Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol

Kemp, Nicola; McQueen, Jane; Faulkes, Suzanna; Bashir, Zafar I.

doi:10.1046/j.1460-9568.2000.00903.x

Cited by 189 publications

(156 citation statements)

References 35 publications

(47 reference statements)

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“…Although several groups have shown that PKC activity is necessary for mGluR LTD in several brain regions, including CA1 (3,15), it was also demonstrated that high-frequencyinduced PKC activation inhibited synaptically induced mGluR LTD in the dentate gyrus (16,17), demonstrating the dependence of mGluR LTD metaplasticity on PKC. The location of mGluR LTD activation and maintenance has also been the subject of debate with some studies implicating a presynaptic expression mechanism and others implicating a postsynaptic one (5,13,21). To study the dynamics and location of this possible interaction, it was necessary to isolate the effects of m1-mediated signaling on the response to stimulating mGluRs by removing m1 receptors.…”

Section: Discussionmentioning

confidence: 99%

Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus

Kamsler

McHugh

Gerber

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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To investigate the role of M1 muscarininc acetylcholine receptors (m1 receptors) in metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD), we produced mouse lines in which deletion of the m1 gene is restricted to the forebrain (FB-m1KO) or hippocampal CA3 pyramidal neurons (CA3-m1KO). Stimulation in FB-m1KO hippocampal slices resulted in excitatory postsynaptic potentials and long-term synaptic plasticity (long-term potentiation and LTD) similar to controls. The mice were deficient in (S)-3,5-dihydroxyphenylglycine hydrate (DHPG)-induced mGluR LTD, which correlated with a presynaptic increase in the release of neurotransmitters. Protein kinase C (PKC) activity, which is downstream from both mGluRs and m1 receptors, was reduced in CA3 but not in CA1. The presynaptic requirement of m1 receptors was confirmed by the lack of DHPG-induced mGluR LTD in the CA1 of slices from CA3-m1KO mice. mGluR LTD was rescued by stimulating PKC activity pharmacologically in CA3-m1KO mice. These data confirm a role for PKC activation in presynaptic induction of mGluR LTD and distinguish between the roles of mGluRs and m1 receptors. M 1 muscarinic acetylcholine receptors (m1 receptors) and group I metabotropic glutamate receptors (mGluRs) are expressed in hippocampal pyramidal neurons, activate protein kinase C (PKC) via a "q" type G protein (Gq)-coupled cascade (1-3), and have been implicated in inducing and modulating plasticity in CA3-CA1 synapses. The nature of the interaction between these two overlapping signal pathways is unknown. Although ionotropic N-methyl-d-aspartate (NMDA) receptors have been most prominently implicated in the phenomena of long-term potentiation (LTP) and long-term depression (LTD), changes in synaptic efficacy can also be mediated by metabotropic-receptor-mediated processes. G-protein-coupled receptors (such as m1 receptors and mGluRs) can change synaptic efficacy when stimulated and can also act as neuromodulators by changing synaptic responses to other parallel stimuli (1).Stimulating mGluRs by perfusing the agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) causes a long-lasting decrease in synaptic efficacy (mGluR LTD) (4-6). Similarly, muscarinic agonists also produce transient or long-lasting depression in synaptic efficacy (6, 7). These muscarinic effects vary with the concentration of the agonists used and may be the result of the simultaneous activation of different kinds of muscarinic receptors at distinct synaptic locations (8). It is still not clear which cholinergic receptors mediate cholinergic LTD and whether they act presynaptically or postsynaptically. It is also not clear what the relationship is between mGluR LTD and cholinergic LTD. Recently, Volk et al. (6) have shown that mGluR LTD can be blocked by applying a muscarinic antagonist and that LTD produced by a muscarinic agonist occludes mGluR LTD. They concluded that mGluR LTD and muscarinic LTD are the same process and that mGluRs are required for LTD only when m1 muscarinic receptors are blocked.The mechani...

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Section: Discussionmentioning

confidence: 99%

Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus

Kamsler

McHugh

Gerber

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Some studies suggest that mGluR-LTD is only observed at early developmental time periods in area CA1 (P7-P11) (Bolshakov and Siegelbaum, 1994;Overstreet et al, 1997). However, others indicate that mGluR-LTD is restricted to adult animals (Kemp et al, 2000). There is general agreement that mGluR-LTD is induced postsynaptically (Bolshakov and Siegelbaum, 1994;Oliet et al, 1997;Watabe et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Developmental Switch in Synaptic Mechanisms of Hippocampal Metabotropic Glutamate Receptor-Dependent Long-Term Depression

Nosyreva¹,

Huber²

2005

J. Neurosci.

159

160

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“…To examine whether caveolin-1 is required for mGluR-independent forms of LTD, we examined NMDAR-LTD at CA1 synapses of Cav1 −/− mice. We delivered low-frequency stimulation (LFS; 1,200 pulses at 1 Hz) to Schaffer collateral axons and recorded fEPSCs in area CA1 (35)(36)(37). LFS induced robust depression of fEPSPs in slices from both WT and Cav1 −/− mice, as assessed 35-40 min after stimulation (WT depression to 83 ± 5% of baseline, n = 9; Cav1 −/− depression to 79 ± 4% of baseline, n = 8; P > 0.05 Cav1 −/− vs. WT, P < 0.001 Cav1 −/− or WT vs. baseline; Fig.…”

mentioning

confidence: 99%

Caveolin-1 knockout mice exhibit impaired induction of mGluR-dependent long-term depression at CA3-CA1 synapses

Takayasu

Takeuchi

Kumari

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Group I metabotropic glutamate receptors (mGluR1/5) are important to synaptic circuitry formation during development and to forms of activity-dependent synaptic plasticity. Dysregulation of mGluR1/5 signaling is implicated in some disorders of neurodevelopment, including fragile X syndrome, the most common inherited form of intellectual disabilities and leading cause of autism. Site(s) in the intracellular loops of mGluR1/5 directly bind caveolin-1, an adaptor protein that associates with membrane rafts. Caveolin-1 is the main coat component of caveolae and organizes macromolecular signaling complexes with effector proteins and membrane receptors. We report that long-term depression (LTD) elicited by a single application of the group I mGluR selective agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was markedly attenuated at Schaffer collateral-CA1 synapses of mice lacking caveolin-1 (Cav1 −/− ), as assessed by field recording. In contrast, multiple applications of DHPG produced LTD comparable to that in WT mice. Passive membrane properties, basal glutamatergic transmission and NMDA receptor (NMDAR)-dependent LTD were unaltered. The remaining LTD was reduced by anisomycin, an inhibitor of protein synthesis, by U0126, an inhibitor of MEK1/2 kinases, and by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suggesting mediation by the same mechanisms as in WT. mGluR1/5-dependent activation (phosphorylation) of MEK and extracellular signal-regulated kinase (ERK1/2) was altered in Cav1 −/− mice; basal phosphorylation was increased, but a single application of DHPG had no further effect, and after DHPG, phosphorylation was similar in WT and Cav1 −/− mice. Taken together, our findings suggest that caveolin-1 is required for normal coupling of mGluR1/5 to downstream signaling cascades and induction of mGluR-LTD.G roup I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, are G protein-coupled receptors enriched at excitatory synapses throughout the brain, where they regulate neuronal excitation (1, 2). mGluR1/5s play an important role in the establishment of synaptic circuitry during brain development (3, 4) and in activity-dependent forms of synaptic plasticity, including long-term potentiation and long-term depression as occur in associative learning (5-8). Dysregulated mGluR1/5 signaling is implicated in neurological, psychiatric, and cognitive disorders (8), including fragile X syndrome, the most common inherited cause of intellectual disabilities (9, 10). The broad spectrum of physiological and pathological functions in which mGluRs participate is related to their capacity to initiate diverse signaling events by G protein-dependent and -independent mechanisms (11,12).Membrane rafts (13, 14) and caveolae (15) are specialized membrane domains of the plasma membrane, enriched in cholesterol and glycosphingolipids, that serve as platforms to compartmentalize specific signaling activities at the cell surface. Caveolin-1 is an adaptor protein that interacts with an array of receptors, including m...

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Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol

Cited by 189 publications

References 35 publications

Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus

Presynaptic m1 muscarinic receptors are necessary for mGluR long-term depression in the hippocampus

Developmental Switch in Synaptic Mechanisms of Hippocampal Metabotropic Glutamate Receptor-Dependent Long-Term Depression

Caveolin-1 knockout mice exhibit impaired induction of mGluR-dependent long-term depression at CA3-CA1 synapses

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