title: GABA is excitatory in adult vasopressinergic neuroendocrine cells.
abstract: Neuronal excitability in the adult brain is controlled by a balance between synaptic excitation and inhibition mediated by glutamate and GABA, respectively. While generally inhibitory in the adult brain, GABA(A) receptor activation is excitatory under certain conditions in which the GABA reversal potential is shifted positive due to intracellular Cl(-) accumulation, such as during early postnatal development and brain injury. However, the conditions under which GABA is excitatory are generally either transitory or pathological. Here, we reveal GABAergic synaptic inputs to be uniformly excitatory in vasopressin (VP)-secreting magnocellular neurons in the adult hypothalamus under normal conditions. The GABA reversal potential (E(GABA)) was positive to resting potential and spike threshold in VP neurons, but not in oxytocin (OT)-secreting neurons. The VP neurons lacked expression of the K(+)-Cl(-) cotransporter 2 (KCC2), the predominant Cl(-) exporter in the adult brain. The E(GABA) was unaffected by inhibition of KCC2 in VP neurons, but was shifted positive in OT neurons, which express KCC2. Alternatively, inhibition of the Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1), a Cl(-) importer expressed in most cell types mainly during postnatal development, caused a negative shift in E(GABA) in VP neurons, but had no effect on GABA currents in OT neurons. GABA(A) receptor blockade caused a decrease in the firing rate of VP neurons, but an increase in firing in OT neurons. Our findings demonstrate that GABA is excitatory in adult VP neurons, suggesting that the classical excitation/inhibition paradigm of synaptic glutamate and GABA control of neuronal excitability does not apply to VP neurons.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA.
authors.forename: Juhee
authors.initials: J
authors.lastname: Haam
authors.forename: Ion R
authors.initials: IR
authors.lastname: Popescu
authors.forename: Linda A
authors.initials: LA
authors.lastname: Morton
authors.forename: Katalin C
authors.initials: KC
authors.lastname: Halmos
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Teruyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Tasker
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D059330:GABAergic Neurons / Q000502:physiology; D008297:Male; D055099:Neuroendocrine Cells / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000166:cytology / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D014667:Vasopressins; D005680:gamma-Aminobutyric Acid