Rhythmically active networks are typically composed of neurons that can be classified as silent, tonic spiking, or rhythmic bursting based on their intrinsic activity patterns. Within these networks, neurons are thought to discharge in distinct phase relationships with their overall network output, and it has been hypothesized that bursting pacemaker neurons may lead and potentially trigger cycle onsets. We used multielectrode recording from 72 experiments to test these ideas in rhythmically active slices containing the pre-Bötzinger complex, a region critical for breathing. Following synaptic blockade, respiratory neurons exhibited a gradient of intrinsic spiking to rhythmic bursting activities and thus defied an easy classification into bursting pacemaker and nonbursting categories. Features of their firing activity within the functional network were analyzed for correlation with subsequent rhythmic bursting in synaptic isolation. Higher firing rates through all phases of fictive respiration statistically predicted bursting pacemaker behavior. However, a cycle-by-cycle analysis indicated that respiratory neurons were stochastically activated with each burst. Intrinsically bursting pacemakers led some population bursts and followed others. This variability was not reproduced in traditional fully interconnected computational models, while sparsely connected network models reproduced these results both qualitatively and quantitatively. We hypothesize that pacemaker neurons do not act as clock-like drivers of the respiratory rhythm but rather play a flexible and dynamic role in the initiation and stabilization of each burst. Thus, at the behavioral level, each breath can be thought of as de novo assembly of a stochastic collaboration of network topology and intrinsic properties.

A direct-current current-voltage (DCIV) measurement technique of interface and oxide traps on oxidized silicon is demonstrated. It uses the gate-controlled parasitic bipolar junction transistor of a metal-oxide-silicon field-effect transistor in a pln junction isolation well to monitor the change of the oxide and interface trap density. The dc base and collector currents are the monitors, hence, this technique is more sensitive and reliable than the traditional ac methods for determination of fundamental kinetic rates and transistor degradation mechanisms, such as charge pumping.

Carroll MS, Viemari JC, Ramirez JM. Patterns of inspiratory phase-dependent activity in the in vitro respiratory network. J Neurophysiol 109: 285-295, 2013. First published October 17, 2012 doi:10.1152/jn.00619.2012.-Mechanistic descriptions of rhythmogenic neural networks have often relied on ball-and-stick diagrams, which define interactions between functional classes of cells assumed to be reasonably homogenous. Application of this formalism to networks underlying respiratory rhythm generation in mammals has produced increasingly intricate models that have generated significant insight, but the underlying assumption that individual cells within these network fall into distinct functional classes has not been rigorously tested. In the present study we used multiunit extracellular recording in the in vitro pre-Bötzinger complex to identify and characterize the rhythmic activity of 951 cells. Inspiratory phasedependent activity was estimated for all cells, and the data set as a whole was analyzed with principal component analysis, nonlinear dimensionality reduction, and hierarchical clustering techniques. None of these techniques revealed categorically distinct functional cell classes, indicating instead that the behavior of these cells within the network falls along several continua of spiking behavior. neuronal networks; pre-Bötzinger complex; respiration; cell types RHYTHMIC ACTIVITY IS UBIQUITOUS in neural systems, from the slow rhythm generated by the suprachiasmatic nuclei that synchronizes mammalian circadian cycles (Dibner et al. 2010), to the broad frequency spectra covered by various oscillations generated within cortical networks (Buzsaki and Draguhn 2004;Tort et al. 2010;Wang 2010). Many of the underlying rules of rhythm generation have been established in neural circuits that generate rhythmic motor behaviors (Goulding 2009;Grillner 2006;Marder and Calabrese 1996). These motor activities are typically reciprocal in nature (e.g., expiration and inspiration, extension and flexion, protraction and retraction) and are often described by ball-and-stick 1 schematics that assume specific connectivity (sticks) between different types of cells or cell populations (balls). In these models each cell possesses functionally discrete properties firing in distinct phases with respect to a given global activity pattern (Guertin 2009; Selverston 2010). Ball-and-stick representations have been particularly powerful in invertebrate neuronal networks (Antonsen and Edwards 2003), because the firing and connectivity properties of physiologically and anatomically identified individual neurons could be reproducibly characterized across different individuals of the same species (Jing et al. 2010;Katz et al. 2010;Marder and Calabrese 1996;Newcomb et al. 2012; Ramirez, 1998;White and Nusbaum 2011). One of the many important lessons learned from these small invertebrate networks is that even in the case of a truly identified neuron, electrophysiological measures of single-cell properties do not suffice to uniquely specify a ...

Traumatic brain injury (TBI)is a major cause of epilepsy, yet the mechanisms underlying the progression from TBI to epilepsy are unknown. TBI induces the expression of COX-2 (cyclooxygenase-2) and increases levels of prostaglandin E2 (PGE2). Here, we demonstrate that acutely applied PGE2 (2 M) decreases neocortical network activity by postsynaptically reducing excitatory synaptic transmission in acute and organotypic neocortical slices of mice. In contrast, long-term exposure to PGE2 (2 M; 48 h) presynaptically increases excitatory synaptic transmission, leading to a hyperexcitable network state that is characterized by the generation of paroxysmal depolarization shifts (PDSs). PDSs were also evoked as a result of depriving organotypic slices of activity by treating them with tetrodotoxin (TTX, 1 M; 48 h). This treatment predominantly increased postsynaptically excitatory synaptic transmission. The network and cellular effects of PGE2 and TTX treatments reversed within 1 week. Differences in the underlying mechanisms (presynaptic vs postsynaptic) as well as occlusion experiments in which slices were exposed to TTX plus PGE2 suggest that the two substances evoke distinct forms of homeostatic plasticity, both of which result in a hyperexcitable network state.PGE2 and TTX (alone or together with PGE2) also increased levels of apoptotic cell death in organotypic slices. Thus, we hypothesize that the increase in excitability and apoptosis may constitute the first steps in a cascade of events that eventually lead to epileptogenesis triggered by TBI.

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