Long-Term Potentiation Induced by θ Frequency Stimulation Is Regulated by a Protein Phosphatase-1-Operated Gate

Autor: Robert D. Blitzer, John H. Connor, George P. Brown, Shirish Shenolikar, Emmanuel M. Landau, Tony Wong, Ravi Iyengar
Rok vydání: 2000
Předmět:
Male
Agonist
medicine.medical_specialty
medicine.drug_class
Long-Term Potentiation
8-Bromo Cyclic Adenosine Monophosphate
Action Potentials
Stimulation
In Vitro Techniques
Biology
Hippocampus
Synaptic Transmission
Rats
Sprague-Dawley
Postsynaptic potential
Protein Phosphatase 1
Internal medicine
Ca2+/calmodulin-dependent protein kinase
Cyclic AMP
Phosphoprotein Phosphatases
medicine
Animals
Receptors
AMPA
ARTICLE
Theta Rhythm
Protein kinase A
Neuronal Plasticity
musculoskeletal
neural
and ocular physiology
General Neuroscience
Excitatory Postsynaptic Potentials
Proteins
Protein phosphatase 1
Long-term potentiation
Adrenergic beta-Agonists
Electric Stimulation
Rats
Cell biology
Endocrinology
nervous system
Calcium-Calmodulin-Dependent Protein Kinases
cAMP-dependent pathway
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Excitatory Amino Acid Antagonists
Ion Channel Gating
Signal Transduction
Zdroj: The Journal of Neuroscience. 20:7880-7887
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.20-21-07880.2000
Popis: Long-term potentiation (LTP) can be induced in the Schaffer collateral→CA1 synapse of hippocampus by stimulation in the θ frequency range (5–12 Hz), an effect that depends on activation of the cAMP pathway. We investigated the mechanisms of the cAMP contribution to this form of LTP in the rat hippocampal slice preparation. θ pulse stimulation (TPS; 150 stimuli at 10 Hz) by itself did not induce LTP, but the addition of either the β-adrenergic agonist isoproterenol or the cAMP analog 8-bromo-cAMP (8-Br-cAMP) enabled TPS-induced LTP. The isoproterenol effect was blocked by postsynaptic inhibition of cAMP-dependent protein kinase. Several lines of evidence indicated that cAMP enabled LTP by blocking postsynaptic protein phosphatase-1 (PP1). Activators of the cAMP pathway reduced PP1 activity in the CA1 region and increased the active form of inhibitor-1, an endogenous inhibitor of PP1. Postsynaptic injection of activated inhibitor-1 mimicked the LTP-enabling effect of cAMP pathway stimulation. TPS evoked complex spiking when isoproterenol was present. However, complex spiking was not sufficient to enable TPS-induced LTP, which additionally required the inhibition of postsynaptic PP1. PP1 inhibition seems to promote the activation of Ca2+/calmodulin-dependent protein kinase (CaMKII), because (1) a CaMKII inhibitor blocked the induction of LTP by TPS paired with either isoproterenol or activated inhibitor-1 and (2) CaMKII in area CA1 was activated by the combination of TPS and 8-Br-cAMP but not by either stimulus alone. These results indicate that the cAMP pathway enables TPS-induced LTP by inhibiting PP1, thereby enhancing Ca2+-independent CaMKII activity.
Databáze: OpenAIRE
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