Mediation of Hippocampal Mossy Fiber Long-Term Potentiation by Cyclic AMP

Weisskopf, Marc G.; Castillo, Pablo E.; Zalutsky, Robert A.; Nicoll, Roger A.

doi:10.1126/science.7916482

Cited by 559 publications

(483 citation statements)

References 56 publications

Supporting

Mentioning

445

Contrasting

Unclassified

Order By: Relevance

“…In contrast, in stratum lucidum interneurons HFS induces synaptic depression rather than potentiation [50,67]. Likewise, activation of the cAMP pathway by forskolin leads to a large chemical potentiation at mossy fiber-CA3 pyramidal neuron synapses [45,82], but has only minimal effects on monosynaptic transmission at mossy fiber-stratum lucidum interneurons [55]. As synaptic plasticity at mossy fiber synapses is believed to be expressed presynaptically [64], these results suggest that the release properties of filopodial extensions and small boutons in the CA3 region differ substantially from those of large mossy fiber boutons.…”

Section: Differential Synaptic Transmission At Mossy Fiber-pyramidal mentioning

confidence: 99%

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Bischofberger

Engel

Frotscher

et al. 2006

Pflugers Arch - Eur J Physiol

110

View full text Add to dashboard Cite

It is widely accepted that the hippocampus plays a major role in learning and memory. The mossy fiber synapse between granule cells in the dentate gyrus and pyramidal neurons in the CA3 region is a key component of the hippocampal trisynaptic circuit. Recent work, partially based on direct presynaptic patch-clamp recordings from hippocampal mossy fiber boutons, sheds light on the mechanisms of synaptic transmission and plasticity at mossy fiber synapses. A high Na + channel density in mossy fiber boutons leads to a large amplitude of the presynaptic action potential. Together with the fast gating of presynaptic Ca 2+ channels, this generates a large and brief presynaptic Ca 2+ influx, which can trigger transmitter release with high efficiency and temporal precision. The large number of release sites, the large size of the releasable pool of vesicles, and the huge extent of presynaptic plasticity confer unique strength to this synapse, suggesting a large impact onto the CA3 pyramidal cell network under specific behavioral conditions. The characteristic properties of the hippocampal mossy fiber synapse may be important for pattern separation and information storage in the dentate gyrus-CA3 cell network.Keywords Presynaptic recording . Mossy fiber boutons . Mossy fiber synapses . Hippocampus . Autoassociative networks . Episodic memory . Synaptic efficacyThe mossy fiber synapse: a key connection in the hippocampal networkThe hippocampal formation consists of three types of principal neurons: granule cells in the dentate gyrus, CA3 pyramidal cells, and CA1 pyramidal neurons. These cells are interconnected by glutamatergic synapses, forming the classical trisynaptic circuit (Fig. 1a,b). Dentate gyrus granule cells receive excitatory glutamatergic input from layer 2 pyramidal cells of the entorhinal cortex and project to CA3 pyramidal cells. CA3 pyramidal cells project to CA1 cells, which in turn project to the subiculum and back to the entorhinal cortex [4]. In addition to this trisynaptic circuit, there is also a direct input from the entorhinal cortex to both CA3 and CA1 pyramidal cells. Furthermore, CA3 pyramidal neurons are extensively connected to each other via recurrent collateral synapses.The nonmyelinated axons of the granule cells, the socalled mossy fibers, show several structural properties that distinguish them from the other synaptic pathways [39]. They project to the CA3 region, mainly traveling within a narrow band termed "stratum lucidum." Several (∼15) large "giant" boutons (∼3-5-μm diameter) emerge from a single mossy fiber axon, either arranged in an en passant manner or attached to the main axon via a short perpendicular axonal branch [1,8,29,31] (Fig. 1c,d). A large mossy fiber bouton typically contacts only a single CA3 pyramidal neuron [21], and a mossy fiber axon contacts a given CA3 pyramidal neuron only once, as boutons are ∼150 μm apart. As the rat hippocampus contains ∼1 million granule cells

show abstract

Section: Differential Synaptic Transmission At Mossy Fiber-pyramidal mentioning

confidence: 99%

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Bischofberger

Engel

Frotscher

et al. 2006

Pflugers Arch - Eur J Physiol

110

View full text Add to dashboard Cite

show abstract

“…Using methods of conventional EPSC measurements, synaptosome measurements, and optical quantal analysis, previous studies have implicated cAMP formation with increased vesicle availability rather than or in addition to vesicle release probability. However, most previous studies have not clearly distinguished vesicle availability at existing, active synapses versus activation of previously inactive synapses (Huang et al, 1994;Weisskopf et al, 1994;Tong et al, 1996;Bolshakov et al, 1997;Lonart et al, 1998;Kaneko and Takahashi, 2004;Reid et al, 2004;Menegon et al, 2006) (but see Ma et al, 1999;Kohara et al, 2001). Furthermore, some studies have explicitly excluded an effect of cAMP signaling on the number of active synapses (Trudeau et al, 1996).…”

Section: Camp and Presynaptic Potentiationmentioning

confidence: 99%

“…Previous evidence has implicated the cAMP pathway in various forms of increased presynaptic efficacy, specifically the activation status of synaptic vesicles (Huang et al, 1994;Weisskopf et al, 1994;Tong et al, 1996;Ma et al, 1999;Kohara et al, 2001). We therefore explored the hypothesis that cAMP signaling participates in setting the baseline percentage of presynaptically active synapses and in recovery from adaptation to strong depolarization.…”

Section: Introductionmentioning

confidence: 99%

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Moulder¹,

Jiang²,

Chang³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

Glutamate generates fast postsynaptic depolarization throughout the CNS. The positive-feedback nature of glutamate signaling likely necessitates flexible adaptive mechanisms that help prevent runaway excitation. We have previously explored presynaptic adaptive silencing, a form of synaptic plasticity produced by ongoing neuronal activity and by strong depolarization. Unsilencing mechanisms that maintain active synapses and restore normal function after adaptation are also important, but mechanisms underlying such presynaptic reactivation remain unexplored. Here we investigate the involvement of the cAMP pathway in the basal balance between silenced and active synapses, as well as the recovery of baseline function after depolarization-induced presynaptic silencing. Activation of the cAMP pathway activates synapses that are silent at rest, and pharmacological inhibition of cAMP signaling silences basally active synapses. Adenylyl cyclase (AC) 1 and AC8, the major Ca 2ϩ -sensitive AC isoforms, are not crucial for the baseline balance between silent and active synapses. In cells from mice doubly deficient in AC1 and AC8, the baseline percentage of active synapses was only modestly reduced compared with wild-type synapses, and forskolin unsilencing was similar in the two genotypes. Nevertheless, after strong presynaptic silencing, recovery of normal function was strongly inhibited in AC1/AC8-deficient synapses. The entire recovery phenotype of the double null was reproduced in AC8-deficient but not AC1-deficient cells. We conclude that, under normal conditions, redundant cyclase activity maintains the balance between presynaptically silent and active synapses, but AC8 plays a particularly important role in rapidly resetting the balance of active to silent synapses after adaptation to strong activity.

show abstract

“…The rate of decline of the NMDA-dependent EPSCs (excitatory post synaptic currents) depends on the Pr, because a higher Pr results in a higher number of NMDA receptors being opened per stimulus. Although mossy fiber LTP is NMDA receptor independent, Weisskopf and Nicoll 36 showed that NMDA receptors are present at mossy fiber synapses and used the MK-801 method to reveal that upon LTP induction, there is a large increase in the probability of release, 37 emphasizing the presynaptic expression of that type of LTP. Although most of the studies were performed in slices, the presynaptic nature of mossy fiber LTP has been also shown in cultured granule cells.…”

Section: Presynaptic Ltp Independent Of Nmda Receptormentioning

confidence: 99%

“…64 Several proteins of the synaptic vesicle cycle are substrates for PKA and their relevant significance in long-term plasticity will be discussed below. A number of studies have evidenced the role of that biochemical cascade in mossy fiber LTP (Huang et al, 32 Weisskopf et al, 37 and Huang and Kandel, 65 but see also Kamiya et al, 66 ). Different types of presynaptic glutamate receptors have an important role in presynaptic mossy fiber LTP [67][68][69] and recent excellent reviews have discussed that issue in detail.…”

Section: Presynaptic Ltp Independent Of Nmda Receptormentioning

confidence: 99%

Active zones for presynaptic plasticity in the brain

García-Junco-Clemente

Linares-Clemente

Fernández‐Chacón

2005

Mol Psychiatry

View full text Add to dashboard Cite

Some of the most abundant synapses in the brain such as the synapses formed by the hippocampal mossy fibers, cerebellar parallel fibers and several types of cortical afferents express presynaptic forms of long-term potentiation (LTP), a putative cellular model for spatial, motor and fear learning. Those synapses often display presynaptic mechanisms of LTP induction, which are either NMDA receptor independent of dependent of presynaptic NMDA receptors. Recent investigations on the molecular mechanisms of neurotransmitter release modulation in short-and long-term synaptic plasticity in central synapses give a preponderant role to active zone proteins as Munc-13 and RIM1-alpha, and point toward the maturation process of synaptic vesicles prior to Ca 2 þ -dependent fusion as a key regulatory step of presynaptic plasticity.

show abstract

Mediation of Hippocampal Mossy Fiber Long-Term Potentiation by Cyclic AMP

Cited by 559 publications

References 56 publications

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Active zones for presynaptic plasticity in the brain

Contact Info

Product

Resources

About

Mediation of Hippocampal Mossy Fiber Long-Term Potentiation by Cyclic AMP

Cited by 559 publications

References 56 publications

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Active zones for presynaptic plasticity in the brain

Contact Info

Product

Resources

About

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing