Diminished GABAergic synaptic function in paraventricular (PVN) and supraoptic (SON) neurons in diabetic rats.

Diabetes mellitus is associated with altered neuroendocrine and autonomic control, resulting in increased levels of vasopressin and altered volume and baroreflex sensitivity, among others. While recent data support increased activity in the SON/PVN during diabetes (Zheng et al 2002), the cellular substrates and mechanisms underlying these changes are still unknown. The aim of this study was to determine if changes in GABAergic neurotransmission in SON/PVN neurons contribute to altered neuroendocrine and autonomic homeostasis in diabetic rats. Patch clamp recordings were obtained from preautonomic (retrogradely labeled PVN‐RVLM projecting) and magnocellular neurosecretory (MNCs) SON/PVN neurons in hypothalamic slices obtained from control and STZ‐induced diabetic rats. The frequency and amplitude of GABAA spontaneous inhibitory postsynaptic currents (sIPSCs) in PVN‐RVLM neurons decreased significantly in diabetic rats (82.3% and 40.7%, respectively, P<0.01). On the other hand, no changes were observed in MNCs. Repetitive activation of GABAergic synapses with extracellular stimulation also revealed smaller evoked GABA IPSCs (63.64 %change, P< 0.01), along with a higher degree of synaptic failures (72.7% change, P< 0.01) in PVN‐RVLM neurons of diabetic rats. Interestingly, a similar decrease in evoked GABAergic IPSCs was observed in MNCs. Our results indicate that GABAergic inhibitory function in preautonomic and MNCs PVN/SON neurons is diminished in diabetic rats, a mechanism that may contribute to enhanced vasopressin and altered autonomic reflex function during diabetes. Supported by NIH RO1 HL68725 (JES)