Photolytically released nitric oxide produces a delayed but persistent suppression of LTP in area CA1 of the rat hippocampal slice

Abstract

The role of nitric oxide (NO) in the induction of N-methylª-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) remains controversial. Based on observations that pharmacological blockade of nitric oxide synthase (NOS) or sequestration of NO impair the induction of LTP (O'Dell et al. 1991;Schuman & Madison, 1991;Haley et al. 1992) and that exogenous application of NO or NO donors induces potentiation (Bohme et al. 1991;Bon et al. 1992;Zhuo et al. 1993;Arancio et al. 1996), it has been claimed that NO may serve as a retrograde messenger during the induction of LTP. However, this view has been challenged by studies from several laboratories showing that neither blockade of NOS (Kato & Zorumski, 1993;Bannerman et al. 1994;Cummings et al. 1994;Kirkwood & Bear, 1994) nor exogenous application of NO or NO donors (Boulton et al. 1994;Murphy et al. 1994) affects the induction of LTP. Under certain experimental conditions, namely in slices prepared from young rats (5-7 weeks of age) and maintained at room temperature (•24°C), we have found it possible to block the induction of LTP with antagonists of NOS. However, if the experiments were repeated in slices maintained at a more physiological temperature (•30°C), or in slices prepared from adult rats, then blockade of NOS did not affect the induction of LTP (Williams et al. 1993). In further experiments, we used a caged form of NO in an attempt to induce LTP by pairing synaptic activation with photolytic release of NO (Murphy et al. 1994). These experiments were performed under the same conditions (young animals, low temperature) as those in which we had previously shown that NOS blockade impaired the induction of LTP. Pairing tetanic stimulation with exposure to NO, in the presence of the NMDA receptor antagonist ª(−)-2-amino-5-phosphonopentanoic acid (ª-AP5) did not induce LTP, a result suggesting that even in young animals NO is unlikely to be involved in the induction of LTP (Murphy et al. 1994). However, we noted that exposure to photolytically released NO affected the outcome of subsequent high-frequency trains. Specifically, after washout of AP5 and caged NO, slices previously exposed to concentrations of NO of less than 1 ìÒ expressed normal LTP, whereas those exposed to higher concentrations showed a decrease in the magnitude of

A Nitric Oxide-Independent and β-Adrenergic Receptor-Sensitive Form of Metaplasticity Limits θ-Frequency Stimulation-Induced LTP in the Hippocampal CA1 Region

“…Because nitric oxide synthase (NOS) inhibitors can both prevent the inhibition of LTP induction produced by transient NMDA receptor activation (Izumi et al 1992a) and facilitate NMDA receptor-mediated synaptic currents in CA1 pyramidal cells (Kato and Zorumski 1993), it has been suggested that some forms of metaplasticity may arise from a NO-dependent, negative-feedback modulation of NMDA receptors (Abraham and Tate 1997) or other targets (Zorumski and Izumi 1998). Consistent with this notion, Murphy and Bliss (1999) have recently shown that a brief pulse of photolytically released NO induces both a long-lasting depression of NMDA receptormediated synaptic potentials and a persistent inhibition of LTP induction in the CA1 region of hippocampal slices.…”

“…Because previous studies have suggested that a persistent depression of NMDA receptor-mediated synaptic responses (Selig et al 1995), perhaps mediated by NO (Murphy and Bliss 1999), may be involved in at least some forms of metaplasticity . Whereas 75 pulses of 5-Hz stimulation induces no further potentiation of synaptic transmission ( ; data from B), both 300 pulses of 20-Hz stimulation (᭡, N = 6, fEPSPs potentiated to 121.5 ± 5.3% of the potentiated baseline) and two 1-sec-long trains of 100-Hz stimulation (᭹, N = 9, fEPSPs potentiated to 140.9 ± 6.1% of the potentiated baseline) induce significant levels of additional LTP (P < 0.5, Student-Newman-Keuls test).…”

Two sides to long-term potentiation: a view towards reconciliation

“…Bohme et al [81] first demonstrated that NO donors persistently potentiated synaptic responses; similar effects were later confirmed using NO donors, free NO, and photoactivated NO [80][81][82][83]89,90,92,103,104]. By contrast, two groups have failed to elicit LTP with NO application [110][111][112]. Exogenous NO, therefore, appears to have varied effects on synaptic responses across studies.…”

Biotinylated Photocleavable Polyethylenimine: Capture and Triggered Release of Nucleic Acids from Solid Supports

“…Photolabile protecting groups function by rendering a molecule of interest inert until photolysis, and have been used extensively since their introduction in 1962 (1) for controlled release and kinetic studies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). For biological systems, this approach allows control of concentration, location, and timing of the compound's release into a system.…”