Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:GABA is excitatory in adult vasopressinergic neuroendocrine cells. 2223 92

Oxytocin and its receptor (Oxtr) play a crucial role in the postnatal transition of neuronal GABA neurotransmission from excitatory to inhibitory, a developmental process known as the GABA switch. Using hippocampal neurons from Oxtr-null mice, we show that (1) Oxtr is necessary for the correct timing of the GABA switch by upregulating activity of the chloride cotransporter KCC2, (2) Oxtr, in a very early and narrow time window, directly modulates the functional activity of KCC2 by promoting its phosphorylation and insertion/stabilization at the neuronal surface, and (3) in the absence of Oxtr, electrophysiological alterations are recorded in mature neurons, a finding consistent with a reduced level of KCC2 and increased susceptibility to seizures observed in adult Oxtr-null mice. These data identify KCC2 as a key target of oxytocin in postnatal events that may be linked to pathogenesis of neurodevelopmental disorders.
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PMID:The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2. 2705 80

Autism spectrum disorder (ASD) and temporal lobe epilepsy exhibit remarkable comorbidity, but for reasons not clearly understood. To reveal a common pathophysiological mechanism, we here describe and characterize an in vitro epileptiform activity in the rat hippocampus that exhibits common features with in vivo activity in rodent ASD models. We discovered the development of this activity in the CA1 region of horizontal slices after prolonged interictal-like epileptiform activity in the CA3 region that was provoked by incubation in high potassium artificial cerebrospinal fluid. The CA1 epileptiform bursts were insensitive to blockers of glutamatergic transmission, and were carried by synaptic as well as extrasynaptic, tonically activated gamma-aminobutyric acid type A (GABA(A)) receptors. The bursts bear resemblance to in vivo gamma-oscillatory activity found in rat ASD models with respect to their gamma frequency spectrum, their origin (in the CA1), and their sensitivity to blockers of cation-chloride pumps (NKCC1 and KCC2), as well as to oxytocin. Considering this bursting activity as an in vitro model for studying comorbidity between epilepsy and ASD may help to disentangle the intricate interactions that underlie the comorbidity between both diseases and suggests that extrasynaptic tonic GABAergic transmission could represent a potential target for ASD.
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PMID:Gamma oscillatory activity in vitro: a model system to assess pathophysiological mechanisms of comorbidity between autism and epilepsy. 2931 12