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ref: -2020 tags: bessel imaging NaJi synapses SPIE date: 11-11-2022 20:14 gmt revision:0 [head]

High-contrast volumetric imaging of synapses and microcirculations with Bessel-droplet two-photon fluorescence microscopy

  • They interferometrically scan the optimized Bessel droplets along the axial dimension to image synapses volumetrically.
  • "Here, we describe axially extended Bessel-droplet foci with suppressed side rings and more resistance to optical aberrations"

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ref: -2020 tags: excitatory inhibitory balance E-I synapses date: 10-06-2021 17:50 gmt revision:1 [0] [head]

Whole-Neuron Synaptic Mapping Reveals Spatially Precise Excitatory/Inhibitory Balance Limiting Dendritic and Somatic Spiking

We mapped over 90,000 E and I synapses across twelve L2/3 PNs and uncovered structured organization of E and I synapses across dendritic domains as well as within individual dendritic segments. Despite significant domain-specific variation in the absolute density of E and I synapses, their ratio is strikingly balanced locally across dendritic segments. Computational modeling indicates that this spatially precise E/I balance dampens dendritic voltage fluctuations and strongly impacts neuronal firing output.

I think this would be tenuous, but they did do patch-clamp recording to back it up, but it's vitally interesting from a structural standpoint. Plus, this is a enjoyable, well-written paper :-)

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ref: -0 tags: synaptic plasticity 2-photon imaging inhibition excitation spines dendrites synapses 2p date: 08-14-2020 01:35 gmt revision:3 [2] [1] [0] [head]

PMID-22542188 Clustered dynamics of inhibitory synapses and dendritic spines in the adult neocortex.

  • Cre-recombinase-dependent labeling of postsynapitc scaffolding via Gephryn-Teal fluorophore fusion.
  • Also added Cre-eYFP to label the neurons
  • Electroporated in utero e16 mice.
    • Low concentration of Cre, high concentrations of Gephryn-Teal and Cre-eYFP constructs to attain sparse labeling.
  • Located the same dendrite imaged in-vivo in fixed tissue - !! - using serial-section electron microscopy.
  • 2230 dendritic spines and 1211 inhibitory synapses from 83 dendritic segments in 14 cells of 6 animals.
  • Some spines had inhibitory synapses on them -- 0.7 / 10um, vs 4.4 / 10um dendrite for excitatory spines. ~ 1.7 inhibitory
  • Suggest that the data support the idea that inhibitory inputs maybe gating excitation.
  • Furthermore, co-inervated spines are stable, both during mormal experience and during monocular deprivation.
  • Monocular deprivation induces a pronounced loss of inhibitory synapses in binocular cortex.

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ref: -2013 tags: 2p two photon STED super resolution microscope synapse synaptic plasticity date: 08-14-2020 01:34 gmt revision:3 [2] [1] [0] [head]

PMID-23442956 Two-Photon Excitation STED Microscopy in Two Colors in Acute Brain Slices

  • Plenty of details on how they set up the microscope.
  • Mice: Thy1-eYFP (some excitatory cells in the hippocampus and cortex) and CX3CR1-eGFP (GFP in microglia). Crossbred the two strains for two-color imaging.
  • Animals were 21-40 days old at slicing.

PMID-29932052 Chronic 2P-STED imaging reveals high turnover of spines in the hippocampus in vivo

  • As above, Thy1-GFP / Thy1-YFP labeling; hence this was a structural study (for which the high resolution of STED was necessary).
  • Might just as well gone with synaptic labels, e.g. tdTomato-Synapsin.

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ref: -0 tags: synaptic plasticity LTP LTD synapses NMDA glutamate uncaging date: 08-11-2020 22:40 gmt revision:0 [head]

PMID-31780899 Single Synapse LTP: A matter of context?

  • Not a great name for a thorough and reasonably well-written review of glutamate uncaging studies as related to LTP (and to a lesser extent LTD).
  • Lots of refernces from many familiar names. Nice to have them all in one place!
  • I'm left wondering, between CaMKII, PKA, PKC, Ras, other GTP dependent molecules -- how much of the regulatory network in synapse is known? E.g. if you pull down all proteins in the synaptosome & their interacting partners, how many are unknown, or have an unknown function? I know something like this has been done for flies, but in mammals - ?

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ref: -2015 tags: PaRAC1 photoactivatable Rac1 synapse memory optogenetics 2p imaging mouse motor skill learning date: 10-30-2019 20:35 gmt revision:1 [0] [head]

PMID-26352471 Labelling and optical erasure of synaptic memory traces in the motor cortex

  • Idea: use Rac1, which has been shown to induce spine shrinkage, coupled to a light-activated domain to allow for optogenetic manipulation of active synapses.
  • PaRac1 was coupled to a deletion mutant of PSD95, PSD delta 1.2, which concentrates at the postsynaptic site, but cannot bind to postsynaptic proteins, thus minimizing the undesirable effects of PSD-95 overexpression.
    • PSD-95 is rapidly degraded by proteosomes
    • This gives spatial selectivity.
  • They then exploited the dendritic targeting element (DTE) of Arc mRNA which is selectively targeted and translated in activiated dendritic segments in response to synaptic activation in an an NMDA receptor dependent manner.
    • Thereby giving temporal selectivity.
  • Construct is then PSD-PaRac1-DTE; this was tested on hippocampal slice cultures.
  • Improved sparsity and labelling further by driving it with the Arc promoter.
  • Motor learning is impaired in Arc KO mice; hence inferred that the induction of AS-PaRac1 by the Arc promoter would enhance labeling during learning-induced potentiation.
  • Delivered construct via in-utero electroporation.
  • Observed rotarod-induced learning; the PaRac signal decayed after two days, but the spine volume persisted in spines that showed Arc / DTE hence PA labeled activity.
  • Now, since they had a good label, performed rotarod training followed by (at variable delay) light pulses to activate Rac, thereby suppressing recently-active synapses.
    • Observed both a depression of behavioral performance.
    • Controlled with a second task; could selectively impair performance on one of the tasks based on ordering/timing of light activation.
  • The localized probe also allowed them to image the synapse populations active for each task, which were largely non-overlapping.

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ref: -2012 tags: phase change materials neuromorphic computing synapses STDP date: 06-13-2019 21:19 gmt revision:3 [2] [1] [0] [head]

Nanoelectronic Programmable Synapses Based on Phase Change Materials for Brain-Inspired Computing

  • Here, we report a new nanoscale electronic synapse based on technologically mature phase change materials employed in optical data storage and nonvolatile memory applications.
  • We utilize continuous resistance transitions in phase change materials to mimic the analog nature of biological synapses, enabling the implementation of a synaptic learning rule.
  • We demonstrate different forms of spike-timing-dependent plasticity using the same nanoscale synapse with picojoule level energy consumption.
  • Again uses GST germanium-antimony-tellurium alloy.
  • 50pJ to reset (depress) the synapse, 0.675pJ to potentiate.
    • Reducing the size will linearly decrease this current.
  • Synapse resistance changes from 200k to 2M approx.

See also: Experimental Demonstration and Tolerancing of a Large-Scale Neural Network (165 000 Synapses) Using Phase-Change Memory as the Synaptic Weight Element

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ref: Legenstein-2008.1 tags: Maass STDP reinforcement learning biofeedback Fetz synapse date: 04-09-2009 17:13 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-18846203[0] A Learning Theory for Reward-Modulated Spike-Timing-Dependent Plasticity with Application to Biofeedback

  • (from abstract) The resulting learning theory predicts that even difficult credit-assignment problems, where it is very hard to tell which synaptic weights should be modified in order to increase the global reward for the system, can be solved in a self-organizing manner through reward-modulated STDP.
    • This yields an explanation for a fundamental experimental result on biofeedback in monkeys by Fetz and Baker.
  • STDP is prevalent in the cortex ; however, it requires a second signal:
    • Dopamine seems to gate STDP in corticostriatal synapses
    • ACh does the same or similar in the cortex. -- see references 8-12
  • simple learning rule they use: d/dtW ij(t)=C ij(t)D(t) d/dt W_{ij}(t) = C_{ij}(t) D(t)
  • Their notes on the Fetz/Baker experiments: "Adjacent neurons tended to change their firing rate in the same direction, but also differential changes of directions of firing rates of pairs of neurons are reported in [17] (when these differential changes were rewarded). For example, it was shown in Figure 9 of [17] (see also Figure 1 in [19]) that pairs of neurons that were separated by no more than a few hundred microns could be independently trained to increase or decrease their firing rates."
  • Their result is actually really simple - there is no 'control' or biofeedback - there is no visual or sensory input, no real computation by the network (at least for this simulation). One neuron is simply reinforced, hence it's firing rate increases.
    • Fetz & later Schimdt's work involved feedback and precise control of firing rate; this does not.
    • This also does not address the problem that their rule may allow other synapses to forget during reinforcement.
  • They do show that exact spike times can be rewarded, which is kinda interesting ... kinda.
  • Tried a pattern classification task where all of the information was in the relative spike timings.
    • Had to run the pattern through the network 1000 times. That's a bit unrealistic (?).
      • The problem with all these algorithms is that they require so many presentations for gradient descent (or similar) to work, whereas biological systems can and do learn after one or a few presentations.
  • Next tried to train neurons to classify spoken input
    • Audio stimului was processed through a cochlear model
    • Maass previously has been able to train a network to perform speaker-independent classification.
    • Neuron model does, roughly, seem to discriminate between "one" and "two"... after 2000 trials (each with a presentation of 10 of the same digit utterance). I'm still not all that impressed. Feels like gradient descent / linear regression as per the original LSM.
  • A great many derivations in the Methods section... too much to follow.
  • Should read refs:
    • PMID-16907616[1] Gradient learning in spiking neural networks by dynamic perturbation of conductances.
    • PMID-17220510[2] Solving the distal reward problem through linkage of STDP and dopamine signaling.

____References____

[0] Legenstein R, Pecevski D, Maass W, A learning theory for reward-modulated spike-timing-dependent plasticity with application to biofeedback.PLoS Comput Biol 4:10, e1000180 (2008 Oct)
[1] Fiete IR, Seung HS, Gradient learning in spiking neural networks by dynamic perturbation of conductances.Phys Rev Lett 97:4, 048104 (2006 Jul 28)
[2] Izhikevich EM, Solving the distal reward problem through linkage of STDP and dopamine signaling.Cereb Cortex 17:10, 2443-52 (2007 Oct)