Metastable dynamics of neural circuits and networks.

Cortical neurons emit seemingly erratic trains of action potentials or "spikes," and neural network dynamics emerge from the coordinated spiking activity within neural circuits. These rich dynamics manifest themselves in a variety of patterns, which emerge spontaneously or in response to incoming activity produced by sensory inputs. In this Review, we focus on neural dynamics that is best understood as a sequence of repeated activations of a number of discrete hidden states. These transiently occupied states are termed "metastable" and have been linked to important sensory and cognitive functions. In the rodent gustatory cortex, for instance, metastable dynamics have been associated with stimulus coding, with states of expectation, and with decision making. In frontal, parietal, and motor areas of macaques, metastable activity has been related to behavioral performance, choice behavior, task difficulty, and attention. In this article, we review the experimental evidence for neural metastable dynamics together with theoretical approaches to the study of metastable activity in neural circuits. These approaches include (i) a theoretical framework based on non-equilibrium statistical physics for network dynamics; (ii) statistical approaches to extract information about metastable states from a variety of neural signals; and (iii) recent neural network approaches, informed by experimental results, to model the emergence of metastable dynamics. By discussing these topics, we aim to provide a cohesive view of how transitions between different states of activity may provide the neural underpinnings for essential functions such as perception, memory, expectation, or decision making, and more generally, how the study of metastable neural activity may advance our understanding of neural circuit function in health and disease.

Synaptic Integration of Thalamic and Limbic Inputs in Rodent Gustatory Cortex.

Neurons in the gustatory cortex (GC) process multiple aspects of a tasting experience, encoding not only the physiochemical identity of tastes, but also their anticipation and hedonic value. Information pertaining to these stimulus features is relayed to GC via the gustatory thalamus (VPMpc) and basolateral amygdala (BLA). It is not known whether these inputs drive separate groups of neurons, thus activating separate channels of information, or are integrated by neurons that receive both afferents. Here, we used anterograde labeling and in vivo intracellular recordings in anesthetized rats to assess the potential convergence of BLA and VPMpc inputs in GC, and to investigate the dynamics of integration of these inputs. We report substantial anatomic overlap of BLA and VPMpc axonal fields across GC, and identify a population of GC neurons receiving converging BLA and VPMpc inputs. Our data show that BLA modulates the gain of VPMpc-evoked responses in a time-dependent fashion and that this modulation is dependent on the recruitment of synaptic inhibition by both BLA and VPMpc. Our results suggest that BLA shapes cortical processing of thalamic inputs by dynamically gating the excitatory/inhibitory balance of the GC circuit.

Taxono-genomics and description of Gordonibacter massiliensis sp. nov., a new bacterium isolated from stool of healthy patient.

Using the taxono-genomics concept, we describe here a strictly anaerobic Gram-positive bacillus. This strain was isolated from the stool sample of a 50-year-old healthy Bedouin woman. The 16S rRNA gene sequence analysis and the whole-genome sequencing showed that this isolate belonged to the genus Gordonibacter in the family Eggerthellaceae. Based on these criteria, we propose the creation of Gordonibacter massiliensis sp. nov., strain Marseille-P2775T (= CSUR P2775).

Taxono-genomics and description of Haloimpatiens massiliensis sp. nov., a new bacterium isolated from the gut of a healthy infant.

A polyphasic taxono-genomic strategy was used to describe a new bacterium, strain Marseille-P1935; isolated from the gut of a healthy infant. 16S rRNA sequencing showed that the isolate belongs to the genus Haloimpatiens in the family Clostridiaceae. Phenotypic analysis and whole-genome sequence analyses confirm the status of the new species. We propose the creation of the new species Haloimpatiens massiliensis strain Marseille-P1935T (= CSURP1935T; = DSM100591T).

Genome sequence and description of Urinicoccus timonensis gen. nov., sp. nov., a new bacterium isolated from a human stool sample.

Urinicoccus timonensis gen. nov., sp. nov. strain Marseille-P3926T is a new species from the phylum Firmicutes and the family Peptoniphilaceae that was isolated from a human faeces sample. Genome was 1 978 908 bp long with a 41.1 G + C content. The closest species based on 16S ribosomal RNA was Peptoniphilus ivorii DSM 10022 with 90.8% sequence similarity. Considering phenotypic features, 16S rRNA sequence and comparative genome studies, we proposed Marseille- P3926T as the strain type of Urinicoccus timonensis gen. nov., sp. nov.

Expectation-induced modulation of metastable activity underlies faster coding of sensory stimuli.

Sensory stimuli can be recognized more rapidly when they are expected. This phenomenon depends on expectation affecting the cortical processing of sensory information. However, the mechanisms responsible for the effects of expectation on sensory circuits remain elusive. In the present study, we report a novel computational mechanism underlying the expectation-dependent acceleration of coding observed in the gustatory cortex of alert rats. We use a recurrent spiking network model with a clustered architecture capturing essential features of cortical activity, such as its intrinsically generated metastable dynamics. Relying on network theory and computer simulations, we propose that expectation exerts its function by modulating the intrinsically generated dynamics preceding taste delivery. Our model's predictions were confirmed in the experimental data, demonstrating how the modulation of ongoing activity can shape sensory coding. Altogether, these results provide a biologically plausible theory of expectation and ascribe an alternative functional role to intrinsically generated, metastable activity.

Acidaminococcus provencensis sp. nov., a new bacterium isolated from a fresh human stool specimen.

Acidaminococcus provencensis strain Marseille-P4266T (= CSURP4266T) is a new species isolated from a fresh human stool specimen.

Enterobacter timonensis sp. nov., a new bacterium isolated from a fresh human stool specimen.

Enterobacter timonensis strain mt20T (= CSUR P2201T, = DSM101775T) is a new species isolated from a fresh human stool specimen.

Prevotella ihumii sp. nov., a new bacterium isolated from a stool specimen of a healthy woman.

Prevotella ihumii strain Marseille-P3385T (= CSURP3385T; = DSM106428T) is a new species isolated from a fresh stool specimen of a healthy woman.

Virgibacillus ndiopensis sp. nov., a new halophilic bacterium isolated from the stool of a healthy 11-year-old boy.

Virgibacillus ndiopensis strain Marseille-P3835T (= CSURP3835T; = CCUG70388T) is a new specie isolated from the stool of a healthy 11-year-old boy from N'Diop, Senegal.

Clostridium pacaense: a new species within the genus Clostridium.

Using the strategy of taxonogenomics, we described Clostridium pacaense sp. nov. strain Marseille-P3100T, a Gram-variable, nonmotile, spore-forming anaerobic bacillus. This strain was isolated from a 3.3-month-old Senegalese girl with clinical aspects of marasmus. The closest species based on 16S ribosomal RNA was Clostridium aldenense, with a similarity of 98.4%. The genome length was 2 672 129 bp, with a 50% GC content; 2360 proteins were predicted. Finally, predominant fatty acids were hexadecanoic acid, tetradecanoic acid and 9-hexadecenoic acid.

Caspase activation and apoptosis in response to proteasome inhibitors.

Several studies have indicated that proteasome inhibitors (PIs) are promising anticancer agents. We have discovered that PIs have the unique ability to activate effector caspases through a mitochondrial Bcl-2 inhibitable but caspase-9 independent pathway. Stabilization of released Smac induced by blockade of the proteasome could explain the apoptosome-independent cell death induced by PIs. In fact, Smac/DIABLO critically supports this PIs-dependent caspase activation. By using a new assay, we confirm that at a single cell level both Smac and PIs can activate caspases in the absence of the apoptosome. Moreover, we have observed two PIs-induced kinetics of caspase activation, with caspase-9 being still required for the rapid caspase activation in response to mitochondrial depolarization, but dispensable for the slow DEVDase activation. In summary, our data indicate that PIs can activate downstream caspases at least in part through Smac/DIABLO stabilization.