Disproportionate loss of excitatory inputs to smaller phrenic motor neurons following cervical spinal hemisection

Citations Over TimeTop 21% of 2020 papers

Abstract

Excitatory glutamatergic input mediating inspiratory drive to phrenic motor neurons (PhMNs) emanates primarily from the ipsilateral ventrolateral medulla. Unilateral C2 hemisection (C2SH) disrupts this excitatory input, resulting in cessation of inspiratory-related diaphragm muscle (DIAm) activity. In contrast, after C2SH, higher force, non-ventilatory DIAm activity persists. Inspiratory behaviours require recruitment of only smaller PhMNs, whereas with more forceful expulsive/straining behaviours, larger PhMNs are recruited. Accordingly, we hypothesize that C2SH primarily disrupts glutamatergic synaptic inputs to smaller PhMNs, whereas glutamatergic synaptic inputs to larger PhMNs are preserved. We examined changes in glutamatergic presynaptic input onto retrogradely labelled PhMNs using immunohistochemistry for VGLUT1 and VGLUT2. We found that 7 days after C2SH there was an ∼60% reduction in glutamatergic inputs to smaller PhMNs compared with an ∼35% reduction at larger PhMNs. These results are consistent with a more pronounced impact of C2SH on inspiratory behaviours of the DIAm, and the preservation of higher force behaviours after C2SH. These results indicate that the source of glutamatergic synaptic input to PhMNs varies depending on motor neuron size and reflects different functional control - perhaps separate central pattern generator and premotor circuits. For smaller PhMNs, the central pattern generator for inspiration is located in the pre-Bötzinger complex and premotor neurons in the ventrolateral medulla, sending predominantly ipsilateral projections via the dorsolateral funiculus. C2SH disrupts this glutamatergic input. For larger PhMNs, a large proportion of excitatory inputs appear to exist below the C2 level or from contralateral regions of the brainstem and spinal cord.

Related Papers

• → Aging affects the number and morphological heterogeneity of rat phrenic motor neurons and phrenic motor axons(2023)16 cited
• → Disproportionate loss of excitatory inputs to smaller phrenic motor neurons following cervical spinal hemisection(2020)21 cited
• → Influence of constituents of country liquor on the induced toxicity of some muscle relaxants in mice and phrenic nerve diaphragm preparations of rats: a preliminary report.(1980)1 cited
• → Presence of neuronal cell bodies in the sympathetic pressor areas of dorsal and ventrolateral medulla inhibiting phrenic nerve discharge in cats(1992)5 cited
• → ADAPTATIONS OF RAT PHRENIC MOTONEURONS TO INACTIVITY 130(1997)