scholarly journals Intracellular calcium stores mediate a synapse-specific form of metaplasticity at hippocampal dendritic spines

2018 ◽  
Author(s):  
Gaurang Mahajan ◽  
Suhita Nadkarni

ABSTRACTLong-term plasticity mediated by NMDA receptors supports input-specific, Hebbian forms of learning at excitatory CA3-CA1 connections in the hippocampus. An additional layer of stabilizing mechanisms that act globally as well as locally over multiple time scales may be in place to ensure that plasticity occurs in a constrained manner. Here, we investigate the potential role of calcium (Ca2+) stores associated with the endoplasmic reticulum (ER) in the local regulation of plasticity dynamics at individual CA1 synapses. Our study is spurred by (1) the curious observation that ER is sparsely distributed in dendritic spines, but over-represented in large spines that are likely to have undergone activity-dependent strengthening, and (2) evidence suggesting that ER motility within synapses can be rapid, and accompany activity-regulated spine remodeling. Based on a physiologically realistic computational model for ER-bearing CA1 spines, we characterize the contribution of IP3-sensitive Ca2+ stores to spine Ca2+ dynamics during activity patterns mimicking the induction of long-term potentiation (LTP) and depression (LTD). Our results suggest graded modulation of the NMDA receptor-dependent plasticity profile by ER, which selectively enhances LTD induction. We propose that spine ER can locally tune Ca2+-based plasticity on an as-needed basis, providing a braking mechanism to mitigate runaway strengthening at potentiated synapses. Our model suggests that the presence of ER in the CA1 spine may promote re-use of synapses with saturated strengths.

2018 ◽  
Author(s):  
J. Simon Wiegert ◽  
Mauro Pulin ◽  
Christine E. Gee ◽  
Thomas G. Oertner

AbstractSynapses change their strength in response to specific activity patterns. This functional plasticity is assumed to be the brain’s primary mechanism for information storage. We used optogenetic stimulation of rat hippocampal slice cultures to induce long-term potentiation (LTP), long-term depression (LTD), or both forms of plasticity in sequence. Two-photon imaging of spine calcium signals allowed us to identify stimulated synapses and to follow their fate for the next 7 days. We found that plasticity-inducing protocols affected the synapse’s chance for survival: LTP increased synaptic stability, LTD destabilized synapses, and the effect of the last stimulation protocol was dominant over earlier stimulations. Interestingly, most potentiated synapses were resistant to depression-inducing protocols delivered 24 hours later. Our findings suggest that activity-dependent changes in the transmission strength of individual synapses are transient, but have long-lasting consequences for synaptic lifetime.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
J Simon Wiegert ◽  
Mauro Pulin ◽  
Christine Elizabeth Gee ◽  
Thomas G Oertner

Synapses change their strength in response to specific activity patterns. This functional plasticity is assumed to be the brain’s primary mechanism for information storage. We used optogenetic stimulation of rat hippocampal slice cultures to induce long-term potentiation (LTP), long-term depression (LTD), or both forms of plasticity in sequence. Two-photon imaging of spine calcium signals allowed us to identify stimulated synapses and to follow their fate for the next 7 days. We found that plasticity-inducing protocols affected the synapse’s chance for survival: LTP increased synaptic stability, LTD destabilized synapses, and the effect of the last stimulation protocol was dominant over earlier stimulations. Interestingly, most potentiated synapses were resistant to depression-inducing protocols delivered 24 hr later. Our findings suggest that activity-dependent changes in the transmission strength of individual synapses are transient, but have long-lasting consequences for synaptic lifetime.


PLoS ONE ◽  
2009 ◽  
Vol 4 (6) ◽  
pp. e6021 ◽  
Author(s):  
Amadou T. Corera ◽  
Guy Doucet ◽  
Edward A. Fon

Author(s):  
Ana Turchetti-Maia ◽  
Tal Shomrat ◽  
Binyamin Hochner

We show that the cephalopod vertical lobe (VL) is a promising system for assessing the function and organization of the neuronal circuitry mediating complex learning and memory behavior. Studies in octopus and cuttlefish VL networks suggest an independent evolutionary convergence into a matrix organization of a divergence-convergence (“fan-out fan-in”) network with activity-dependent long-term plasticity mechanisms. These studies also show, however, that the properties of the neurons, neurotransmitters, neuromodulators, and mechanisms of induction and maintenance of long-term potentiation are different from those evolved in vertebrates and other invertebrates, and even highly variable among these two cephalopod species. This suggests that complex networks may have evolved independently multiple times and that, even though memory and learning networks share similar organization and cellular processes, there are many molecular ways of constructing them.


2008 ◽  
Vol 20 (7) ◽  
pp. 1250-1265 ◽  
Author(s):  
Daniela B. Fenker ◽  
Julietta U. Frey ◽  
Hartmut Schuetze ◽  
Dorothee Heipertz ◽  
Hans-Jochen Heinze ◽  
...  

Exploring a novel environment can facilitate subsequent hippocampal long-term potentiation in animals. We report a related behavioral enhancement in humans. In two separate experiments, recollection and free recall, both measures of hippocampus-dependent memory formation, were enhanced for words studied after a 5-min exposure to unrelated novel as opposed to familiar images depicting indoor and outdoor scenes. With functional magnetic resonance imaging, the enhancement was predicted by specific activity patterns observed during novelty exposure in parahippocampal and dorsal prefrontal cortices, regions which are known to be linked to attentional orienting to novel stimuli and perceptual processing of scenes. Novelty was also associated with activation of the substantia nigra/ventral tegmental area of the midbrain and the hippocampus, but these activations did not correlate with contextual memory enhancement. These findings indicate remarkable parallels between contextual memory enhancement in humans and existing evidence regarding contextually enhanced hippocampal plasticity in animals. They provide specific behavioral clues to enhancing hippocampus-dependent memory in humans.


2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.


1993 ◽  
Vol 70 (2) ◽  
pp. 602-609 ◽  
Author(s):  
S. Matsuura ◽  
K. Hirayama ◽  
R. Murata

1. A quantitative analysis of facilitation during the kindling stimulation to the amygdala was conducted by measuring the area between the excitatory potential and the baseline in the averaged tetanic response recorded at the entorhinal cortex. The changes in facilitation were then compared with the development of electrographic afterdischarges (AD) and behavioral seizures in response to successive kindling stimulations. 2. Kindling train pulses (n = 99 or 100; duration: 0.5 ms; frequency: 10 Hz; intensity: AD threshold) were applied to conscious rats until at least one generalized seizure occurred or until 13 stimuli were delivered. 3. Facilitation of the entorhinal responses by kindling stimulation first occurred in the monosynaptic excitatory component and was then followed by a progressive increase in the polysynaptic component that was manifested as the later negative peaks. A clear progressive enhancement was observed in the facilitation by successive kindling stimulations, which also induced prolongation of the AD duration and progression of the seizure stages, indicating that activity-dependent enhancement of facilitation (EF) occurred during the progression of kindling epilepsy. 4. Quantitative analysis revealed that the EF that occurred with the progression of seizure stages was statistically significant (P < 0.001, Friedman test). The AD duration (r = 0.89) and the long-term potentiation (r = 0.85) of the entorhinal responses by single test amygdala stimuli showed a very good linear relation to the EF.(ABSTRACT TRUNCATED AT 250 WORDS)


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