Critical role for inhibitory neurons in modulation of synaptic signaling in <i>ex vivo</i> neuronal networks

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

doi:10.1016/j.ijdevneu.2013.03.011

Cited by 6 publications

(26 citation statements)

References 41 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 85%

Robot-Embodied Neuronal Networks as an Interactive Model of Learning

Shultz¹,

Lee²,

Guaraldi³

et al. 2017

TONEUJ

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 85%

Robot-Embodied Neuronal Networks as an Interactive Model of Learning

Shultz¹,

Lee²,

Guaraldi³

et al. 2017

TONEUJ

Self Cite

View full text Add to dashboard Cite

show abstract

“…Monitoring of signal patterns further demonstrated that bursts appeared relatively early and did not change in frequency during development, but that higher‐amplitude individual spikes underwent a developmental decline. The more detailed analyses presented herein, coupled with the resurgence of high‐amplitude spikes following suppression of inhibitory activity, suggested progressive elimination of spikes played a major role in the establishment of the mature signaling pattern (Zemianek et al, 2013a). Our studies of individual signal patterns herein further extend these considerations by demonstrating that suppression of inhibitory activity shifts the predominance of signals toward those containing relatively high‐amplitude spikes.…”

Section: Discussionmentioning

confidence: 89%

“…Prior studies from multiple laboratories demonstrate that cultured neurons initially elaborate predominantly high‐amplitude spikes, and by >30 days after plating establish a so‐called mature pattern of signals that consists of complex bursts of varying amplitude and duration along with a relatively fewer spikes (van Pelt et al, 2004a,b; Madhavan et al, 2005; Wagenaar et al, 2006; Ikegaya et al, 2008; Chiappalone et al, 2009; Zemianek et al, 2012a,b, 2013a,b). We first confirmed that this was also the case in our current networks.…”

Section: Resultsmentioning

confidence: 99%

“…For some experiments, signal patterns were quantified before and 1 h after the addition of 5 μM bicuculline to mature networks (42 days after plating, by which time inhibitory neurons are fully active; Zemianek et al, 2013a).…”

Section: Methodsmentioning

confidence: 99%

“…Cultured embryonic neurons develop networks that transmit synaptic signals over multiple sequentially connected neurons as revealed by multi‐electrode arrays (MEAs) embedded within the culture dish (Wagenaar et al, 2004; Morin et al, 2005; Zemianek et al, 2012a,b, 2013a,b). Signals generated by such ex vivo networks convert over the course of approximately one month in culture from a pattern predominated by high‐amplitude individual spikes to a “mature” pattern that is rich in complex bursts (van Pelt et al, 2004a,b; Madhavan et al, 2005; Wagenaar et al, 2006; Ikegaya et al, 2008; Chiappalone et al, 2009; Zemianek et al, 2012a,b, 2013a,b). Establishment of this mature pattern is dependent upon a critical neuronal density and a balance of inhibitory and excitatory activity (Serra et al, 2010; Zemianek et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synaptic signal streams generated by ex vivo neuronal networks contain non‐random, complex patterns

Lee

Zemianek

Shultz

et al. 2014

Intl J of Devlp Neuroscience

Self Cite

View full text Add to dashboard Cite

Cultured embryonic neurons develop functional networks that transmit synaptic signals over multiple sequentially connected neurons as revealed by multi-electrode arrays (MEAs) embedded within the culture dish. Signal streams of ex vivo networks contain spikes and bursts of varying amplitude and duration. Despite the random interactions inherent in dissociated cultures, neurons are capable of establishing functional ex vivo networks that transmit signals among synaptically connected neurons, undergo developmental maturation, and respond to exogenous stimulation by alterations in signal patterns. These characteristics indicate that a considerable degree of organization is an inherent property of neurons. We demonstrate herein that (1) certain signal types occur more frequently than others, (2) the predominant signal types change during and following maturation, (3) signal predominance is dependent upon inhibitory activity, and (4) certain signals preferentially follow others in a non-reciprocal manner. These findings indicate that the elaboration of complex signal streams comprised of a non-random distribution of signal patterns is an emergent property of ex vivo neuronal networks.

show abstract

Insufficient developmental excitatory neuronal activity fails to foster establishment of normal levels of inhibitory neuronal activity

Therrien

Vohnoutka

Boumil

et al. 2016

Intl J of Devlp Neuroscience

Self Cite

View full text Add to dashboard Cite

The nervous system is composed of excitatory and inhibitory neurons. One major class of inhibitory neurons release the neurotransmitter γ-Aminobutyric acid (GABA). GABAergic inhibitory activity maintains the balance that is disrupted in conditions such as epilepsy. At least some GABAergic neurons are initially excitatory and undergo a developmental conversion to convert to inhibitory neurons. The mechanism(s) behind this conversion are thought to include a critical developmental increase in excitatory activity. To test this hypothesis, we subjected ex vivo developing neuronal networks on multi-electrode arrays to various stimulation and pharmacological regimens. Synaptic activity of networks initially consists of epileptiform-like high-amplitude individual "spikes", which convert to organized bursts of activity over the course of approximately 1 month. Stimulation of networks with a digitized synaptic signal for 5days hastened the decrease of epileptiform activity. By contrast, stimulation for a single day delayed the appearance of bursts and instead increased epileptiform signaling. GABA treatment reduced total signals in unstimulated networks and networks stimulated for 5days, but instead increased signaling in networks stimulated for 1day. This increase was prevented by co-treatment with (2R)-amino-5-phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione, confirming that GABA invoked excitatory activity in networks stimulated for 1day. Glutamate increased signals in networks subjected to all stimulation regimens; the GABA receptor antagonist bicuculline prevented this increase only in networks stimulated for 1day. These latter findings are consistent with the induction of so-called "mixed" synapses (which release a combination of excitatory and inhibitory neurotransmitters) in networks stimulated for 1day, and support the hypothesis that a critical level of excitatory activity fosters the developmental transition of GABAergic neurons from excitatory to inhibitory.

show abstract

Critical role for inhibitory neurons in modulation of synaptic signaling in ex vivo neuronal networks

Cited by 6 publications

References 41 publications

Robot-Embodied Neuronal Networks as an Interactive Model of Learning

Robot-Embodied Neuronal Networks as an Interactive Model of Learning

Synaptic signal streams generated by ex vivo neuronal networks contain non‐random, complex patterns

Insufficient developmental excitatory neuronal activity fails to foster establishment of normal levels of inhibitory neuronal activity

Contact Info

Product

Resources

About