Activity dependent stimulation increases synaptic efficacy in spared pathways in an anesthetized rat model of spinal cord contusion injury

Background: Closed-loop neuromodulation systems have received increased attention in recent years as potential therapeutic approaches for treating neurological injury and disease. Objective: The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI). Methods: Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecutive 1-hour conditioning bouts for a total of 3 hours. At the end of each conditioning bout, changes in synaptic efficacy were assessed using intracortical microstimulation (ICMS) to examine the number of spikes evoked in spinal cord neurons during 5-minute test bouts. A multichannel microelectrode recording array was used to record cortically-evoked spike activity from multiple layers of the spinal cord. Results: The results showed that ADS resulted in an increase in cortically-evoked spikes in spinal cord neurons at specific combinations of spike-ISMS delays and numbers of pulses. Efficacy in descending motor pathways was increased throughout all dorsoventral depths of the hindlimb spinal cord. Conclusions: These results show that after an SCI, ADS can increase synaptic efficacy in spared pathways between motor cortex and spinal cord. This study provides further support for the potential of ADS therapy as an effective method for enhancing descending motor control after SCI

Presynaptic adrenergic facilitation of parasympathetic neurotransmission in sympathectomized rat smooth muscle

Parasympathetic innervation of rat eyelid tarsal smooth muscle normally inhibits sympathetic neurotransmission prejunctionally without significant direct postjunctional effects. Following surgical sympathectomy, parasympathetic stimulation elicits smooth muscle contraction. This study examined the relative contributions of cholinergic and adrenergic mechanisms mediating these contractions.Electrical stimulation of the superior salivatory nucleus, which activates tarsal muscle parasympathetic nerves, elicited large contractions at 2 days postsympathectomy, which were abolished by atropine and were decreased by 65 % by α1-adrenoceptor blockade or spinal cord transection.Contractions in response to direct cholinergic stimulation by bethanechol at 2 days postsympathectomy were increased following spinal cord transection (C2) and suppressed by the α1-adrenoceptor agonist phenylephrine, indicating that adrenoceptors on smooth muscle attenuate cholinergic contractions. However, phenylephrine infusion enhanced contractile responses to parasympathetic stimulation.Reverse transcription-polymerase chain reaction revealed α1D-adrenoceptor mRNA within pterygopalatine ganglia.At 5 weeks and 14 months postsympathectomy, adrenergic facilitation was significantly less than at 2 days, whereas prazosin-insensitive muscarinic contraction was increased.We conclude that degeneration of sympathetic innervation is followed rapidly by adrenoceptor-mediated prejunctional enhancement of parasympathetic nerve-smooth muscle neurotransmission, which occurs prior to neuroeffector junction formation as determined previously by electron microscopy. Subsequently, noradrenergic enhancement is diminished as cholinergic neurotransmission becomes established