Reduced GABAergic inhibition of kidney-related PVN neurons in streptozotocin-treated type 1 diabetic mouse

Activity of presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus is known to play an important role in the regulation of sympathetic outflow. Sympathetic overactivity is associated with many pathophysiological conditions such as diabetes mellitus and hypertension; however, the underlying synaptic mechanisms are poorly understood. In this study, we examined the GABAergic inhibitory synaptic control of kidney-related presympathetic PVN neurons in the streptozotocin-treated type 1 diabetic mouse model, using patch-clamp slice electrophysiology in combination with retrograde labeling. Type 1 diabetes resulted in decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs). Our data also demonstrated a reduction of mIPSC amplitude and mean inhibitory current without alteration of input resistance. Furthermore, our data revealed decreased tonic GABAergic inhibition of kidney-related PVN neurons in diabetic conditions, which was consistent with the observed increased excitability of the presympathetic PVN neurons. In summary, our data demonstrated decreased phasic and tonic inhibitory control of kidney-related presympathetic PVN neurons that suggest altered sympathetic circuitry in type 1 diabetes.