Impermanence of dendritic spines in live adult CA1 hippocampus

Attardo, Alessio; Fitzgerald, James E.; Schnitzer, Mark J.

doi:10.1038/nature14467

Cited by 339 publications

(364 citation statements)

References 34 publications

(73 reference statements)

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“…Together, these data indicate that experience may serve to bind plastic cells into a background network structure provided by rigid cells. Given recent findings that hippocampal map may not be as stable as once thought (Attardo et al, 2015;Rubin et al, 2015;Ziv et al, 2013), the ability to flexibly add neurons to an existing framework may facilitate, rather than hinder, rapid acquisition of information (Tse et al, 2007), or it may serve as a mechanism allowing for generalization (Xu & Sudhof, 2013).…”

Section: Replay May Reveal the Underlying Hippocampal Circuitrymentioning

confidence: 99%

The content of hippocampal “replay”

2018

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One of the most striking features of the hippocampal network is its ability to self-generate neuronal sequences representing temporally compressed, spatially coherent paths. These brief events, often termed "replay" in the scientific literature, are largely confined to non-exploratory states such as sleep or quiet rest. Early studies examining the content of replay noted a strong correlation between the encoded spatial information and the animal's prior behavior; thus, replay was initially hypothesized to play a role in memory formation and/or systems-level consolidation via "off-line" reactivation of previous experiences. However, recent findings indicate that replay may also serve as a memory retrieval mechanism to guide future behavior or may be an incidental reflection of pre-existing network assemblies. Here, I will review what is known regarding the content of replay events and their correlation with past and future actions, and I will discuss how this knowledge might inform or constrain models which seek to explain the circuit-level mechanisms underlying these events and their role in mnemonic processes.memory, place cells, reactivation, review, ripple | I N TR ODU C TI ONAdaptive behavior requires the brain to preserve coherent representations of experience and later extract that stored information to inform future behaviors. For decades, researchers have utilized goal-directed navigation and the brain's spatial memory system as a specific example to explore more general questions regarding memory processes (Tolman, 1948). Two discoveries in particular have prompted researchers to focus such studies on the hippocampus: (a) Human patients and animal models with damage to their medial temporal lobe (and the hippocampus in particular) display severe impairments in their ability to form new episodic and spatial memories (Morris et al., 1982;Scoville & Milner, 1957;Squire et al., 2004); and (b) individual neurons within the hippocampus represent spatial information in their firing patterns during exploration, implicating the hippocampus in the processing and storage of spatial memories (Moser et al., 2008;O'Keefe and Dostrovsky, 1971). A persistent, fundamental question within this domain is how an entire experience or spatial trajectory, which may be represented within the hippocampus by the activity of tens of thousands of neurons ordered in a precise temporal sequence, can be coherently stored within that neural network or purposefully retrieved at the exact time when the stored information would be useful for guiding future decisions.Among several lines of investigation attempting to address this question (Garner et al., 2012;Josselyn et al., 2015; Ramirez et al., 2013;Tse et al., 2007), hippocampal ripples and ripple-based "replay" have emerged as strong candidate mechanisms which may facilitate both the initial storage and later retrieval of complex, temporally ordered information about experience. Ripples are brief (50-100 ms duration), high-frequency (150-300 Hz) network oscillations within ...

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Section: Replay May Reveal the Underlying Hippocampal Circuitrymentioning

confidence: 99%

The content of hippocampal “replay”

2018

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“…Estradiol enhances excitatory neurotransmission throughout the hippocampus (8)(9)(10), and activates BDNF signaling in the mossy fiber system (11). Dendritic spines turn over more rapidly in the hippocampus than in the neocortex (12), particularly in the case of estradiol-induced spines (13). Such rapid, transient, and apparently indiscriminate increases in excitatory synapse formation would seem, at first sight, to be more likely to interfere with preexisting brain circuits and impair normal information processing than to enhance cognitive function.…”

mentioning

confidence: 99%

Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements

Phan

Suschkov

Molinaro

et al. 2015

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

129

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Dramatic increases in hippocampal spine synapse density are known to occur within minutes of estrogen exposure. Until now, it has been assumed that enhanced spinogenesis increased excitatory input received by the CA1 pyramidal neurons, but how this facilitated learning and memory was unclear. Delivery of 17β-estradiol or an estrogen receptor (ER)-α (but not ER-β) agonist into the dorsal hippocampus rapidly improved general discrimination learning in female mice. The same treatments increased CA1 dendritic spines in hippocampal sections over a time course consistent with the learning acquisition phase. Surprisingly, estrogen-activated spinogenesis was associated with a decrease in CA1 hippocampal excitatory input, rapidly and transiently reducing CA1 AMPA activity via a mechanism likely reflecting AMPA receptor internalization and creation of silent or immature synapses. We propose that estrogens promote hippocampally mediated learning via a mechanism resembling some of the broad features of normal development, an initial overproduction of functionally immature connections being subsequently "pruned" by experience.immature synapse | short-term memory | structural plasticity | synaptic plasticity | signal-to-noise ratio E stradiol rapidly and dramatically increases hippocampal dendritic spine and synapse density within minutes of application (1-4). There is a strong correlative association between estrogeninduced spinogenesis and improvements in cognition (5); however, the relationship of these structural changes to estrogen-induced alterations in hippocampal function is unclear. Our laboratory recently reported that the density of hippocampal CA1 pyramidal dendritic spines increases very rapidly after systemic treatment with 17β-estradiol or estrogen receptor (ER) -selective agonists in ovariectomized female mice, changes that are paralleled by learning enhancements (2, 3). Estrogen-induced rapid structural changes are substantial, increasing spine density by 30-50% within 15-40 min of hormone application (1-3, 6). As a result, adult rodents can experience the addition of thousands of CA1 synapses within a span of minutes after exposure to estradiol. These effects of estrogens reproduce the changes occurring during the 4-d estrous cycle of female rodents, which include the induction of CA1 spines (7).How these processes contribute to the behavioral changes observed after estradiol treatment is not understood. Estradiol enhances excitatory neurotransmission throughout the hippocampus (8-10), and activates BDNF signaling in the mossy fiber system (11). Dendritic spines turn over more rapidly in the hippocampus than in the neocortex (12), particularly in the case of estradiol-induced spines (13). Such rapid, transient, and apparently indiscriminate increases in excitatory synapse formation would seem, at first sight, to be more likely to interfere with preexisting brain circuits and impair normal information processing than to enhance cognitive function.How then, does enhancement of spine formation lead to improved ...

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“…3(b)], which can be mistaken for classical spines if the optical resolution is insufficient. 14,48 A striking example is shown in Figs. 3(c) and 3(d): a protrusion is resolved by STED microscopy into an unusual form of a fork-like structure with three sub-branches [ Fig. 3(c)], but it looks like a spine of the mushroom type at confocal resolution [ Fig.…”

Section: Imaging Of Dendritic Spinesmentioning

confidence: 98%

Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation

et al. 2016

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Abstract. Emerging all-optical methods provide unique possibilities for noninvasive studies of physiological processes at the cellular and subcellular scale. On the one hand, superresolution microscopy enables observation of living samples with nanometer resolution. On the other hand, light can be used to stimulate cells due to the advent of optogenetics and photolyzable neurotransmitters. To exploit the full potential of optical stimulation, light must be delivered to specific cells or even parts of cells such as dendritic spines. This can be achieved with computer generated holography (CGH), which shapes light to arbitrary patterns by phase-only modulation. We demonstrate here in detail how CGH can be incorporated into a stimulated emission depletion (STED) microscope for photostimulation of neurons and monitoring of nanoscale morphological changes. We implement an original optical system to allow simultaneous holographic photostimulation and superresolution STED imaging. We present how synapses can be clearly visualized in live cells using membrane stains either with lipophilic organic dyes or with fluorescent proteins. We demonstrate the capabilities of this microscope to precisely monitor morphological changes of dendritic spines after stimulation. These all-optical methods for cell stimulation and monitoring are expected to spread to various fields of biological research in neuroscience and beyond. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Impermanence of dendritic spines in live adult CA1 hippocampus

Cited by 339 publications

References 34 publications

The content of hippocampal “replay”

The content of hippocampal “replay”

Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements

Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation

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