Synaptic dynamics contribute to long-term single neuron response fluctuations

Reinartz, Sebastian; Bíró, István; Gal, A.; Giugliano, Michèle; Marom, Shimon

doi:10.3389/fncir.2014.00071

Cited by 26 publications

(28 citation statements)

References 54 publications

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“…6D) activity. Other groups have also reported that blocking AMPA receptors is enough to abolish this activity (Bonzano et al 2006;Reinartz et al 2014). Furthermore, in a network that is driven uniquely by AMPA receptors, we did find maximal spike rates (Fig.…”

Section: Discussionsupporting

confidence: 62%

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents

Suresh

Radojicic

Pesce

et al. 2016

Journal of Neurophysiology

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AK, Marks JD, van Drongelen W. Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents. J Neurophysiol 115: 3073-3089, 2016. First published March 16, 2016 doi:10.1152/jn.00995.2015.-The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while shorttimescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Na p ) currents govern burst onset during interburst intervals. To test this, we used synaptic receptor antagonists picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP) to selectively block GABA A , AMPA, and NMDA receptors and riluzole to selectively block Na p channels. We systematically compared intracellular activity (recorded with patch clamp) and network activity (recorded with multielectrode arrays) in eight different synaptic connectivity conditions: GABA A ϩ NMDA ϩ AMPA, NMDA ϩ AMPA, GABA A ϩ AMPA, GABA A ϩ NMDA, AMPA, NMDA, GABA A , and all receptors blocked. Furthermore, we used mixed-effects modeling to quantify the aforementioned independent and interactive synaptic receptor contributions toward spectro-temporal burst properties including intraburst spike rate, burst activity index, burst duration, power in the local field potential, network connectivity, and transmission delays. We found that blocking intrinsic Na p currents completely abolished bursting activity, demonstrating their critical role in burst onset within the network. On the other hand, blocking different combinations of synaptic receptors revealed that spectro-temporal burst properties are uniquely associated with synaptic functionality and that excitatory connectivity is necessary for the presence of network-wide bursting. In addition to confirming the critical contribution of direct excitatory effects, mixed-effects modeling also revealed distinct combined (nonlinear) contributions of excitatory and inhibitory synaptic activity to network bursting properties. epilepsy; multielectrode arrays; network bursting; pharmacology; synaptic mechanisms SPONTANEOUS NETWORK-WIDE SYNCHRONIZED bursting activity appears to play an important role in several aspects of the nervous system including development (Gu and Spitzer 1995;Meister et al. 1991;Shatz 1990;Yuste et al. 1992) and integration in the sensory system (Engel et al. 1992) but also in the initiation of pathological activity such as epileptic seizures (Gutnick et al. 1982;Miles and Wong 1983). Therefore, clarifying how the underlying synaptic and intrinsic neuronal properties modulate and cause this network behavior is likely to provide valuable under...

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Section: Discussionsupporting

confidence: 62%

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents

Suresh

Radojicic

Pesce

et al. 2016

Journal of Neurophysiology

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“…Electrophysiology and MEA recordings. Primary cortical cultures were obtained from postnatal Wistar rats, employing standard methods 34 . Briefly, after mechanical and enzymatic dissociation of the cerebral cortices of postnatal day 0 (P0) pups, cells were plated at a final density of ,1.500 mm 22 on glass coverslips and of 6.500 mm 22 on commercial microelectrode arrays (MEAs; Multichannel Systems GmBH, Reutlingen, Germany).…”

Section: Research Lettermentioning

confidence: 99%

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration

Peelaerts

Bousset

Perren

et al. 2015

Nature

989

974

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Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.

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“…In vitro, we used a single stimulation electrode to directly (nonsynaptically) activate multiple neurons (Marom and Shahaf 2002;Wagenaar et al 2004;Reinartz et al 2014), and in simulations, we directly activated a set of neurons, which was usually sufficient to trigger a network burst. Stimuli were applied either as low-frequency pulses or as tetani.…”

Section: Discussionmentioning

confidence: 99%

Repeated stimulation of cultured networks of rat cortical neurons induces parallel memory traces

et al. 2015

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During systems consolidation, memories are spontaneously replayed favoring information transfer from hippocampus to neocortex. However, at present no empirically supported mechanism to accomplish a transfer of memory from hippocampal to extra-hippocampal sites has been offered. We used cultured neuronal networks on multielectrode arrays and small-scale computational models to study the effect of memory replay on the formation of memory traces. We show that input-deprived networks develop an activity⇔connectivity balance where dominant activity patterns support current connectivity. Electrical stimulation at one electrode disturbs this balance and induces connectivity changes. Intrinsic forces in recurrent networks lead to a new equilibrium with activity patterns that include the stimulus response. The new connectivity is no longer disrupted by this stimulus, indicating that networks memorize it. A different stimulus again induces connectivity changes upon first application but not subsequently, demonstrating the formation of a second memory trace. Returning to the first stimulus does not affect connectivity, indicating parallel storage of both traces. A computer model robustly reproduced experimental results, suggesting that spike-timing-dependent plasticity and short time depression suffice to store parallel memory traces, even in networks without particular circuitry constraints.

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Synaptic dynamics contribute to long-term single neuron response fluctuations

Cited by 26 publications

References 54 publications

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration

Repeated stimulation of cultured networks of rat cortical neurons induces parallel memory traces

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