Abstract
It has been demonstrated using single-cell and multiunit electrophysiology in layer III entorhinal cortex and disinhibited hippocampal CA3 slices that the balancing of the up-down activity is characterized by both GABAA and GABAB mechanisms. Here we report novel results obtained using multi-electrode array (60 electrodes) simultaneous recordings from reverberating postnatal neocortical networks containing 19.2 ± 1.4% GABAergic neurons, typical of intact tissue. We observed that in each spontaneous active-state the total number of spikes in identified clusters of excitatory and inhibitory neurons is almost equal, thus suggesting a balanced average activity. Interestingly, in the active-state, the early phase is sustained by only 10% of the total spikes and the firing rate follows a sigmoidal regenerative mode up to peak at 35 ms with the number of excitatory spikes greater than inhibitory, therefore indicating an early unbalance. Concentration-response pharmacology of up- and down-state lifetimes in clusters of excitatory (n = 1067) and inhibitory (n = 305) cells suggests that, besides the GABAA and GABAB mechanisms, others such as GAT-1-mediated uptake, Ih, INaP and IM ion channel activity, robustly govern both up- and down-activity. Some drugs resulted to affect up- and/or down-states with different IC50s, providing evidence that various mechanisms are involved. These results should reinforce not only the role of synchrony in CNS networks, but also the recognized analogies between the Hodgkin–Huxley action potential and the population bursts as basic mechanisms for originating membrane excitability and CNS network synchronization, respectively.
Highlights
Action potential (AP) propagation and synaptic transmission are shared by both peripheral and central nervous systems to sustain fast responding excitability
This distribution was frequently observed in the central area of cultures, whereas neuronal cells endowed with large cell bodies and extensive processes became more scattered in the periphery
The selective immunocytochemical staining for GABAergic cells showed inhibitory interneurons scattered in the network; they mainly appeared in the external part of clusters (Figures 1B,C,E,F)
Summary
Action potential (AP) propagation and synaptic transmission are shared by both peripheral and central nervous systems to sustain fast responding excitability Both systems are constitutively acted upon by several fundamental but conflicting properties such as serial or parallel activity, rate or temporal spike coding, independent or synchronous operation, reliable or unreliable synaptic transmission, respectively (Otmakhov et al, 1993; Lisman, 1997). Recorded neural signals such as those recorded from multi-electrode arrays (MEAs) consist of time-varying spatial distributions of APs (“spikes”, 1 ms) superimposed on relatively slow local field potentials (LFP, 1–2 s). Recordings from MEA dishes are governed by sets of excitatory and inhibitory synaptic transmission systems that have been described as consisting of indistinguishable cells capable of generating either spikes during synchronous bursting in cortical cultures in vitro (Keefer et al, 2001; Giugliano et al, 2004; Gramowski et al, 2004; Selinger et al, 2004; Van Pelt et al, 2004; Martinoia et al, 2005; Tateno et al, 2005; Eytan and Marom, 2006; Wagenaar et al, 2006), or LFPs in organotypic cultures and slices (Beggs and Plenz, 2003, 2004; Sun and Luhmann, 2007)
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