual wing flapping. Passive wing motion entrained respiration over limited ranges by both increasing and decreasing the respiratory period relative to rest. All ratios of wingbeat frequency to respiratory frequency seen during free flight (Soc. Neurosci. Abstr. 15: 391, 1989) were produced during passive wing flapping. In addition, the phase relationship between wingbeat frequency and respiratory frequency, inspiration starting near the peak of wing upstroke, was similar to that seen during free flight and was unaffected by perturbations of the wing-flapping cycle. Removal of all afferent activity from the wings did not affect the ability of continuous passive wing movement to entrain respiration. However, feedback from the wings was required to produce rapid within-breath shifts in the respiratory period in response to single wing flaps. In conclusion, although feedback from the chest wall/lung may be more important in producing entrainment during the stable conditions of passive wing flapping, wing-related feedback may be critically involved in mediating the rapid adjustments in respiratory pattern required to maintain coordination between wing and respiratory movements during free flight.

Afferent Pathways↗

PubMed1992

Coordination of wingbeat and respiration in birds. II. "Fictive" flight.

To determine whether an interaction between central respiratory and locomotor networks may be involved in the observed coordination of wingbeat and respiratory rhythms during free flight in birds, we examined the relationship between wingbeat and respiratory activity in decerebrate Canada geese and Pekin ducks before and after paralysis. Locomotor activity was induced through electrical stimulation of brain stem locomotor regions. Respiratory frequency (fv) was monitored via pneumotachography and intercostal electromyogram recordings before paralysis and via intercostal and cranial nerve IX electroneurogram recordings after paralysis. Wingbeat frequency (fW) was monitored using pectoralis major electromyogram recordings before, and electroneurogram recordings after, paralysis. Respiratory and cardiovascular responses of decerebrate birds during active (nonparalyzed) and "fictive" (paralyzed) wing activity were qualitatively similar to those of a variety of vertebrate species to exercise. As seen during free flight, wingbeat and respiratory rhythms were always coordinated during electrically induced wing activity. Before paralysis during active wing flapping, coupling ratios (fW/fv) of 1:1, 2:1, 3:1, and 4:1 (wingbeats per breath) were observed. After paralysis, fW and fv remained coupled; however, 1:1 coordination predominated. All animals tested (n = 9) showed 1:1 coordination. Two animals also showed brief periods of 2:1 coupling. It is clear that locomotor and respiratory networks interact on a central level to produce a synchronized output. The observation that the coordination between fW and fv differs in paralyzed and nonparalyzed birds suggests that peripheral feedback is involved in the modulation of a centrally derived coordination.

Animals↗

PubMed1991

Avian locomotion activated by brainstem infusion of neurotransmitter agonists and antagonists. I. Acetylcholine excitatory amino acids and substance P.

Previous studies have demonstrated that focal electrical stimulation of regions within the brainstem of a decerebrate bird will elicit all the normal patterns of avian locomotion. However, electrical stimulation can activate a variety of neuronal elements within the radius of effective current spread, including axons of passage traversing the stimulation point. To restrict activation to neuronal cell bodies within the immediate vicinity, we have utilized direct intracerebral injection of neurotransmitters, their agonists and antagonists, into identified brainstem locomotor regions. To undertake these studies, birds (geese or ducks) were placed in a stereotaxic frame and decerebrated under halothane anesthesia. After completion of surgery, several discrete locomotor regions were first identified with electrical microstimulation. Acetylcholine (ACh) and excitatory amino acid (EAA) agonists and antagonists, as well as Substance P were then slowly infused into each brainstem region. Any change in locomotor behavior was recorded by electromyographic techniques. When injected into a variety of sites, carbachol (an ACh nicotinic (AChN) and muscarinic (AChM) agonist) and pilocarpine (an AChM agonist) evoked locomotion, whereas atropine (an AChM antagonist) blocked locomotion. N-methyl-D-aspartate NMDA), but not glutamate, also elicited locomotion or reduced the current intensity threshold for electrically-evoked locomotion. The NMDA-induced locomotion evoked locomotion. The NMDA-induced locomotion could be blocked by the injection of glutamic acid diethyl ester (GDEE, an EAA antagonist) or D-2-amino-5-phosphonopentanoic acid (AP5) into the same site. Finally. Substance P also evoked locomotion. The above observations strongly suggest that brainstem electrically-stimulated locomotion in decerebrate birds is not due to activation of fibers traversing a brainstem locomotor region, but instead, is due to the activation of receptors located on neuronal cell bodies, dendrites or presynaptic terminals in the immediate vicinity of the micropipette tip. After correlating our findings with similar lamprey and mammalian studies, the comparable discoveries serve to underscore the suggestion that the neuroanatomical substrates underlying the brainstem control of locomotion appear to be highly conserved in all vertebrates.

Acetylcholine↗