Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Here we present a model that is based on self-organized criticality and takes into account brain plasticity, which is able to reproduce the spectrum of electroencephalograms (EEG). The model consists of an electrical network with threshold firing and activity-dependent synapse strengths. The system exhibits an avalanche activity in a power-law distribution. The analysis of the power spectra of the electrical signal reproduces very robustly the power-law behavior with the exponent 0.8, experimentally measured in EEG spectra. The same value of the exponent is found on small-world lattices and for leaky neurons, indicating that universality holds for a wide class of brain models.

Neuronal avalanches, measured in vitro and in vivo, exhibit a robust critical behaviour. Their temporal organization hides the presence of correlations. Here we present experimental measurements of the waiting time distribution between successive avalanches in the rat cortex in vitro. This exhibits a non-monotonic behaviour, not usually found in other natural processes. Numerical simulations provide evidence that this behaviour is a consequence of the alternation between states of high and low activity, named up and down states, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homeostatic mechanisms.PACS numbers: 05.65.+b, 05.45.Tp, 87.19.LSpontaneous neuronal activity can exhibit slow oscillations between bursty periods, or up-states, followed by substantially quiet periods. Bursts can last from a few to several hundreds of milliseconds and, if analysed at a finer temporal scale, have often shown a complex structure in terms of neuronal avalanches. In vitro experiments record avalanche activity [1,2] from mature organotypic cultures of rat somatosensory cortex where they spontaneously emerge in superficial layers. The size and duration of neuronal avalanches follow power law distributions with stable exponents, which is a typical feature of a system in a critical state, where large fluctuations are present and the response does not have a characteristic size. The same critical behaviour has been measured in vivo from rat cortical layers during early post-natal development [3], from the cortex of awake adult rhesus monkeys[4], using microelectrode array recordings, as well as for dissociated neurons from rat hippocampus [5,6] or leech ganglia [5]. In vitro, quiet periods measured between bursts, also called down-states, can last up to several seconds. The emergence of these down-states can be attributed to various mechanisms: a decrease in the neurotransmitter released, either due to the exhaustion of available synaptic vesicles or to the increase of a factor inhibiting the release [7] such as the nucleoside adenosine[8], the blockade of receptor channels by the presence of external magnesium [9], or else spike adaptation [10]. A down-state is then characterized by a disfacilitation, i.e. absence of synaptic activity, of a large number of neurons causing long-lasting returns to resting potentials [11]. Recently, it was shown analytically and numerically that critical behaviour[12] characterizes up-states, whereas down-states are subcritical [13].Whereas action potentials are rare during down-states, small amplitude depolarizing potentials, reminiscent of miniature potentials from spontaneous synaptic release, occur at higher frequencies. The non-linear amplification of small amplitude signals contributes to the generation of larger depolarizing events bringing the system back into the up-state, as observed in cortical slabs [14], dissociated c...

The extracellular-signal regulated kinases 1/2 (ERK or ERKs) are involved in the regulation of important neuronal functions, including neuronal plasticity in normal and pathological conditions. We present findings that support the notion that the kinetics and localization of ERK are intrinsically linked, in that the duration of ERK activation dictates its subcellular compartmentalization and/or trafficking. The latter, in turn, dictates whether ERK-expressing cells would enter a program of cell death, survival or differentiation. We summarize experimental data showing that chronic activation of ERK plays a role in the mechanisms that trigger neurodegeneration. We also discuss how MKPs, members of the subclass of dual specificity phosphatases, might be the link between ERK kinetics and its subcellular localization.

Administration of methylphenidate (MPH, Ritalins ) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-related and motivational-choice behaviors. When tested in adulthood in a drug-free state, MPH-pretreated animals showed increased choice flexibility and economical efficiency, as well as a dissociation between dampened place conditioning and more marked locomotor sensitization induced by cocaine, compared to SALpretreated controls. The striatal complex, a core component of the natural reward system, was collected both at the end of the MPH treatment and in adulthood. Genome-wide expression profiling, followed by RT-PCR validation on independent samples, showed that three members of the postsynaptic-density family and five neurotransmitter receptors were upregulated in the adolescent striatum after subchronic MPH administration. Interestingly, only genes for the kainate 2 subunit of ionotropic glutamate receptor (Grik2, also known as KA2) and the 5-hydroxytryptamine (serotonin) receptor 7 (Htr7) (but not GABA A subunits and adrenergic receptor a1b) were still upregulated in adulthood. cAMP responsive element-binding protein and Homer 1a transcripts were modulated only as a long-term effect. In summary, our data indicate short-term changes in neural plasticity, suggested by modulation of expression of key genes, and functional changes in striatal circuits. These modifications might in turn trigger enduring changes responsible for the adult neurobehavioral profile, that is, altered processing of incentive values and a modified flexibility/habit balance.