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Functional and Morphological Assessment of Diaphragm Innervation by Phrenic Motor Neurons
Published on: May 25, 2015
Neurochemical phenotypes of MRF neurons influencing diaphragm and rectus abdominis activity
I Billig1, J P Card, B J Yates
1Department of Otolaryngology, University of Pittsburgh, Pennsylvania 15213, USA.
Abstract:
In prior studies that used transneuronal transport of isogenic recombinants of pseudorabies virus, we established that medial medullary reticular formation (MRF) neurons sent collateralized projections to both diaphragm and abdominal muscle motoneurons. Furthermore, inactivation of MRF neurons in cats and ferrets increased the excitability of diaphragm and abdominal motoneurons, suggesting that MRF neurons controlling respiratory activity are inhibitory. To test this hypothesis, the present study determined the neurochemical phenotypes of MRF premotor respiratory neurons in the ferret by using immunohistochemical procedures. Dual-labeling immunohistochemistry combining pseudorabies virus injections into respiratory muscles with the detection of glutamic acid decarboxylase-like immunoreactive and glutamate-like immunoreactive cells showed that both GABAergic and glutamatergic MRF neurons project to respiratory motoneurons, although the latter are more common. These data suggest that the role of the MRF in respiratory regulation is multifaceted, as this region provides both inhibitory and excitatory influences on motoneuron activity.
Insights
The medial medullary reticular formation (MRF) contains both inhibitory and excitatory neurons that influence respiratory muscles. These MRF neurons project to diaphragm and abdominal motoneurons, indicating a complex role in breathing control.
Area of Science:
- Neuroscience
- Respiratory Physiology
Background:
- Previous studies indicated medial medullary reticular formation (MRF) neurons project to respiratory motoneurons.
- Inactivation of MRF neurons increased motoneuron excitability, suggesting inhibitory control of respiration.
Purpose of the Study:
- To determine the neurochemical phenotypes of MRF premotor respiratory neurons in ferrets.
- To investigate the specific neurotransmitters involved in MRF's respiratory control.
Main Methods:
- Utilized transneuronal transport of pseudorabies virus for neuronal tracing.
- Employed dual-labeling immunohistochemistry to identify neurotransmitters.
- Injected pseudorabies virus into respiratory muscles and detected GABAergic and glutamatergic cells.
Main Results:
- Identified both GABAergic (inhibitory) and glutamatergic (excitatory) MRF neurons projecting to respiratory motoneurons.
- Found a higher prevalence of glutamatergic projections compared to GABAergic ones.
- Confirmed collateralized projections from MRF to both diaphragm and abdominal motoneurons.
Conclusions:
- MRF neurons utilize both GABA and glutamate to modulate respiratory motoneuron activity.
- The MRF exerts multifaceted control over respiration, providing both inhibitory and excitatory influences.
- These findings elucidate the complex neurochemical basis of respiratory regulation originating in the MRF.

