Neuronal Activity at Synapse Resolution: Reporters and Effectors for Synaptic Neuroscience

Gobbo, Francesco; Cattaneo, Antonino

doi:10.3389/fnmol.2020.572312

Cited by 10 publications

(5 citation statements)

References 226 publications

(329 reference statements)

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“…The next challenge will involve visualising activity‐dependent changes during hippocampal learning at the synaptic resolution [229]. Currently, most studies interrogate activity‐dependent changes at the neuronal level via cell‐wide in vivo calcium imaging or optogenetic manipulation.…”

Section: Perspectivesmentioning

confidence: 99%

Long‐term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses

2021

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Synapses between neurons are malleable biochemical structures, strengthening and diminishing over time dependent on the type of information they receive. This phenomenon known as synaptic plasticity underlies learning and memory, and its different forms, Long-Term Potentiation (LTP) and Long-Term Depression (LTD) perform varied cognitive roles in reinforcement, relearning and associating memories. Moreover, both LTP and LTD can exist in an early transient form (early-LTP/LTD) or a late persistent form (late-LTP/LTD), which are triggered by different induction protocols, and also differ in their dependence on protein synthesis and the involvement of key molecular players. Beyond homosynaptic modifications, synapses can also interact with one another. This is encapsulated in the Synaptic Tagging and Capture hypothesis (STC), where synapses expressing early-LTP/LTD present a 'tag' that can capture the protein synthesis products generated during a temporally proximal late-LTP/LTD induction. This 'tagging' phenomenon forms the framework of synaptic interactions in various conditions, and accounts for the cellular basis of the time-dependent associativity of short-lasting and long-lasting memories. All these synaptic modifications take place under controlled neuronal conditions, regulated by subcellular elements such as epigenetic regulation, proteasomal degradation and neuromodulatory signals. Here, we review current understanding of the different forms of synaptic plasticity and its regulatory mechanisms in the hippocampus, a brain region critical for memory formation. We also discuss expression of plasticity in hippocampal CA2 area, a long-overlooked narrow hippocampal subfield, and the behavioural correlate of STC. Lastly, we put forth perspectives for an integrated view of memory representation in synapses.

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Section: Perspectivesmentioning

confidence: 99%

Long‐term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses

2021

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“…How does the brain remember? This classical question has recently received considerable attention focusing on the central nervous system’s handling of engrams [40, 33, 21, 13, 23]. These involve coordinated synaptic changes, mandating a cell-wide coherent explanation of multisynaptic plasticity.…”

Section: Introductionmentioning

confidence: 99%

Explaining neuroplasticity using equivalent circuits: A mechanistic perspective

Nilsson

2023

Preprint

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This paper introduces a comprehensive mechanistic model of a neuron with plasticity that explains the creation of engrams, the biophysical correlates of memory. In the context of a single neuron, this means clarifying how information conveyed as time-varying input signals is processed, stored, and subsequently recalled. Moreover, the model addresses two additional, long-standing, specific biological problems: how Hebbian plasticity, which amplifies synaptic weight, integrates with homeostatic plasticity, which stabilizes it, and how to identify a concise learning rule for synapses. In this study, a biologically accurate Hodgkin-Huxley-style electric-circuit equivalent is derived through a one-to-one mapping from the known properties of ion channels. The dynamics of the synaptic cleft, which is often overlooked, is found to be essential in this process. Analysis of the model reveals a simple and concise learning rule, indicating that the neuron functions as an internal-feedback adaptive filter, which is commonly used in signal processing. Simulation results confirm the circuit's functionality, stability, and convergence, demonstrating that even a single neuron without external feedback can function as a potent signal processor. The article is interdisciplinary and spans a broad range of subjects within the realm of biophysics, including neurobiology, electronics, and signal processing.

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“…However, certain applications and particular brain functions, for instance, the maintenance of long-term memory in hippocampus, depend on subcomponents of neurons, such as a synaptic compartment or subsets of synapses. Although such subcellular specificity cannot be sufficiently targeted by genetic identity, the specificity can be achieved in combination with precise delivery of light [2][3][4] . Some of the most intensely studied processes in neuroscience are 'when,' 'where,' and 'how' memories are formed, consolidated, retrieved, and their storage maintained.…”

Section: Introductionmentioning

confidence: 99%

A Photoactivated Protein Degrader for Optical Control of Synaptic Function

Jou

Grau‐Perales

et al. 2023

Preprint

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Hundreds of proteins determine the function of synapses, and synapses define the neuronal circuits that subserve myriad brain, cognitive, and behavioral functions. It is thus necessary to precisely manipulate specific proteins at specific sub-cellular locations and times to elucidate the roles of particular proteins and synapses in brain function. We developed PHOtochemically TArgeting Chimeras (PHOTACs) as a strategy to optically degrade specific proteins with high spatial and temporal precision. PHOTACs are small molecules that, upon wavelength-selective illumination, catalyze ubiquitylation and degradation of target proteins through endogenous proteasomes. Here we describe the design and chemical properties of a PHOTAC that targets Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα), which is abundant and crucial for baseline synaptic function of excitatory neurons. We validate the PHOTAC strategy, showing that the CaMKIIα-PHOTAC is effective in mouse brain tissue. Light activation of CaMKIIα-PHOTAC removed CaMKIIα from regions of the mouse hippocampus only within 25 μm of the illuminated brain surface. The optically-controlled degradation decreases synaptic function within minutes of light activation, measured by the light-initiated attenuation of evoked field excitatory postsynaptic potential (fEPSP) responses to physiological stimulation. The PHOTACs methodology should be broadly applicable to other key proteins implicated in synaptic function, especially for evaluating their precise roles in the maintenance of long-term potentiation and memory within subcellular dendritic domains.

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Neuronal Activity at Synapse Resolution: Reporters and Effectors for Synaptic Neuroscience

Cited by 10 publications

References 226 publications

Long‐term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses

Long‐term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses

Explaining neuroplasticity using equivalent circuits: A mechanistic perspective

A Photoactivated Protein Degrader for Optical Control of Synaptic Function

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