A: Cortical network on substrate-embedded multi-electrode array. The dark circle is a 30-μm-diameter electrode. Neurons are tagged using green fluorescent protein. B: Example of spontaneous activity simultaneously … In recent works by us and others the basic properties of the network spike were described.21–24 It is a synchronized population event Selleck Idelalisib governed by a threshold, which follows the logistics of neuronal recruitment

in an effectively scale-free connected network. The sequence of neuronal activation within these spikes is non-random and follows a hierarchy that is probably dictated by the topology of connections. We have also shown that using prior knowledge of this recruitment pattern Inhibitors,research,lifescience,medical the appearance of a network spike can be reliably predicted and used to alter and manipulate activity within and between neuronal assemblies.21,25–28 The effects of stimulation on these networks have also been extensively studied. It has been shown that extracellular electrical Inhibitors,research,lifescience,medical stimulation from spatially different sources elicits prototypical responses in the form of network spikes. These spikes exhibit two distinct phases of response

– an early, directly activated response in which action potential latencies are well preserved and a later, “downstream” Inhibitors,research,lifescience,medical phase elicited by reverberation of activity which Inhibitors,research,lifescience,medical is very variable.29,30 Each neuron typically fires many action potentials in each network spike as it is being activated by many different propagation pathways (Figure 2). Figure 2 The evoked network spike (NS). All the panels are examples from a single experiment. A: An example of a single, stimulus-evoked NS. Each line is a raster plot of a single electrode. B: Population firing rate profiles of NS (population-count-histogram … The ability to stimulate electrically at different spatial locations, different repetition rates and stimulus amplitudes, over extended periods (up to weeks) allows a detailed characterization of the input-output

properties of these networks – as either models for Inhibitors,research,lifescience,medical a generic neuronal assembly. Thus, we consider these networks as single entities, pooling together all the activity of the neurons comprising the network. In general there seems to be a monotonically albeit threshold-governed relationship between the stimulation amplitude and response amplitude and an inverse relation to the response latency. Moreover, it seems that as the stimulation frequency is increased, adaption processes kick in: when the stimulation frequency is “high” enough (i.e. 0.2–1 Hz) the network response initially undergoes a period of habituation, which is stimulus site-specific,31 but over time a complex non-trivial pattern of responsiveness emerges with response latency fluctuations exhibiting long-term correlations (Figures 2 and ​and3).3).