The fate of hippocampal synapses depends on the sequence of plasticity-inducing events

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.

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The fate of hippocampal synapses depends on the sequence of plasticity-inducing events

eLife ◽

10.7554/elife.39151 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 10

Author(s):

J Simon Wiegert ◽

Mauro Pulin ◽

Christine Elizabeth Gee ◽

Thomas G Oertner

Keyword(s):

Hippocampal Slice ◽

Specific Activity ◽

Activity Patterns ◽

Long Term Potentiation ◽

Information Storage ◽

Two Photon ◽

Term Potentiation ◽

Hippocampal Synapses ◽

Activity Dependent

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.

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Novel Scenes Improve Recollection and Recall of Words

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2008.20086 ◽

2008 ◽

Vol 20 (7) ◽

pp. 1250-1265 ◽

Cited By ~ 38

Author(s):

Daniela B. Fenker ◽

Julietta U. Frey ◽

Hartmut Schuetze ◽

Dorothee Heipertz ◽

Hans-Jochen Heinze ◽

...

Keyword(s):

Specific Activity ◽

Activity Patterns ◽

Long Term Potentiation ◽

Contextual Memory ◽

Memory Enhancement ◽

Term Potentiation ◽

Outdoor Scenes ◽

Indoor And Outdoor ◽

Hippocampus Dependent Memory

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.

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

10.1101/460568 ◽

2018 ◽

Author(s):

Gaurang Mahajan ◽

Suhita Nadkarni

Keyword(s):

Dendritic Spines ◽

Activity Patterns ◽

Long Term Potentiation ◽

Multiple Time Scales ◽

Calcium Stores ◽

Multiple Time ◽

Additional Layer ◽

Term Potentiation ◽

Activity Dependent

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.

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Persistent Synaptic Activity Produces Long-Lasting Enhancement of Endocannabinoid Modulation and Alters Long-Term Synaptic Plasticity

Journal of Neurophysiology ◽

10.1152/jn.01228.2006 ◽

2007 ◽

Vol 97 (6) ◽

pp. 4386-4389 ◽

Cited By ~ 41

Author(s):

Ping Jun Zhu ◽

David M. Lovinger

Keyword(s):

Low Frequency ◽

Long Term Potentiation ◽

Information Storage ◽

Synaptic Activity ◽

Inhibitory Synapses ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Gabaergic Synapses ◽

Activity Dependent

Learning and memory are thought to involve activity-dependent changes in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). Recent studies have indicated that endocannabinoid-dependent modulation of inhibitory transmission facilitates induction of hippocampal LTP and that endocannabinoids play a key role in certain forms of LTD. Here, we show that repetitive low-frequency synaptic stimulation (LFS) produces persistent up-regulation of endocannabinoid signaling at hippocampal CA1 GABAergic synapses. This LFS also produces LTD of inhibitory synapses and facilitates LTP at excitatory, glutamatergic synapses. These endocannabinoid-mediated plastic changes could contribute to information storage within the brain.

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An Endogenous RNA Transcript Antisense to CNGα1 Cation Channel mRNA

Molecular Biology of the Cell ◽

10.1091/mbc.e02-03-0127 ◽

2002 ◽

Vol 13 (10) ◽

pp. 3696-3705 ◽

Cited By ~ 6

Author(s):

Chin-Hung Cheng ◽

David Tai-Wai Yew ◽

Hiu-Yee Kwan ◽

Qing Zhou ◽

Yu Huang ◽

...

Keyword(s):

Expression System ◽

Expression Patterns ◽

Long Term Potentiation ◽

Information Storage ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Oocyte Expression System ◽

Neuronal Functions ◽

Rna Transcript

CNG channels are cyclic nucleotide-gated Ca2+-permeable channels that are suggested to be involved in the activity-dependent alterations of synaptic strength that are thought to underlie information storage in the CNS. In this study, we isolated an endogenous RNA transcript antisense to CNGα1 mRNA. This transcript was capable of down-regulating the expression of sense CNGα1 in theXenopus oocyte expression system. RT-PCR, Northern blot, and in situ hybridization analyses showed that the transcript was coexpressed with CNGα1 mRNA in many regions of human brain, notably in those regions that were involved in long-term potentiation and long-term depression, such as hippocampal CA1 and CA3, dentate gyrus, and cerebellar Purkinje layer. Comparison of expression patterns between adult and fetal cerebral cortex revealed that there were concurrent developmental changes in the expression levels of anti-CNG1 and CNGα1. Treatment of human glioma cell T98 with thyroid hormone T3 caused a significant increase in anti-CNG1 expression and a parallel decrease in sense CNGα1 expression. These data suggest that the suppression of CNGα1 expression by anti-CNG1 may play an important role in neuronal functions, especially in synaptic plasticity and cortical development. Endogenous antisense RNA-mediated regulation may represent a new mechanism through which the activity of ion channels can be regulated in the human CNS.

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Photolytic release of nitric oxide modulates NMDA receptor-mediated transmission but does not induce long-term potentiation at hippocampal synapses

Neuropharmacology ◽

10.1016/0028-3908(94)90039-6 ◽

1994 ◽

Vol 33 (11) ◽

pp. 1375-1385 ◽

Cited By ~ 57

Author(s):

K.P.S.J. Murphy ◽

J.H. Williams ◽

N. Bettache ◽

T.V.P. Bliss

Keyword(s):

Nitric Oxide ◽

Nmda Receptor ◽

Long Term Potentiation ◽

Term Potentiation ◽

Hippocampal Synapses

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The Vertical Lobe of Cephalopods

The Oxford Handbook of Invertebrate Neurobiology ◽

10.1093/oxfordhb/9780190456757.013.29 ◽

2017 ◽

pp. 558-574 ◽

Cited By ~ 1

Author(s):

Ana Turchetti-Maia ◽

Tal Shomrat ◽

Binyamin Hochner

Keyword(s):

Complex Networks ◽

Long Term Potentiation ◽

Learning Networks ◽

Neuronal Circuitry ◽

Cellular Processes ◽

Term Potentiation ◽

Matrix Organization ◽

Activity Dependent ◽

Similar Organization

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.

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