Key result
Silencing V2a neurons in adult mice resulted in a 9.3-fold increase in trapezius and 7.5-fold increase in scalene muscle activity at rest, demonstrating that V2a neurons constrain extradiaphragmatic respiratory muscle activity.
Why the study?
Little is understood about how spinal and pontomedullary networks modulate respiratory motor neuron activity to produce different patterns across behaviors or following disease or injury.
Does chemogenetic inhibition of V2a neurons alter respiratory rhythm and extradiaphragmatic muscle activity in mice?
Does chemogenetic inhibition of V2a neurons alter respiratory rhythm and extradiaphragmatic muscle activity in mice?
Effect estimate: 9.3-fold increase in trapezius and 7.5-fold increase in scalene activity
p-value: p=<0.05
V2a neurons are required for respiratory rhythm generation in neonatal mice but serve to constrain extradiaphragmatic respiratory muscle activity at rest in adult mice.
Hypothesis-generating for V2a modulation in respiratory disorders; requires validation in higher species before clinical relevance.
Breathing requires precise control of respiratory muscles to ensure adequate ventilation. Neurons within discrete regions of the brainstem produce oscillatory activity to control the frequency of breathing. Less is understood about how spinal and pontomedullary networks modulate the activity of respiratory motor neurons to produce different patterns of activity during different behaviors (i.e., during exercise, coughing, swallowing, vocalizing, or at rest) or following disease or injury. Here, we use a chemogenetic approach to inhibit the activity of glutamatergic V2a neurons in the brainstem and spinal cord of neonatal and adult mice to assess their potential roles in respiratory rhythm generation and patterning respiratory muscle activity. Using whole-body plethysmography (WBP), we show that V2a neuron function is required in neonatal mice to maintain the frequency and regularity of respiratory rhythm. However, silencing V2a neurons in adult mice increases respiratory frequency and ventilation, without affecting regularity. Thus, the excitatory drive provided by V2a neurons is less critical for respiratory rhythm generation in adult compared to neonatal mice. In addition, we used simultaneous EMG recordings of the diaphragm and extradiaphragmatic respiratory muscles in conscious adult mice to examine the role of V2a neurons in patterning respiratory muscle activity. We find that silencing V2a neurons activates extradiaphragmatic respiratory muscles at rest, when they are normally inactive, with little impact on diaphragm activity. Thus, our results indicate that V2a neurons participate in a circuit that serves to constrain the activity of extradiaphragmatic respiratory muscles so that they are active only when needed.
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Jensen et al. (2019) studied Healthy. Chemogenetic inhibition of V2a neurons (CNO) vs. Vehicle injection and non-DREADD expressing control mice was evaluated on Extradiaphragmatic respiratory muscle (trapezius and scalene) activity at rest (9.3-fold increase in trapezius and 7.5-fold increase in scalene activity, p=<0.05). Silencing V2a neurons in adult mice resulted in a 9.3-fold increase in trapezius and 7.5-fold increase in scalene muscle activity at rest, demonstrating that V2a neurons constrain extradiaphragmatic respiratory muscle activity.
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