Spontaneous neuronal activity is an important property of the cerebral cortex but its spatiotemporal organization and dynamical framework remain poorly understood. Studies in reduced systems-tissue cultures, acute slices, and anesthetized ratsshow that spontaneous activity forms characteristic clusters in space and time, called neuronal avalanches. Modeling studies suggest that networks with this property are poised at a critical state that optimizes input processing, information storage, and transfer, but the relevance of avalanches for fully functional cerebral systems has been controversial. Here we show that ongoing cortical synchronization in awake rhesus monkeys carries the signature of neuronal avalanches. Negative LFP deflections (nLFPs) correlate with neuronal spiking and increase in amplitude with increases in local population spike rate and synchrony. These nLFPs form neuronal avalanches that are scale-invariant in space and time and with respect to the threshold of nLFP detection. This dimension, threshold invariance, describes a fractal organization: smaller nLFPs are embedded in clusters of larger ones without destroying the spatial and temporal scale-invariance of the dynamics. These findings suggest an organization of ongoing cortical synchronization that is scale-invariant in its three fundamental dimensions-time, space, and local neuronal group size. Such scale-invariance has ontogenetic and phylogenetic implications because it allows large increases in network capacity without a fundamental reorganization of the system. neuronal synchronization ͉ resting state ͉ rhesus monkey ͉ spontaneous activity ͉ ongoing activity T he cerebral cortex displays spontaneous activity, also known as 'ongoing' or 'resting state' activity, which persists in the absence of sensory stimuli or motor outputs. The ongoing activity is a robust feature of cortical dynamics as it is only modulated to a small extent by stimulus presentation (1), but contributes significantly to the large variability observed in stimulus responses (2-5). In fact, ongoing activity has been found to reflect multiple aspects of neuronal processing. The activity is similar to that observed during stimulus presentation (1, 6-8), incorporates previously acquired information (9), and carries information about the underlying neuronal network [for review see (10)]. Indeed, correlations during resting state activity are altered in disease states such as schizophrenia or chronic pain (11, 12), which raises the question whether there is a general framework that describes the statistics in the spatiotemporal organization of this dynamics.Recently, we found that spontaneous cortical activity in slice cultures, acute slices, and in the anesthetized rat in vivo has a scale-invariant dynamics called neuronal avalanches (13)(14)(15). These spontaneous bursts of synchronized activity occur in clusters of sizes s (where s is the number of active sites in an electrode array) that distribute according to a power law with exponent ␣:where ␣ usually lies between ...

In response to activity deprivation, CNS neurons undergo slow adaptive modification of unitary synaptic transmission. The changes are comparable in degree to those induced by brief intense stimulation, but their molecular basis is largely unknown. Our data indicate that prolonged AMPAR blockade acts through loss of Ca2+ entry through L-type Ca2+ channels to bring about an increase in both vesicle pool size and turnover rate, as well as a postsynaptic enhancement of the contribution of GluR1 homomers, concentrated at the largest synapses. The changes were consistent with a morphological scaling of overall synapse size, but also featured a dramatic shift toward synaptic drive contributed by the Ca2+-permeable homomeric GluR1 receptors. These results extend beyond "synaptic homeostasis" to involve more profound changes that can be better described as "metaplasticity".

A significant proportion of the electroencephalography (EEG) literature focuses on differences in historically pre-defined frequency bands in the power spectrum that are typically referred to as alpha, beta, gamma, theta and delta waves. Here, we review 184 EEG studies that report differences in frequency bands in the resting state condition (eyes open and closed) across a spectrum of psychiatric disorders including depression, attention deficit-hyperactivity disorder (ADHD), autism, addiction, bipolar disorder, anxiety, panic disorder, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD) and schizophrenia to determine patterns across disorders. Aggregating across all reported results we demonstrate that characteristic patterns of power change within specific frequency bands are not necessarily unique to any one disorder but show substantial overlap across disorders as well as variability within disorders. In particular, we show that the most dominant pattern of change, across several disorder types including ADHD, schizophrenia and OCD, is power increases across lower frequencies (delta and theta) and decreases across higher frequencies (alpha, beta and gamma). However, a considerable number of disorders, such as PTSD, addiction and autism show no dominant trend for spectral change in any direction. We report consistency and validation scores across the disorders and conditions showing that the dominant result across all disorders is typically only 2.2 times as likely to occur in the literature as alternate results, and typically with less than 250 study participants when summed across all studies reporting this result. Furthermore, the magnitudes of the results were infrequently reported and were typically small at between 20% and 30% and correlated weakly with symptom severity scores. Finally, we discuss the many methodological challenges and limitations relating to such frequency band analysis across the literature. These results caution any interpretation of results from studies that consider only one disorder in isolation, and for the overall potential of this approach for delivering valuable insights in the field of mental health.

No abstract

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance (R(N)), membrane time constant (tau(m)), and depolarizing "sag" in response to hyperpolarizing current pulses were similar in all subicular neurons, while R(N) and tau(m) were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.

We show that alpha and betaCaMKII are inversely regulated by activity in hippocampal neurons in culture: the alpha/beta ratio shifts toward alpha during increased activity and beta during decreased activity. The swing in ratio is approximately 5-fold and may help tune the CaMKII holoenzyme to changing intensities of Ca(2+) signaling. The regulation of CaMKII levels uses distinguishable pathways, one responsive to NMDA receptor blockade that controls alphaCaMKII alone, the other responsive to AMPA receptor blockade and involving betaCaMKII and possibly further downstream effects of betaCaMKII on alphaCaMKII. Overexpression of alphaCaMKII or betaCaMKII resulted in opposing effects on unitary synaptic strength as well as mEPSC frequency that could account in part for activity-dependent effects observed with chronic blockade of AMPA receptors. Regulation of CaMKII subunit composition may be important for both activity-dependent synaptic homeostasis and plasticity.

Across the landscape of mental health research and diagnosis, there is a diverse range of questionnaires and interviews available for use by clinicians and researchers to determine patient treatment plans or investigate internal and external etiologies. Although individually, these tools have each been assessed for their validity and reliability, there is little research examining the consistency between them in terms of what symptoms they assess, and how they assess those symptoms. Here, we provide an analysis of 126 different questionnaires and interviews commonly used to diagnose and screen for 10 different disorder types including depression, anxiety, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), addiction, bipolar disorder, eating disorder, and schizophrenia, as well as comparator questionnaires and interviews that offer an all-in-one cross-disorder assessment of mental health. We demonstrate substantial inconsistency in the inclusion and emphasis of symptoms assessed within disorders as well as considerable symptom overlap across disorder-specific tools. Within the same disorder, similarity scores across assessment tools ranged from 29% for assessment of bipolar disorder to a maximum of 58% for OCD. Furthermore, when looking across disorders, 60% of symptoms were assessed in at least half of all disorders illustrating the extensive overlap in symptom profiles between disorder-specific assessment tools. Biases in assessment toward emotional, cognitive, physical or behavioral symptoms were also observed, further adding to the heterogeneity across assessments. Analysis of other characteristics such as the time period over which symptoms were assessed, as well as whether there was a focus toward frequency, severity or duration of symptoms also varied substantially across assessment tools. The consequence of this inconsistent and heterogeneous assessment landscape is that it hinders clinical diagnosis and treatment and frustrates understanding of the social, environmental, and biological factors that contribute to mental health symptoms and disorders. Altogether, it underscores the need for standardized assessment tools that are more disorder agnostic and span the full spectrum of mental health symptoms to aid the understanding of underlying etiologies and the discovery of new treatments for psychiatric dysfunction.

No abstract