Forskolin induces NMDA receptor-dependent potentiation at a central synapse in the leech

Kathryn B. Grey, Brian D. Burrell

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique for inducing chemical long-term potentiation (cLTP) that is N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin induces a similar potentiation in invertebrate synapses. Therefore, we examined whether forskolin plus rolipram treatment could induce potentiation at a known glutamatergic synapse in the leech (Hirudo sp.), specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of isolated ganglia with forskolin (50 μM) in conjunction with rolipram (0.1 μM) in Mg2+-free saline significantly potentiated the P-to-AP excitatory postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100 μM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to-AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis-(o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic cell, but not by BAPTA injection into the presynaptic neuron, indicating a requirement for postsynaptic elevation of intracellular Ca2+. Application of db-cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of protein kinase A, blocked forskolin-induced potentiation. Potentiation was also blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a requirement for activation of Ca2+/ calmodulin-dependent kinase II (CaMKII). Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking of glutamate receptors also plays a role in this form of synaptic plasticity. These experiments demonstrate that techniques used to induce cLTP in vertebrate synapses also induce NMDAR-dependent potentiation in the leech CNS and that many of the cellular processes that mediate LTP are conserved between vertebrate and invertebrate phyla.

Original languageEnglish (US)
Pages (from-to)2719-2724
Number of pages6
JournalJournal of Neurophysiology
Volume99
Issue number5
DOIs
StatePublished - May 1 2008

Fingerprint

Leeches
Colforsin
N-Methyl-D-Aspartate Receptors
Synapses
Rolipram
Vertebrates
Long-Term Potentiation
Invertebrates
Neurons
2-Amino-5-phosphonovalerate
Calcium-Calmodulin-Dependent Protein Kinases
Injections
Neuronal Plasticity
Phosphodiesterase Inhibitors
Botulinum Toxins
Excitatory Postsynaptic Potentials
Glutamate Receptors
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Ganglia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Forskolin induces NMDA receptor-dependent potentiation at a central synapse in the leech. / Grey, Kathryn B.; Burrell, Brian D.

In: Journal of Neurophysiology, Vol. 99, No. 5, 01.05.2008, p. 2719-2724.

Research output: Contribution to journalArticle

@article{c7dafa7cd1524942af1b35a02a25e48d,
title = "Forskolin induces NMDA receptor-dependent potentiation at a central synapse in the leech",
abstract = "In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique for inducing chemical long-term potentiation (cLTP) that is N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin induces a similar potentiation in invertebrate synapses. Therefore, we examined whether forskolin plus rolipram treatment could induce potentiation at a known glutamatergic synapse in the leech (Hirudo sp.), specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of isolated ganglia with forskolin (50 μM) in conjunction with rolipram (0.1 μM) in Mg2+-free saline significantly potentiated the P-to-AP excitatory postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100 μM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to-AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis-(o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic cell, but not by BAPTA injection into the presynaptic neuron, indicating a requirement for postsynaptic elevation of intracellular Ca2+. Application of db-cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of protein kinase A, blocked forskolin-induced potentiation. Potentiation was also blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a requirement for activation of Ca2+/ calmodulin-dependent kinase II (CaMKII). Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking of glutamate receptors also plays a role in this form of synaptic plasticity. These experiments demonstrate that techniques used to induce cLTP in vertebrate synapses also induce NMDAR-dependent potentiation in the leech CNS and that many of the cellular processes that mediate LTP are conserved between vertebrate and invertebrate phyla.",
author = "Grey, {Kathryn B.} and Burrell, {Brian D.}",
year = "2008",
month = "5",
day = "1",
doi = "10.1152/jn.00010.2008",
language = "English (US)",
volume = "99",
pages = "2719--2724",
journal = "Journal of Neurophysiology",
issn = "0022-3077",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Forskolin induces NMDA receptor-dependent potentiation at a central synapse in the leech

AU - Grey, Kathryn B.

AU - Burrell, Brian D.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique for inducing chemical long-term potentiation (cLTP) that is N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin induces a similar potentiation in invertebrate synapses. Therefore, we examined whether forskolin plus rolipram treatment could induce potentiation at a known glutamatergic synapse in the leech (Hirudo sp.), specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of isolated ganglia with forskolin (50 μM) in conjunction with rolipram (0.1 μM) in Mg2+-free saline significantly potentiated the P-to-AP excitatory postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100 μM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to-AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis-(o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic cell, but not by BAPTA injection into the presynaptic neuron, indicating a requirement for postsynaptic elevation of intracellular Ca2+. Application of db-cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of protein kinase A, blocked forskolin-induced potentiation. Potentiation was also blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a requirement for activation of Ca2+/ calmodulin-dependent kinase II (CaMKII). Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking of glutamate receptors also plays a role in this form of synaptic plasticity. These experiments demonstrate that techniques used to induce cLTP in vertebrate synapses also induce NMDAR-dependent potentiation in the leech CNS and that many of the cellular processes that mediate LTP are conserved between vertebrate and invertebrate phyla.

AB - In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique for inducing chemical long-term potentiation (cLTP) that is N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin induces a similar potentiation in invertebrate synapses. Therefore, we examined whether forskolin plus rolipram treatment could induce potentiation at a known glutamatergic synapse in the leech (Hirudo sp.), specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of isolated ganglia with forskolin (50 μM) in conjunction with rolipram (0.1 μM) in Mg2+-free saline significantly potentiated the P-to-AP excitatory postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100 μM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to-AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis-(o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic cell, but not by BAPTA injection into the presynaptic neuron, indicating a requirement for postsynaptic elevation of intracellular Ca2+. Application of db-cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of protein kinase A, blocked forskolin-induced potentiation. Potentiation was also blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a requirement for activation of Ca2+/ calmodulin-dependent kinase II (CaMKII). Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking of glutamate receptors also plays a role in this form of synaptic plasticity. These experiments demonstrate that techniques used to induce cLTP in vertebrate synapses also induce NMDAR-dependent potentiation in the leech CNS and that many of the cellular processes that mediate LTP are conserved between vertebrate and invertebrate phyla.

UR - http://www.scopus.com/inward/record.url?scp=47549091949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47549091949&partnerID=8YFLogxK

U2 - 10.1152/jn.00010.2008

DO - 10.1152/jn.00010.2008

M3 - Article

C2 - 18337371

AN - SCOPUS:47549091949

VL - 99

SP - 2719

EP - 2724

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 5

ER -