Orchestration of "presto" and "largo" synchrony in up-down activity of cortical networks

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.

Physiological characterization of human muscle acetylcholine receptors from ALS patients

“…Riluzole blocks voltagegated sodium channels plus a variety of other channels (33)(34)(35) and inhibits ACh currents in transfected cell lines at very high concentrations (17). However, to date there have been no studies of AChRs in ALS muscles (2).…”

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

“…For each parameter, data were computed in half-hour time segments and identified as time points in the experiment's plots corresponding to the control and treatment time course. 22,24,25,28 analysis of MsNP protein coronas by sDs-Page MSNPs (0.25 mg/mL) of each size were incubated under constant movement with 1 mL of completed cell-culture medium with 5% or 10% of serum at 37°C for 24 hours. After incubation, samples were centrifuged at 1,000× g for 20 minutes at room temperature to remove unbound proteins from NP surfaces.…”

“…Such in vitro activity can be recorded by MEA technology in a noninvasive way, with good temporal and spatial resolution, as described previously. 22,24,25 Briefly, raw analogue signals were sampled at 40 kHz using MEA-1060-INV preamplifiers (bandwidth 0.1-8 kHz; MultiChannel Systems) and an MEA Workstation (bandwidth 0.1-8 kHz; Plexon, Dallas, TX, USA). Offline Sorter software (Plexon) was used to clean data appropriately from artifacts and assign spikes into multiunit (1-4) electrodes by using principal-component analysis-based software.…”

Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony

“…In contrast, reduced activity of these systems, which occurs mainly during periods of NREM (non rapid eye movement) sleep, is associated with the prominent appearance of network synchrony as defined above. Importantly, however, neither these forms of network synchrony nor their modulation by acetylcholine (ACh) and noradrenaline (NA) are limited to the intact cortex, as similar activity patterns occur in brain slabs [21], acute and organotypic cortical preparations (for example, [22][23][24][25][26]) and even in networks of dissociated cortical neurons (for example, [27][28][29][30][31][32][33][34][35][36][37]; reviewed in [38]). …”

“…Where networks of dissociated cortical neurons in culture are concerned, synchrony takes the form of networkwide bursting activity which lasts for several hundreds of milliseconds, separated by longer periods (1 to 10 seconds) of near-complete quiescence or sparse, asynchronous action potentials [27][28][29][30][31][32][33][34][35][36][37]. These network-wide bursts are less frequent and more stereotyped as compared to those observed in the intact brain, which might be expected given the smaller size and lower connection density of these networks as well as the lack of reentrant pathways [21,[39][40][41]).…”