Frontoparietal correlation dynamics reveal interplay between integration and segregation during visual working memory.

Working memory requires large-scale cooperation among widespread cortical and subcortical brain regions. Importantly, these processes must achieve an appropriate balance between functional integration and segregation, which are thought to be mediated by task-dependent spatiotemporal patterns of correlated activity. Here, we used cross-correlation analysis to estimate the incidence, magnitude, and relative phase angle of temporally correlated activity from simultaneous local field potential recordings in a network of prefrontal and posterior parietal cortical areas in monkeys performing an oculomotor, delayed match-to-sample task. We found long-range intraparietal and frontoparietal correlations that display a bimodal distribution of relative phase values, centered near 0° and 180°, suggesting a possible basis for functional segregation among distributed networks. Both short- and long-range correlations display striking task-dependent transitions in strength and relative phase, indicating that cognitive events are accompanied by robust changes in the pattern of temporal coordination across the frontoparietal network.

Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia.

Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioral traits that are relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. We studied an animal model of the human 22q11 deletion syndrome, the mutation that represents the highest genetic risk of developing schizophrenia. We observed a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches was sufficient to restore wild-type-like CA1 network dynamics and hippocampal-dependent behavior during adulthood. In conclusion, our data provide insights into the network dysfunction underlying schizophrenia and highlight the use of reverse engineering to restore physiological and behavioral phenotypes in an animal model of neurodevelopmental disorder.

Sorting Overlapping Spike Waveforms from Electrode and Tetrode Recordings.

One of the outstanding problems in the sorting of neuronal spike trains is the resolution of overlapping spikes. Resolving these spikes can significantly improve a range of analyses, such as response variability, correlation, and latency. In this paper, we describe a partially automated method that is capable of resolving overlapping spikes. After constructing template waveforms for well-isolated and distinct single units, we generated pair-wise combinations of those templates at all possible time shifts from each other. Subsequently, overlapping waveforms were identified by cluster analysis, and then assigned to their respective single-unit combinations. We examined the performance of this method using simulated data from an earlier study, and found that we were able to resolve an average of 83% of the overlapping waveforms across various signal-to-noise ratios, an improvement of approximately 32% over the results reported in the earlier study. When applied to additional simulated data sets generated from single-electrode and tetrode recordings, we were able to resolve 91% of the overlapping waveforms with a false positive rate of 0.19% for single-electrode data, and 95% of the overlapping waveforms with a false positive rate of 0.27% for tetrode data. We also applied our method to electrode and tetrode data recorded from the primary visual cortex, and the results obtained for these datasets suggest that our method provides an efficient means of sorting overlapping waveforms. This method can easily be added as an extra step to commonly used spike sorting methods, such as KlustaKwik and MClust software packages, and can be applied to datasets that have already been sorted using these methods.

Effects of training on neuronal activity and interactions in primary and higher visual cortices in the alert cat.

The effects of behavioral training on early visual representations have been elusive when assessed with firing rates. Learning-induced changes in performance, however, suggest that representations should encompass early cortical stages. Here, we address the question of whether training-induced effects are pertinent to neuronal activity outside the task proper, which is a requirement if subsequent perceptional processes should profit from training. To search for a neuronal signature of training effects beyond firing rates, we measured local field potentials, multiunit and isolated spike activity during passive viewing of previously learned stimulus response associations (S+ and S-) in areas 17/18 and 21a of two alert cats. Evoked potential responses as well as gamma oscillations even during the first 200 msec were found to be stronger for S+ in both areas. Most importantly, the later parts of the response (>200 msec) not only exhibit a highly significant difference in coherent gamma oscillations for S+ and S- both within and across areas, but are also characterized by a pronounced preference in firing rate for S+ in area 21a, whereas primary cortex shows a nonsignificant trend for weaker spike responses. From these results, we conclude that training-induced plasticity occurs in adult visual cortex for behaviorally relevant stimuli by changing primarily the temporal structure of neuronal activity at early stages of cortical processing, whereas later stages of cortical processing express the increased coherence of their input in elevated firing rates.

Methods, caveats and the future of large-scale microelectrode recordings in the non-human primate.

Cognitive processes play out on massive brain-wide networks, which produce widely distributed patterns of activity. Capturing these activity patterns requires tools that are able to simultaneously measure activity from many distributed sites with high spatiotemporal resolution. Unfortunately, current techniques with adequate coverage do not provide the requisite spatiotemporal resolution. Large-scale microelectrode recording devices, with dozens to hundreds of microelectrodes capable of simultaneously recording from nearly as many cortical and subcortical areas, provide a potential way to minimize these tradeoffs. However, placing hundreds of microelectrodes into a behaving animal is a highly risky and technically challenging endeavor that has only been pursued by a few groups. Recording activity from multiple electrodes simultaneously also introduces several statistical and conceptual dilemmas, such as the multiple comparisons problem and the uncontrolled stimulus response problem. In this perspective article, we discuss some of the techniques that we, and others, have developed for collecting and analyzing large-scale data sets, and address the future of this emerging field.

NMDA lesions in the medial prefrontal cortex impair the ability to inhibit responses during reversal of a simple spatial discrimination.

Although lesion studies suggest that the rat medial prefrontal cortex (mPFc) is involved in the process necessary for reversal of a particular set of contingencies, the nature of lesion-induced deficits is unclear. The involvement of rat mPFc in reversal of a simple spatial discrimination was examined in the present study. Our hypothesis was that lesion-induced deficits may reflect a failure to inhibit a learned instrumental response. Lister Hooded rats were trained on a spatial discrimination task (SD), which required a correct barpress matching the cue location, then they were trained on reversal of SD (SDR), which required a correct barpress opposite to the cue location. Rats with mPFc lesions showed a slower learning rate compared to the controls. However, behavior of the lesioned rats during early and later reversal differed. During the initial SDR, the lesioned rats showed a greater number of barpresses during the intertrial interval and a slightly higher percent correct responses than that of the controls. Our data suggest that damage to mPFc may produce a lack of response inhibition, leading to an increase in nondiscriminated bapresses, thereby yielding a 'facilitation' during early reversal. mPFc lesion did not affect either open field activity or prepulse inhibition (PPI), a frequently used measure of sensorimotor gating. Disruption of reversal learning following damage to mPFc is partly due to a failure to inhibit instrumental responses, rather than to disruption of other processes involved in sensorimotor gating or general activity.

Performance evaluation of collision-reaction interface and internal standardization in quadrupole ICP-MS measurements.

The combined use of internal standardization with collision and reaction interface in an inductively coupled plasma quadrupole mass spectrometer (ICP-QMS-CRI) was evaluated. The behavior of several elements (Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Pb, Sb, V and Zn) was studied by introducing H(2) or He through the skimmer and sampler cones of the CRI device and by using In, Rh and Sc as internal standards. Certified reference material of trace elements in water (NIST 1643e) was used to evaluate the performance of the method. A vinegar sample and mixed food diet standard reference material were directly introduced into the equipment as complex matrices for Cr and V determinations. Improvements in accuracy and precision were attained combining both strategies. The introduction of H(2) through the skimmer cone was the best way to overcome polyatomic ions formation and to improve SBR and BEC values for several elements. The use of Sc as internal standard improved the performance of ICP-QMS-CRI.

Modulation of synchrony without changes in firing rates.

It was often reported and suggested that the synchronization of spikes can occur without changes in the firing rate. However, few theoretical studies have tested its mechanistic validity. In the present study, we investigate whether changes in synaptic weights can induce an independent modulation of synchrony while the firing rate remains constant. We study this question at the level of both single neurons and neuronal populations using network simulations of conductance based integrate-and-fire neurons. The network consists of a single layer that includes local excitatory and inhibitory recurrent connections, as well as long-range excitatory projections targeting both classes of neurons. Each neuron in the network receives external input consisting of uncorrelated Poisson spike trains. We find that increasing this external input leads to a linear increase of activity in the network, as well as an increase in the peak frequency of oscillation. In contrast, balanced changes of the synaptic weight of excitatory long-range projections for both classes of postsynaptic neurons modulate the degree of synchronization without altering the firing rate. These results demonstrate that, in a simple network, synchronization and firing rate can be modulated independently, and thus, may be used as independent coding dimensions.

Controle de qualidade físico-químico e microbiológico de soro de leite doce obtido por osmose reversa / Physical and chemical quality control and microbiological sweet whey obtained by reverse osmosis

o soro de leite é o subproduto oriundo da fermentação de derivados lácteos e apresenta elevado valor funcional e nutricional. Neste sentido, buscou-se avaliar as características físico-químicas (acidez titulável em °D, °Brix, densidade, extrato seco total, gordura total, pH, temperatura) e microbiológicas (coliforme total, coliformes termotolerantes e micro-organismos aeróbios mesófilos) em amostras (soro pasteurizado, soro armazenado, água de osmose e soro concentrado) oriundas de diferentes etapas do processamento do soro de leite doce de uma planta fundamentada em osmose reversa. Verificou- se que o soro de leite concentrado obtido apresentou estabilidade microbiológica quando imediatamente submetido à osmose inversa, além disso, as propriedades físico-químicas avaliadas atenderam aos requisitos técnicos e sanitários estabelecidos em lei. (AU)

Whey is the by-product originating from dairy fermentation and presents high nutritional and functional values. In this sense, the aim of this study was to evaluate the physicochemical [titratable acidity (ºD), Brix, density, total solids, total fat, pH, temperature] and microbiological parameters (total coliforms, thermotolerant coliforms and mesophilic aerobic microorganisms) in samples from different stages of processing sweet whey from a plant based on reverse osmosis (pasteurized whey, whey stored, reverse osmosis water and concentrated whey). In any case, it was found that the obtained concentrated whey presented microbiological stability when subjected to immediately reverse osmosis, besides the physicochemical properties values achieved the technical and sanitary requirements established by law. (AU)

Responses to natural scenes in cat V1.

Studies on processing in primary visual areas often use artificial stimuli such as bars or gratings. As a result, little is known about the properties of activity patterns for the natural stimuli processed by the visual system on a daily basis. Furthermore, in the cat, a well-studied model system for visual processing, most results are obtained from anesthetized subjects and little is known about neuronal activations in the alert animal. Addressing these issues, we measure local field potentials (lfp) and multiunit spikes in the primary visual cortex of awake cats. We compare changes in the lfp power spectra and multiunit firing rates for natural movies, movies with modified spatio-temporal correlations as well as gratings. The activity patterns elicited by drifting gratings are qualitatively and quantitatively different from those elicited by natural stimuli and this difference arises from both spatial as well as temporal properties of the stimuli. Furthermore, both local field potentials and multiunit firing rates are most sensitive to the second-order statistics of the stimuli and not to their higher-order properties. Finally, responses to natural movies show a large variability over time because of activity fluctuations induced by rapid stimulus motion. We show that these fluctuations are not dependent on the detailed spatial properties of the stimuli but depend on their temporal jitter. These fluctuations are important characteristics of visual activity under natural conditions and impose limitations on the readout of possible differences in mean activity levels.

Directed interactions between visual areas and their role in processing image structure and expectancy.

During sensory processing, cortical areas continuously exchange information in different directions along the hierarchy. The functional role of such interactions, however, has been the subject of various proposals. Here, we investigate the role of bottom-up and top-down interactions in processing stimulus structure and their relation to expected events. Applying multivariate autoregressive methods to local field potentials recorded in alert cats, we quantify directed interactions between primary (A17/18) and higher (A21) visual areas. A trial-by-trial analysis yields the following findings. To assess the role of interareal interactions in processing stimulus structure, we recorded in naïve animals during stimulation with natural movies and pink noise stimuli. The overall interactions decrease compared with baseline for both stimuli. To investigate whether forthcoming events modulate interactions, we recorded in trained animals viewing two stimuli, one of which had been associated with a reward. Several results support such modulations. First, the interactions increase compared with baseline and this increase is not observed in a context where food was not delivered. Second, these stimuli have a differential effect on top-down and bottom-up components. This difference is emphasized during the stimulus presentation and is maximal shortly before the possible reward. Furthermore, a spectral decomposition of the interactions shows that this asymmetry is most dominant in the gamma frequency range. Concluding, these results support the notion that interareal interactions are more related to an expectancy state rather than to processing of stimulus structure.