The Journal of neuroscience : the official journal of the Society for Neuroscience

Synapses on sympathetic neurons and parasympathetic neurons differ in their vulnerability to diabetes.

PMID 24966386


Synapses in autonomic ganglia represent the final output of various CNS structures that regulate the function of the periphery. Normally, these excitatory cholinergic-nicotinic synapses produce large suprathreshold EPSPs on sympathetic and parasympathetic neurons to convey signals from the CNS. However, in certain disease states, synaptic transmission in autonomic ganglia is depressed and the periphery becomes deregulated. For example, previous work demonstrated that hyperglycemia depresses EPSPs on sympathetic neurons and disrupts sympathetic reflexes by causing an ROS-dependent inactivation of the postsynaptic nAChRs. What is not clear, however, is whether some autonomic neurons are more vulnerable to hyperglycemia than others. One possibility is that sympathetic neurons may be more prone than cholinergic parasympathetic neurons to hyperglycemia-induced elevations in cytosolic ROS because sympathetic neurons contain several pro-oxidant molecules involved in noradrenaline metabolism. To test this hypothesis, we recorded synaptic transmission from different mouse sympathetic and parasympathetic ganglia, as well as from the adrenal medulla. In addition, we used cellular imaging to measure hyperglycemia-induced changes in cytosolic ROS and whole-cell recordings to measure the use-dependent rundown of ACh-evoked currents. Our results demonstrate that hyperglycemia depresses synaptic transmission on sympathetic neurons and adrenal chromaffin cells and elevates cytosolic ROS. Conversely, hyperglycemia has little effect on synaptic transmission at synapses on parasympathetic neurons. We conclude that sympathetic neurons and adrenal chromaffin cells are more vulnerable to diabetes than parasympathetic neurons, a finding that may have implications for both long-term diabetic autonomic neuropathies and insulin-induced hypoglycemia, a serious complication of diabetes.