Stimulation triggers endogenous activity patterns in cultured cortical networks

Pasquale, Valentina; Martinoia, Sergio; Chiappalone, Michela

doi:10.1038/s41598-017-08369-0

Cited by 37 publications

(29 citation statements)

References 81 publications

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“…Notably, in our cellular model of excitotoxicity, pretreatment with BDNF for 1 h could not prevent the decrease in neuronal viability () or interfere the processing of TrkB‐FL () induced by NMDA. Basal TrkB activation, observed in this experiment (, lower panels) as before (Du et al , ; Gomes et al , ; Vidaurre et al , ), might be due to spontaneous neuronal activity of dissociated cultures (Pasquale et al , ) and mediated by calcium‐influx through NMDARs and calcium channels (Du et al , ). Next, we were interested in establishing the phosphorylation status of the TrkB‐FL receptor preserved in excitotoxic conditions by TFL 457 action.…”

Section: Resultssupporting

confidence: 76%

Prevention of excitotoxicity‐induced processing of BDNF receptor TrkB‐FL leads to stroke neuroprotection

et al. 2019

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Neuroprotective strategies aimed to pharmacologically treat stroke, a prominent cause of death, disability, and dementia, have remained elusive. A promising approach is restriction of excitotoxic neuronal death in the infarct penumbra through enhancement of survival pathways initiated by brain‐derived neurotrophic factor (BDNF). However, boosting of neurotrophic signaling after ischemia is challenged by downregulation of BDNF high‐affinity receptor, full‐length tropomyosin‐related kinase B (TrkB‐FL), due to calpain‐degradation, and, secondarily, regulated intramembrane proteolysis. Here, we have designed a blood–brain barrier (BBB) permeable peptide containing TrkB‐FL sequences (TFL 457 ) which prevents receptor disappearance from the neuronal surface, early induced after excitotoxicity. In this way, TFL 457 interferes TrkB‐FL cleavage by both proteolytic systems and increases neuronal viability via a PLCγ‐dependent mechanism. By preserving downstream CREB and MEF2 promoter activities, TFL 457 initiates a feedback mechanism favoring increased levels in excitotoxic neurons of critical prosurvival mRNAs and proteins. This neuroprotective peptide could be highly relevant for stroke therapy since, in a mouse ischemia model, it counteracts TrkB‐FL downregulation in the infarcted brain, efficiently decreases infarct size, and improves neurological outcome.

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Section: Resultssupporting

confidence: 76%

Prevention of excitotoxicity‐induced processing of BDNF receptor TrkB‐FL leads to stroke neuroprotection

et al. 2019

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“…Similarity between spontaneous and evoked activity patterns was previously described in a number of in vivo studies [33] [34] and a recent study has confirmed such observation in vitro [35]. In this work, similarly to what previously described [12,27,29,30] we employed polymeric structures made of polydimtheylsiloxane (PDMS) for confining neurons (Mata et al, 2005;Liu et al, 2005;del Campo & Greiner, 2007Jackman et al, 1999 to induce the self-organization of networks into inter-connected spatially defined neuronal assemblies.…”

Section: Introductionsupporting

confidence: 74%

The emergence of dynamical instantaneous memory in the spontaneous activity of spatially confined neuronal assemblies in vitro

Piasetzky

Bisio

Kanner

et al. 2018

Preprint

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Understanding the dynamics between communicating cell assemblies is essential for deciphering the neural code and identifying the mechanism underlying memory formation. In this work, in order to unveil possible emergent intrinsic memory phenomena in the communication between cell assemblies, we study the spontaneous dynamics of in vitro spatially confined inter-connected neuronal circuits grown on multi-electrode arrays. The spontaneous dynamics of the global network was characterized by the coupling of the activity independently generated by each circuit.The asymptotic functional connectivity of the network reflected its modular organization. Instantaneous functional connectivity maps on ten seconds epochs, revealed more complex dynamical states with the simultaneous activation of distinct circuits. When looking at the similarity of the generated network events, we observed 2 that spontaneous network events occurring at temporal distances below two dozens of seconds had an average higher similarity compared to randomly played network events. Such a memory phenomenon was not observed in networks where spontaneous events were less frequent and in networks topologically organized as open lines. These results support the hypothesis that dynamical instantaneous memory, characterized by drifting network dynamics with decaying degree of similarity, is an intrinsic property of neuronal networks.

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“…Another important ingredient of the network connectivity in our model is the presence of a small percentage of neurons that has higher incoming connection strengths, and is responsible for focusing the noise and initiating the collective activity (and avalanche propagation). The presence of a few highly active sites, driving cortical neural activity (leaders), has been reported experimentally [29,[70][71][72]. Notably it has been shown that these leader sites are reliably and rapidly recruited within both spon-taneous and evoked bursts [71].…”

Section: Discussionmentioning

confidence: 99%

Hysteresis, neural avalanches, and critical behavior near a first-order transition of a spiking neural network

et al. 2018

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Many experimental results, both in vivo and in vitro, support the idea that the brain cortex operates near a critical point and at the same time works as a reservoir of precise spatiotemporal patterns. However, the mechanism at the basis of these observations is still not clear. In this paper we introduce a model which combines both these features, showing that scale-free avalanches are the signature of a system posed near the spinodal line of a first-order transition, with many spatiotemporal patterns stored as dynamical metastable attractors. Specifically, we studied a network of leaky integrate-and-fire neurons whose connections are the result of the learning of multiple spatiotemporal dynamical patterns, each with a randomly chosen ordering of the neurons. We found that the network shows a first-order transition between a low-spiking-rate disordered state (down), and a high-rate state characterized by the emergence of collective activity and the replay of one of the stored patterns (up). The transition is characterized by hysteresis, or alternation of up and down states, depending on the lifetime of the metastable states. In both cases, critical features and neural avalanches are observed. Notably, critical phenomena occur at the edge of a discontinuous phase transition, as recently observed in a network of glow lamps.

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Stimulation triggers endogenous activity patterns in cultured cortical networks

Cited by 37 publications

References 81 publications

Prevention of excitotoxicity‐induced processing of BDNF receptor TrkB‐FL leads to stroke neuroprotection

Prevention of excitotoxicity‐induced processing of BDNF receptor TrkB‐FL leads to stroke neuroprotection

The emergence of dynamical instantaneous memory in the spontaneous activity of spatially confined neuronal assemblies in vitro

Hysteresis, neural avalanches, and critical behavior near a first-order transition of a spiking neural network

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