Spinal cord injury is associated with changes in synaptic properties of the mouse major pelvic ganglion.

Spinal cord injury (SCI) has substantial impacts on autonomic function. In part, SCI results in loss of normal autonomic activity that contributes to injury-associated pathology such as neurogenic bladder, bowel, and sexual dysfunction. Yet little is known of the impacts of SCI on peripheral autonomic neurons that directly innervate these target organs. In this study, we measured changes in synaptic properties of neurons of the mouse major pelvic ganglion (MPG) associated with acute and chronic SCI. Our data show that functional and physiological properties of synapses onto MPG neurons are altered after SCI and differ between acute and chronic injury. After acute injury excitatory postsynaptic potentials (EPSPs) show increased rise and decay time constants leading to overall broader and longer EPSPs, whereas in chronic-injured animals EPSPs are reduced in amplitude and show faster rise and decay leading to shorter EPSPs. Synaptic depression and low-pass filtering are also altered in injured animals. Finally, cholinergic currents are smaller in acute-injured animals but larger in chronic-injured animals relative to control animals. These changes in synaptic properties are associated with differences in nicotinic receptor subunit expression as well. MPG CHRNA3 mRNA levels decreased after injury, whereas CHRNA4 mRNAs increased. Furthermore, changes in the correlations of α- and ß-subunit mRNAs suggest that nicotinic receptor subtype composition is altered after injury. Taken together, our data demonstrate that peripheral autonomic neurons are fundamentally altered after SCI, suggesting that longer-term therapeutic approaches could target these neurons directly to potentially help ameliorate neurogenic target organ dysfunction.NEW & NOTEWORTHY Spinal cord injury (SCI) has substantial impacts on autonomic function, yet little is known of the impacts of SCI on autonomic neurons that directly innervate effectors impacted by injury. Here we investigated changes at the cellular level associated with SCI in neurons that are "downstream" of the central injury. An understanding of these off-target impacts of SCI ultimately will be critical in the context of effective restoration of function through neuromodulation of pharmacological therapeutic approaches.

Changes in excitability and ion channel expression in neurons of the major pelvic ganglion in female type II diabetic mice.

Bladder cystopathy and autonomic dysfunction are common complications of diabetes, and have been associated with changes in ganglionic transmission and some measures of neuronal excitability in male mice. To determine whether type II diabetes also impacts excitability of ganglionic neurons in females, we investigated neuronal excitability and firing properties, as well as underlying ion channel expression, in major pelvic ganglion (MPG) neurons in control, 10-week, and 21-week Leprdb/db mice. Type II diabetes in Leprdb/db animals caused a non-linear change in excitability and firing properties of MPG neurons. At 10 weeks, cells exhibited increased excitability as demonstrated by an increased likelihood of firing multiple spikes upon depolarization, decreased rebound spike latency, and overall narrower action potential half-widths as a result of increased depolarization and repolarization slopes. Conversely, at 21 weeks MPG neurons of Leprdb/db mice reversed these changes, with spiking patterns and action-potential properties largely returning to control levels. These changes are associated with numerous time-specific changes in calcium, sodium, and potassium channel subunit mRNA levels. However, Principal Components Analysis of channel expression patterns revealed that rectification of excitability is not simply a return to control levels, but rather a distinct ion channel expression profile in 21-week Leprdb/db neurons. These data indicate that type II diabetes can impact the excitability of post-ganglionic, autonomic neurons of female mice, and suggest that the non-linear progression of these properties with diabetes may be the result of compensatory changes in channel expression that act to rectify disrupted firing patterns of Leprdb/db MPG neurons.