Co-induction of LTP and LTD and its regulation by protein kinases and phosphatases

Kathryn B. Grey, Brian D. Burrell

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The cellular properties of long-term potentiation (LTP) following pairing of pre- and postsynaptic activity were examined at a known glutamatergic synapse in the leech, specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Stimulation of the presynaptic P cell (25 Hz) concurrent with a 2 nA depolarization of the postsynaptic AP cell significantly potentiated the P-to-AP excitatory postsynaptic potential (EPSP) in an N-methyl-D-aspartate receptor (NMDAR)-dependent manner based on inhibitory effects of the NMDAR antagonist MK801 and inhibition of the NMDAR glycine binding site by 7-chlorokynurenic acid. LTP was blocked by injection of bis-(o-aminophenoxy)-N, N,N′,N′-tetraacetic acid (BAPTA) into the postsynaptic (AP) cell, indicating a requirement for postsynaptic elevation of intracellular Ca 2+. Autocamtide-2-related inhibitory peptide (AIP), a specific inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), and Rp-cAMP, an inhibitor of protein kinase A (PKA), also blocked pairing-induced potentiation, indicating a requirement for activation of CaMKII and PKA. Interestingly, application of AIP during pairing resulted in significantly depressed synaptic transmission. Co-application of AIP with the protein phosphatase inhibitor okadaic acid restored synaptic transmission to baseline levels, suggesting an interaction between CaMKII and protein phosphatases during induction of activity-dependent synaptic plasticity. When postsynaptic activity preceded presynaptic activity, NMDAR-dependent long-term depression (LTD) was observed that was blocked by okadaic acid. Postsynaptic injection of botulinum toxin blocked P-to-AP potentiation while postsynaptic injection of pep2-SVKI, an inhibitor of AMPA receptor endocytosis, inhibited LTD, supporting the hypothesis that glutamate receptor trafficking contributes to both LTP and LTD at the P-to-AP synapse in the leech.

Original languageEnglish (US)
Pages (from-to)2737-2746
Number of pages10
JournalJournal of Neurophysiology
Volume103
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Long-Term Potentiation
Phosphoprotein Phosphatases
N-Methyl-D-Aspartate Receptors
Protein Kinases
Leeches
Okadaic Acid
Calcium-Calmodulin-Dependent Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Synaptic Transmission
Synapses
Peptides
Injections
Neuronal Plasticity
AMPA Receptors
Botulinum Toxins
Excitatory Postsynaptic Potentials
Glutamate Receptors
Endocytosis
Glycine
Binding Sites

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Co-induction of LTP and LTD and its regulation by protein kinases and phosphatases. / Grey, Kathryn B.; Burrell, Brian D.

In: Journal of Neurophysiology, Vol. 103, No. 5, 01.05.2010, p. 2737-2746.

Research output: Contribution to journalArticle

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