Robert P. Irwin

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The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-D-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250 microM) caused a concentration-dependent and(More)
The ability of NMDA to alter intracellular pH (pHi) was studied in fetal rat hippocampal neurons and glia using the pH-sensitive fluorescent indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). Brief exposure (60 sec) of hippocampal neurons to NMDA (2.5-250 microM) results in a rapid, and in most cells reversible, reduction in pHi,(More)
Pregnenolone sulfate and 15 related steroids were investigated for their effects on N-methyl-D-aspartate (NMDA)-induced elevations in intracellular Ca++ ([Ca++]i) in cultured rat hippocampal neurons by microspectrofluorimetry with the Ca(++)-sensitive indicator fura-2. Several pregn-5-ene steroids markedly potentiated NMDA-mediated [Ca++]i responses.(More)
Circadian oscillations in the suprachiasmatic nucleus (SCN) depend on transcriptional repression by Period (PER)1 and PER2 proteins within single cells and on vasoactive intestinal polypeptide (VIP) signaling between cells. Because VIP is released by SCN neurons in a circadian pattern, and, after photic stimulation, it has been suggested to play a role in(More)
Hyperexcited states, including depolarization block and depolarized low amplitude membrane oscillations (DLAMOs), have been observed in neurons of the suprachiasmatic nuclei (SCN), the site of the central mammalian circadian (~24-hour) clock. The causes and consequences of this hyperexcitation have not yet been determined. Here, we explore how individual(More)
We have recently reported that the majority of cultured rat cerebellar granule neurons undergo apoptosis when maintained in the presence of physiological concentrations of K+ (nondepolarizing conditions). We now report that exposure of cultured cerebellar granule neurons, maintained under nondepolarizing conditions, to the muscarinic cholinergic receptor(More)
Glutamate released from retinohypothalamic tract (RHT) synapses with suprachiasmatic nucleus (SCN) neurons induces phase changes in the circadian clock presumably by using Ca2+ as a second messenger. We used electrophysiological and Ca2+ imaging techniques to simultaneously record changes in the membrane potential and intracellular calcium concentration(More)
Presynaptic GABA(B) receptor activation inhibits glutamate release from retinohypothalamic tract (RHT) terminals in the suprachiasmatic nucleus (SCN). Voltage-clamp whole cell recordings from rat SCN neurons and optical recordings of Ca2+-sensitive fluorescent probes within RHT terminals were used to examine GABA(B)-receptor modulation of RHT transmission.(More)
Intercellular communication between gamma-aminobutyric acid (GABA)ergic suprachiasmatic nucleus (SCN) neurons facilitates light-induced phase changes and synchronization of individual neural oscillators within the SCN network. We used ratiometric Ca(2+) imaging techniques to record changes in the intracellular calcium concentration ([Ca(2+)](i)) to study(More)
Environmental synchronization of the endogenous mammalian circadian rhythm involves glutamatergic and GABAergic neurotransmission within the hypothalamic suprachiasmatic nucleus (SCN). The neuropeptide nociceptin/orphanin FQ (N/OFQ) inhibits light-induced phase shifts, evokes K(+)-currents and reduces the intracellular Ca(2+) concentration in SCN neurons.(More)