Concurrent Inhibition and Excitation of Phrenic Motoneurons during Inspiration: Phase-Specific Control of Excitability

Abstract

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.

Inspiratory augmenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes

“…Opiate-mediated disinhibition exists in the hippocampus as discussed above (Bramham and Sarvey, 1996;Jin and Chavkin, 1999;Akaishi et al, 2000) and has been also observed in other brain areas, such as the periaqueductal gray (Vaughan et al, 1997) and the rostral ventrolateral medulla (Hayar and Guyenet, 1998). GABAergic input to phrenic motor neurons during inspiration has been demonstrated by Parkis et al (1999). GABAergic terminals have also been identified by light microscopy near phrenic motor neurons (Zhan et al, 1989).…”

Patterns of Phrenic Nerve Discharge after Complete High Cervical Spinal Cord Injury in the Decerebrate Rat

“…42,[64][65][66][67][68][69][70][71][72] For example, local blockade of GABA synthesis (by application of anti-glutamate decarboxylase 65/67 siRNA) in the vicinity of the phrenic nucleus leads to increasing tonic and phasic activity in PhN discharge on the side of treatment. 71 It has been shown that tonic inhibition in spinal ventral horn interneurons is mediated by α5 subunit-containing GABA A receptors.…”

Synaptic Control of Motoneuronal Excitability

“…Inhibitory synaptic control of excitability during the active phase will affect the timing of burst onset and offset (affecting onset of muscle contraction and relaxation), firing pattern, and recruitment order (961,969,1049,1377,1379). Inhibitory inputs during the quiescent phase in a motoneuron, e.g., during the expiratory phase in an inspiratory neuron, will reduce the probability of spurious, and inappropriate, activation (1049).…”

“…Inhibition may also provide phase-specific control of motoneuron gain, as suggested by the observation of a phasic inspiratory inhibition of phrenic motoneurons that matches the shape and time course of their inspiratory excitatory drive (961). Because phrenic motoneurons (444), like most motoneurons (292,1084,1143,1221,1394), participate in multiple behaviors, such a mechanism may contribute to the optimization of motoneuron excitability for different motor tasks.…”