PACAP-38 Enhances Excitatory Synaptic Transmission in the Rat Hippocampal CA1 Region

Roberto, Marisa; Brunelli, Marcello

doi:10.1101/lm.34200

Cited by 43 publications

(40 citation statements)

References 49 publications

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“…Previously, we found that 0.05 nM PACAP-38 produced a long-lasting enhancement of basal CA1 fEPSPs and that this enhancement was occluded by previous induction of LTP by high frequency stimulation (HFS) (Roberto and Brunelli 2000). In the present study, we examined the converse experiment (i.e., whether previous treatment with PACAP-38 would occlude LTP).…”

Section: Tetanic Stimulation Fails To Induce Ltp After Pacap-38-inducmentioning

confidence: 88%

“…Previously, we reported that brief bath application of 0.05 nM of PACAP-38 induced a long-lasting enhancement of the Schaffer collateral-commissural CA1 fEPSP, whereas PACAP-38 produced only a transient increase in the evoked responses after LTP was saturated (Roberto and Brunelli 2000). In those studies atropine blocked both facilitatory effects (Roberto and Brunelli 2000).…”

Section: Discussionmentioning

confidence: 99%

“…3). Previously, we demonstrated that 0.05 nM PACAP-38-induced a long-lasting enhancement of basal CA1 fEPSPs, which was mediated by the activation of muscarinic receptors, because atropine blocked the PACAP-38 effect (Roberto and Brunelli 2000). The effect of PACAP-38 in the presence of APV was significantly different than the effect of PACAP-38 in the presence of atropine (1 µM) (P&thuinsp;< 0.05).…”

Section: Pacap-38-induced Enhancement Of Ca1 Fepsps Is Partially Blocmentioning

confidence: 95%

“…Atropine, a muscarinic receptor antagonist, blocked the PACAP-induced enhancement of the CA1 fEPSP, suggesting that the PACAP-38 action is mediated by cholinergic muscarinic receptors (Roberto and Brunelli 2000). The PACAP-38 interaction with muscarinic receptors suggests a role of the peptide in learning and memory.…”

mentioning

confidence: 98%

“…Recently, we found that a relatively low concentration (0.05 nM) of PACAP-38 enhances the CA1 fEPSPs during baseline synaptic transmission, but not after the induction of long-term potentiation (LTP) produced by tetanic stimulation (Roberto and Brunelli 2000). Atropine, a muscarinic receptor antagonist, blocked the PACAP-induced enhancement of the CA1 fEPSP, suggesting that the PACAP-38 action is mediated by cholinergic muscarinic receptors (Roberto and Brunelli 2000).…”

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confidence: 99%

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Differential Effects of PACAP-38 on Synaptic Responses in Rat Hippocampal CA1 Region

Roberto

Scuri²,

Brunelli³

2001

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Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a member of the vasointestinal polypeptide (VIP)/secretin/glucagon family of neuropeptides for which neuroregulatory functions have been postulated. PACAP-38 receptors are expressed in different brain regions, including hippocampus. In this study, we examined the dose-dependent effects of PACAP-38 on the excitatory postsynaptic field potential (fEPSP) evoked at the Schaffer collateral-CA1 synapse in rat hippocampal slices. Bath application of low dose (0.05 nM) of PACAP-38 induced long-lasting facilitation of the fEPSP. This enhancement was blocked by the cholinergic receptor antagonist atropine and partially by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) and therefore, shares a common mechanism with LTP. In contrast, a high dose (1 µM) of PACAP-38 induced a persistent depression of the fEPSP that was not blocked by antagonists of cholinergic receptors (i.e., atropine and mecamylamine), adenosine receptors (i.e., DCPCX), or glutamatergic NMDA receptors (APV). Intermediate doses (0.1-0.5 µM) of PACAP-38 produced an initial decrease of the fEPSP followed by an enhancement. This decrease was not blocked by atropine whereas the facilitation was. These results show that PACAP-38 modulates CA1 synaptic transmission in a dose-dependent manner and that the peptide interacts with cholinergic and glutamatergic systems.Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a 38-amino acid peptide that was first isolated from ovine hypothalamus for its ability to stimulate adenylyl cyclase in rat anterior pituitary cells (Arimura 1992). PACAP-38 exhibits high sequence identity with vasoactive intestinal peptide (VIP), distinguishing PACAP-38 as a member of the VIP-secretin-glucagon family of peptides. The aminoacid sequence of PACAP-38 has been remarkably conserved during evolution, suggesting that PACAP-38 regulates important physiological functions (Arimura 1992;Masuo et al. 1993). Two receptors for PACAP-38 have been identified: type I receptors, which are positively coupled to adenylyl cyclase and phospholipase C, and type II receptors, which have only been linked to adenylyl cyclase (Spengler et al. 1993). PACAP-38 receptors are mainly distributed in the central nervous system including the hippocampus (Masuo et al. 1992(Masuo et al. , 1993.PACAP-38 modulates synaptic activity in several neuronal regions. For example, PACAP-38 enhances in a dosedependent manner the spontaneous release of acetylcholine (ACh) from septal cholinergic fibers in the dorsal hippocampus (Masuo et al. 1993). An excitatory action of PACAP-38 on glutamatergic N-methyl-D-aspartate (NMDA) receptors has also been reported in cortical neurons (Martin et al. 1995;Stella and Magistretti 1996;Liu and Madsen 1997) and in sympathetic preganglionic neurons of neonatal rat (Lai et al. 1997;Wu and Dun 1997). In addition, a high concentration of PACAP-38 (1-3 µM) induces a long-lasting depression of the field excitatory postsynaptic potential (fEPSP) at hippocampal ...

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Section: Tetanic Stimulation Fails To Induce Ltp After Pacap-38-inducmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Pacap-38-induced Enhancement Of Ca1 Fepsps Is Partially Blocmentioning

confidence: 95%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Differential Effects of PACAP-38 on Synaptic Responses in Rat Hippocampal CA1 Region

Roberto

Scuri²,

Brunelli³

2001

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Modulation of AMPA receptor‐mediated ion current by pituitary adenylate cyclase‐activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus

et al. 2008

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Pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotrophic and neuromodulatory peptide, was recently shown to enhance NMDA receptor-mediated currents in the hippocampus (Macdonald, et al. 2005. J Neurosci 25:11374-11384). To check if PACAP might also modulate AMPA receptor function, we tested its effects on AMPA receptor-mediated synaptic currents on CA1 pyramidal neurons, using the patch clamp technique on hippocampal slices. In the presence of the NMDA antagonist D-AP5, PACAP (10 nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of Schaffer collaterals. Following a paired-pulse stimulation protocol, the paired-pulse ratio was unaffected in most neurons, suggesting that the AMPA-mediated EPSC was modulated by PACAP mainly at a postsynaptic level. PACAP also modulated the currents induced on CA1 pyramidal neurons by applications of either glutamate or AMPA. The effects of PACAP were dose-dependent: at a 0.5 nM dose, PACAP increased AMPA-mediated current; such effect was blocked by PACAP 6-38, a selective antagonist of PAC1 receptors. The enhancement of AMPA-mediated current by PACAP 0.5 nM was abolished when cAMPS-Rp, a PKA inhibitor, was added to the intracellular solution. At a 10 nM concentration, PACAP reduced AMPA-mediated current; such effect was not blocked by PACAP 6-38. The inhibitory effect of 10 nM PACAP was mimicked by Bay 55-9837 (a selective agonist of VPAC2 receptors), persisted in the presence of intracellular BAPTA and was abolished by intracellular cAMPS-Rp. Stimulation-evoked EPSCs in CA1 neurons were significantly reduced following application of the PAC1 antagonist PACAP 6-38; this result indicates that PAC1 receptors in the CA1 region are tonically activated by endogenous PACAP and enhance CA3-CA1 synaptic transmission. Our results show that PACAP differentially modulates AMPA receptor-mediated current in CA1 pyramidal neurons by activation of PAC1 and VPAC2 receptors, both involving the cAMP/PKA pathway; the functional significance will be discussed in light of the multiple effects exerted by PACAP on the CA3-CA1 synapse at different levels.

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Pituitary Adenylate Cyclase-Activating Polypeptide Enhances Ca2+-Dependent Neurotransmitter Release from PC12 Cells and Cultured Cerebellar Granule Cells without Affecting Intracellular Ca2+ Mobilization

Aoyagi

Takahashi

2001

Biochemical and Biophysical Research Communications

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PACAP-38 Enhances Excitatory Synaptic Transmission in the Rat Hippocampal CA1 Region

Cited by 43 publications

References 49 publications

Differential Effects of PACAP-38 on Synaptic Responses in Rat Hippocampal CA1 Region

Differential Effects of PACAP-38 on Synaptic Responses in Rat Hippocampal CA1 Region

Modulation of AMPA receptor‐mediated ion current by pituitary adenylate cyclase‐activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus

Pituitary Adenylate Cyclase-Activating Polypeptide Enhances Ca2+-Dependent Neurotransmitter Release from PC12 Cells and Cultured Cerebellar Granule Cells without Affecting Intracellular Ca2+ Mobilization

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