Accelerated establishment of mature signaling patterns following stimulation of developing neuronal networks: “learning” versus “plasticity”

Zemianek, Jill M.; Lee, Sang-Mook; Guaraldi, Mary; Shea, Thomas B.

doi:10.1016/j.ijdevneu.2012.08.001

Cited by 10 publications

(42 citation statements)

References 45 publications

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“…Long‐term cultures ( i.e. , those maintained for ≥1–2 months) develop spontaneous, complex signals (termed “bursts” by convention) (Madhavan et al, 2007; Rolston et al, 2007; Wagenaar et al, 2006; Zemianek et al, 2012a) that resemble the bursting activity observed during development in situ (Ben‐Ari, 2001; Khazipov et al, 2004; Zhang and Poo, 2001).…”

Section: Introductionmentioning

confidence: 99%

Transient epileptiform signaling during neuronal network development: regulation by external stimulation and bimodal GABAergic activity

Zemianek

Shultz

Lee

et al. 2012

Intl J of Devlp Neuroscience

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A predominance of excitatory activity, with protracted appearance of inhibitory activity, accompanies cortical neuronal development. It is unclear whether or not inhibitory neuronal activity is solicited exclusively by excitatory neurons or whether the transient excitatory activity displayed by developing GABAergic neurons contributes to an excitatory threshold that fosters their conversion to inhibitory activity. We addressed this possibility by culturing murine embryonic neurons on multi-electrode arrays. A wave of individual 0.2-0.4 mV signals ("spikes") appeared between approx. 20-30 days in culture, then declined. A transient wave of high amplitude (>0.5 mV) epileptiform activity coincided with the developmental decline in spikes. Bursts (clusters of ≥3 low-amplitude spikes within 0.7s prior to returning to baseline) persisted following this decline. Addition of the GABAergic antagonist bicuculline initially had no effect on signaling, consistent with delayed development of GABAergic synapses. This was followed by a period in which bicuculline inhibited overall signaling, confirming that GABAergic neurons initially display excitatory activity in ex vivo networks. Following the transient developmental wave of epileptiform signaling, bicuculline induced a resurgence of epileptiform signaling, indicating that GABAergic neurons at this point displayed inhibitory activity. The appearance of transition after the developmental and decline of epileptiform activity, rather than immediately after the developmental decline in lower-amplitude spikes, suggests that the initial excitatory activity of GABAergic neurons contributes to their transition into inhibitory neurons, and that inhibitory GABAergic activity is essential for network development. Prior studies indicate that a minority (25%) of neurons in these cultures were GABAergic, suggesting that inhibitory neurons regulate multiple excitatory neurons. A similar robust increase in signaling following cessation of inhibitory activity in an artificial neural network containing 20% inhibitory neurons supported this conclusion. Even a minor perturbation in GABAergic function may therefore foster initiation and/or amplification of seizure activity, as well as perturbations in long-term potentiation.

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Section: Introductionmentioning

confidence: 99%

Transient epileptiform signaling during neuronal network development: regulation by external stimulation and bimodal GABAergic activity

Zemianek

Shultz

Lee

et al. 2012

Intl J of Devlp Neuroscience

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“…This unique model can be analyzed in detail, and/or expanded upon to encompass additional functionality. Prior studies demonstrated that these networks display alterations in signaling consistent with long-term potentiation following repetitive stimulation with the same digitized synaptic signal utilized herein [4,6]. Embodiment of the neuronal network as described herein provides the unique opportunity for future studies of long-term potentiation by biological neuronal networks in an environmental context.…”

Section: Discussionmentioning

confidence: 82%

“…Signaling was recorded using a MEA-1060-INV amplifier over 30 second intervals and collected via a DT9814 acquisition system and a software program ("Raptor") developed in our laboratory [3,4] (available at https://github.com/ mtgjbird/Raptor). Raptor requires the LabView (National Instruments) run-time engine 2013 SP1 or later http://www.ni.com/download/labview-run-time-engine-2013-sp1/4540/en/.…”

Section: Recording Of Network Activitymentioning

confidence: 99%

See 1 more Smart Citation

Robot-Embodied Neuronal Networks as an Interactive Model of Learning

Shultz¹,

Lee²,

Guaraldi³

et al. 2017

TONEUJ

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Background and Objective:The reductionist approach of neuronal cell culture has been useful for analyses of synaptic signaling. Murine cortical neurons in culture spontaneously form an ex vivo network capable of transmitting complex signals, and have been useful for analyses of several fundamental aspects of neuronal development hitherto difficult to clarify in situ. However, these networks lack the ability to receive and respond to sensory input from the environment as do neurons in vivo. Establishment of these networks in culture chambers containing multi-electrode arrays allows recording of synaptic activity as well as stimulation. Method:This article describes the embodiment of ex vivo neuronal networks neurons in a closed-loop cybernetic system, consisting of digitized video signals as sensory input and a robot arm as motor output. Results:In this system, the neuronal network essentially functions as a simple central nervous system. This embodied network displays the ability to track a target in a naturalistic environment. These findings underscore that ex vivo neuronal networks can respond to sensory input and direct motor output. Conclusion:These analyses may contribute to optimization of neuronal-computer interfaces for perceptive and locomotive prosthetic applications. Ex vivo networks display critical alterations in signal patterns following treatment with subcytotoxic concentrations of amyloid-beta. Future studies including comparison of tracking accuracy of embodied networks prepared from mice harboring key mutations with those from normal mice, accompanied with exposure to Abeta and/or other neurotoxins, may provide a useful model system for monitoring subtle impairment of neuronal function as well as normal and abnormal development.

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“…In this regard, the synaptic signal induced more robust development of neuronal networks in culture than those induced by higher voltage, artificial signals. 42 The findings herein suggest that stimulation with a synaptic signal, and perhaps, additional biological signals, may be useful in physical therapy to promote muscle regeneration/repair.…”

Section: Zemianek Et Almentioning

confidence: 77%