Response of Hippocampal Synapses to Natural Stimulation Patterns

Dobrunz, Lynn E.; Stevens, Charles F.

doi:10.1016/s0896-6273(00)80687-x

Cited by 183 publications

(203 citation statements)

References 44 publications

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“…The present study is the first example that targeted manipulation of biochemical signaling in axon terminals can enhance learning and synaptic plasticity in mammals. In addition, our data support the long-standing hypothesis that short-term presynaptic plasticity influences the induction of LTP (Dobrunz and Stevens, 1999). Specifically, our results demonstrate a novel cellular function of H-ras/ERK signaling: by regulating the density of docked vesicles via ERK-dependent phosphorylation of synapsin I, experience-dependent changes in the activity of presynaptic H-ras modulate the induction of longterm synaptic plasticity underlying learning through a frequencydependent facilitation of neurotransmitter release.…”

Section: Discussionsupporting

confidence: 83%

“…Studies using a variety of invertebrate systems have provided compelling evidence for the involvement of presynaptic plasticity in invertebrate learning and memory (Burrell and Sahley, 2001). Additionally, computational models have suggested that shortterm presynaptic plasticity is an important mechanism for cortical processing in mammals (Tsodyks and Markram, 1997;Varela et al, 1997;Dobrunz and Stevens, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Kushner¹,

Elgersma²,

Murphy³

et al. 2005

J. Neurosci.

170

162

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G12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesicles in glutamatergic terminals, an increased frequency of miniature EPSCs, and increased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Kushner¹,

Elgersma²,

Murphy³

et al. 2005

J. Neurosci.

170

162

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“…However, response amplitudes to individual stimuli were similar from trial to trial. Repeated administration of either the sleep or wake stimulus protocol elicited similar responses to each repetition (data not shown), as has been described for analogous experiments using natural activity patterns examining Schaffer collateral synaptic responses (Dobrunz and Stevens, 1999).…”

Section: The Glutamate-glutamine Cycle Dynamically Regulates Ipscs Evsupporting

confidence: 66%

Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1

2006

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Vesicular GABA and intraterminal glutamate concentrations are in equilibrium, suggesting inhibitory efficacy may depend on glutamate availability. Two main intraterminal glutamate sources are uptake by neuronal glutamate transporters and glutamine synthesized through the astrocytic glutamate-glutamine cycle. We examined the involvement of the glutamate-glutamine cycle in modulating GABAergic synaptic efficacy. In the absence of neuronal activity, disruption of the glutamate-glutamine cycle by blockade of neuronal glutamine transport with ␣-(methylamino) isobutyric acid (MeAIB; 5 mM) or inhibition of glutamine synthesis in astrocytes with methionine sulfoximine (MSO; 1.5 mM) had no effect on miniature IPSCs recorded in hippocampal area CA1 pyramidal neurons. However, after a period of moderate synaptic activity, application of MeAIB, MSO, or dihydrokainate (250 M; an astrocytic glutamate transporter inhibitor) significantly reduced evoked IPSC (eIPSC) amplitudes. The MSO effect could be reversed by exogenous application of glutamine (5 mM), whereas glutamine could not rescue the eIPSC decreases induced by the neuronal glutamine transporter inhibitor MeAIB. The activity-dependent reduction in eIPSCs by glutamate-glutamine cycle blockers was accompanied by an enhanced blocking effect of the low-affinity GABA A receptor antagonist, TPMPA [1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid], consistent with diminished GABA release. We further corroborated this hypothesis by examining MeAIB effects on minimal stimulation-evoked quantal IPSCs (meIPSCs). We found that, in MeAIB-containing medium, moderate stimulation induced depression in potency of meIPSCs but no change in release probability, consistent with reduced vesicular GABA content. We conclude that the glutamate-glutamine cycle is a major contributor to synaptic GABA release under physiological conditions, which dynamically regulates inhibitory synaptic strength.

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“…Formation of sharp-wave ripples depends on coordinated firing of CA3 neurons, orchestrated by parvalbumin-expressing fast-spiking interneurons (35). Place cells fire when an animal reaches a specific position in space, and firing of place cells in turn can induce LTP in vitro (32,36,37). How might the changes in short-term and long-term synaptic plasticity that we observe in IM-AA mice alter sharpwave ripples, place cell formation and stability, and ultimately spatial learning and memory?…”

Section: Discussionmentioning

confidence: 99%

Calcium sensor regulation of the Ca _V 2.1 Ca ²⁺ channel contributes to long-term potentiation and spatial learning

Nanou

Scheuer

Catterall

2016

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

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Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca 2+ type 2.1 (Ca V 2.1) channels. However, the contribution of regulation of Ca V 2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of Ca V 2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg 2+ . The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of Ca V 2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.calcium channel | calmodulin | synaptic plasticity | calcium sensor proteins | hippocampus A ctivity-dependent modification of synaptic strength in synapses in the central nervous system is important for hippocampaldependent information processing and for spatial learning and memory (1). Short-term and long-term modifications in synaptic strength are regulated by the frequency and pattern of presynaptic spiking (2-5). Regulation of voltage-gated Ca 2+ channel type 2.1 (Ca V 2.1) by calmodulin (CaM) and related Ca 2+ sensor (CaS) proteins causes Ca 2+ -dependent facilitation and inactivation of P/Qtype Ca 2+ currents (6-12) that results in short-term facilitation and rapid depression of synaptic transmission (9,(12)(13)(14). Deletion of the gene encoding Ca V 2.1 channels (15) or mutation of their CaS protein binding domain (12-14) impairs short-term synaptic plasticity. Although regulation of Ca V 2.1 channels contributes to short-term synaptic plasticity in multiple types of synapses, the functional role of this form of synaptic regulation in learning and memory is unknown.Long-term potentiation (LTP) of synaptic transmission in the hippocampus is thought to be important for spatial learning and memory (16). High-frequency stimuli induce LTP, which depends on postsynaptic Ca 2+ entry via NMDA-specific glutamate rec...

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Response of Hippocampal Synapses to Natural Stimulation Patterns

Cited by 183 publications

References 44 publications

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1

Calcium sensor regulation of the Ca _V 2.1 Ca ²⁺ channel contributes to long-term potentiation and spatial learning

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Response of Hippocampal Synapses to Natural Stimulation Patterns

Cited by 183 publications

References 44 publications

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1

Calcium sensor regulation of the Ca V 2.1 Ca 2+ channel contributes to long-term potentiation and spatial learning

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Calcium sensor regulation of the Ca _V 2.1 Ca ²⁺ channel contributes to long-term potentiation and spatial learning