Pharmacological disinhibition enhances paced breathing following complete spinal cord injury in rats.

Respiratory dysfunction is one of the most devastating and life-threatening deficits that occurs following cervical spinal cord injury (SCI). Assisted breathing with mechanical ventilators is a necessary part of care for many cervical injured individuals, but it is also associated with increased risk of secondary complications such as infection, muscle atrophy and maladaptive plasticity. Pre-clinical studies with epidural stimulation (EDS) have identified it as an alternative/additional method to support adequate lung ventilation without mechanical assistance. The full potential of EDS, however, may be limited by spinal inhibitory mechanisms within the injured spinal cord. The goal of the present work is to assess the potential improvement for EDS in combination with pharmacological disinhibition of spinal circuits following complete high cervical SCI. All experiments were performed in decerebrate, unanesthetized, non-paralyzed (n = 13) and paralyzed (n = 8) adult Sprague-Dawley rats 6 h following a complete C1 transection. The combination of high-frequency EDS (HF-EDS) at the C4 spinal segment with intrathecal delivery of GABA and glycine receptors antagonists (GABAzine and strychnine, respectively) resulted in significantly increased phrenic motor output, tidal volume and amplitude of diaphragm electrical activity compared to HF-EDS alone. Thus, it appears that spinal fast inhibitory mechanisms limit phrenic motor output and present a new neuropharmacological target to improve paced breathing in individuals with cervical SCI.

Characteristics of the post-tetanic modification of synaptic transmission in the thalamocortical input of the somatosensory cortex in rats.

The development of both long-term post-tetanic potentiation and depression of focal evoked potentials by identified columns in the somatosensory cortex of unanesthetized rats was shown to occur in conditions of stimulation of their thalamocortical afferents. Trains of theta stimulation induced the phase-dependent development of post-tetanic potentiation after tetanization on the negative phase of the theta wave, while depression occurred after stimulation on the positive phase. Continuous tetanization produced potentiation only with stimulation at optimum amplitude and duration; extremely strong tetanization generally induced depression of responses to test stimuli, evidently because of activation of recurrent inhibition.