Selective Adaptation in Networks of Cortical Neurons

Faculty of Chemical Engineering, Technion - Israel Institute of Technology, H̱efa, Haifa, Israel
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/2003; 23(28):9349-56.
Source: PubMed


A key property of neural systems is their ability to adapt selectively to stimuli with different features. Using multisite electrical recordings from networks of cortical neurons developing ex vivo, we show that neurons adapt selectively to different stimuli invading the network. We focus on selective adaptation to frequent and rare stimuli; networks were stimulated at two sites with two different stimulus frequencies. When both stimuli were presented within the same period, neurons in the network attenuated their responsiveness to the more frequent input, whereas their responsiveness to the rarely delivered stimuli showed a marked average increase. The amplification of the response to rare stimuli required the presence of the other, more frequent stimulation source. By contrast, the decreased response to the frequent stimuli occurred regardless of the presence of the rare stimuli. Analysis of the response of single units suggests that both of these effects are caused by changes in synaptic transmission. By using synaptic blockers, we find that the increased responsiveness to the rarely stimulated site depends specifically on fast GABAergic transmission. Thus, excitatory synaptic depression, the inhibitory sub-network, and their balance play an active role in generating selective gain control. The observation that selective adaptation arises naturally in a network of cortical neurons developing ex vivo indicates that this is an inherent feature of spontaneously organizing cortical networks.

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Available from: Danny Eytan, Sep 17, 2014
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    • "In cortical cultures a variety of stimulation protocols have been used, for example, to control the oscillatory population activity as a putative treatment for epilepsy (Wagenaar et al., 2005), to study adaptation phenomena (Eytan et al., 2003; Wagenaar et al., 2006b) or neuronal plasticity (Jimbo et al., 1998, 1999; Tateno and Jimbo, 1999; Shahaf and Marom, 2001; Bakkum et al., 2008; Chiappalone et al., 2008; Stegenga et al., 2009; Bologna et al., 2010). The protocols used range from long-term low frequency (Wagenaar et al., 2006b; Vajda et al., 2008; Bologna et al., 2010) to high frequency 'tetanic' stimuli (Jimbo et al., 1998, 1999; Wagenaar et al., 2006b; Chiappalone et al., 2008). "
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    ABSTRACT: The modulation of neuronal activity by means of electrical stimulation is a successful therapeutic approach for patients suffering from a variety of central nervous system disorders. Prototypic networks formed by cultured cortical neurons represent an important model system to gain general insights in the input-output relationships of neuronal tissue. These networks undergo a multitude of developmental changes during their maturation, such as the excitatory-inhibitory shift of the neurotransmitter GABA. Very few studies have addressed how the output properties to a given stimulus change with ongoing development. Here, we investigate input-output relationships of cultured cortical networks by probing cultures with and without functional GABAAergic synaptic transmission with a set of stimulation paradigms at various stages of maturation. On the cellular level, low stimulation rates (<15 Hz) led to reliable neuronal responses; higher rates were increasingly ineffective. Similarly, on the network level, lowest stimulation rates (<0.1 Hz) lead to maximal output rates at all ages, indicating a network wide refractory period after each stimulus. In cultures aged 3 weeks and older, a gradual recovery of the network excitability within tens of milliseconds was in contrast to an abrupt recovery after about 5 s in cultures with absent GABAAergic synaptic transmission. In these GABA deficient cultures evoked responses were prolonged and had multiple discharges. Furthermore, the network excitability changed periodically, with a very slow spontaneous change of the overall network activity in the minute range, which was not observed in cultures with absent GABAAergic synaptic transmission. The electrically evoked activity of cultured cortical networks, therefore, is governed by at least two potentially interacting mechanisms: A refractory period in the order of a few seconds and a very slow GABA dependent oscillation of the network excitability.
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    • "Antunes and Malmierca (2011) showed that the possible inhibition driven by the corticofugal pathway did not underlie SSA in the MGB neurons, since the neurons maintained SSA during AC deactivation. Hence, if inhibition plays a role in SSA, as has been suggested in previous studies (Eytan et al., 2003; Yu et al., 2009; Richardson et al., 2011; Duque et al., 2014), other pathways should be involved, such as those coming from the IC (Peruzzi et al., 1997), the TRN-MGB connections themselves (Yu et al., 2009), as well as non-AC inputs to the TRN from basal forebrain (Hallanger and Wainer, 1988; Asanuma and Porter, 1990; Bickford et al., 1994), amygdala (Zikopoulos and Barbas, 2012), prefrontal cortex (Zikopoulos and Barbas, 2006), and GABAergic inputs from zona incerta (Cavdar et al., 2006). It may be that in the highly adaptive neurons, the suppressive effect exerted by the corticofugal pathway on the general responses of the neuron helps to increase the contrast between the standard and the deviant, as in the " iceberg effect " (Carandini and Ferster, 2000; Isaacson and Scanziani, 2011; Katzner et al., 2011. "
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    • "The said reduced preparation is a large-scale cortical network developing in vitro, on top of a substrate integrated multi-electrode array (MEA). This preparation proved useful, over the past 10–15 years, as a toy model in the study of functional network processes, ranging from development and adaptation to learning and stimulus representation (Maeda et al., 1995; Kamioka et al., 1996; Jimbo et al., 1998, 1999; Tateno and Jimbo, 1999; Shahaf and Marom, 2001; Corner et al., 2002; Eytan et al., 2003; Shahaf et al., 2008). A recent series of studies demonstrated the efficacy of several closed loop applications in controlling aspects of activity in these in vitro large-scale cortical networks (e.g., Wagenaar and Potter, 2004; Wagenaar et al., 2005; Arsiero et al., 2007; Rolston et al., 2010; Wallach et al., 2011; Weihberger et al., 2013). "
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    ABSTRACT: In recent years much effort is invested in means to control neural population responses at the whole brain level, within the context of developing advanced medical applications. The tradeoffs and constraints involved, however, remain elusive due to obvious complications entailed by studying whole brain dynamics. Here, we present effective control of response features (probability and latency) of cortical networks in vitro over many hours, and offer this approach as an experimental toy for studying controllability of neural networks in the wider context. Exercising this approach we show that enforcement of stable high activity rates by means of closed loop control may enhance alteration of underlying global input-output relations and activity dependent dispersion of neuronal pair-wise correlations across the network.
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