Empirical mode decomposition of local field potential data from optogenetic experiments.

Introduction: This study investigated the effects of cocaine administration and parvalbumin-type interneuron stimulation on local field potentials (LFPs) recorded in vivo from the medial prefrontal cortex (mPFC) of six mice using optogenetic tools. Methods: The local network was subject to a brief 10 ms laser pulse, and the response was recorded for 2 s over 100 trials for each of the six subjects who showed stable coupling between the mPFC and the optrode. Due to the strong non-stationary and nonlinearity of the LFP, we used the adaptive, data-driven, Empirical Mode Decomposition (EMD) method to decompose the signal into orthogonal Intrinsic Mode Functions (IMFs). Results: Through trial and error, we found that seven is the optimum number of orthogonal IMFs that overlaps with known frequency bands of brain activity. We found that the Index of Orthogonality (IO) of IMF amplitudes was close to zero. The Index of Energy Conservation (IEC) for each decomposition was close to unity, as expected for orthogonal decompositions. We found that the power density distribution vs. frequency follows a power law with an average scaling exponent of ~1.4 over the entire range of IMF frequencies 2-2,000 Hz. Discussion: The scaling exponent is slightly smaller for cocaine than the control, suggesting that neural activity avalanches under cocaine have longer life spans and sizes.

Dopamine receptor antagonists effects on low-dimensional attractors of local field potentials in optogenetic mice.

The goal of this study was to investigate the effects of acute cocaine injection or dopamine (DA) receptor antagonists on the medial prefrontal cortex (mPFC) gamma oscillations and their relationship to short term neuroadaptation that may mediate addiction. For this purpose, optogenetically evoked local field potentials (LFPs) in response to a brief 10 ms laser light pulse were recorded from 17 mice. D1-like receptor antagonist SCH 23390 or D2-like receptor antagonist sulpiride, or both, were administered either before or after cocaine. A Euclidian distance-based dendrogram classifier separated the 100 trials for each animal in disjoint clusters. When baseline and DA receptor antagonists trials were combined in a single trial, a minimum of 20% overlap occurred in some dendrogram clusters, which suggests a possible common, invariant, dynamic mechanism shared by both baseline and DA receptor antagonists data. The delay-embedding method of neural activity reconstruction was performed using the correlation time and mutual information to determine the lag/correlation time of LFPs and false nearest neighbors to determine the embedding dimension. We found that DA receptor antagonists applied before cocaine cancels out the effect of cocaine and leaves the lag time distributions at baseline values. On the other hand, cocaine applied after DA receptor antagonists shifts the lag time distributions to longer durations, i.e. increase the correlation time of LFPs. Fourier analysis showed that a reasonable accurate decomposition of the LFP data can be obtained with a relatively small (less than ten) Fourier coefficients.

Cocaine-Induced Changes in Low-Dimensional Attractors of Local Field Potentials in Optogenetic Mice.

Optogenetically evoked local field potential (LFP) recorded from the medial prefrontal cortex (mPFC) of mice during basal conditions and following a systemic cocaine administration were analyzed. Blue light stimuli were delivered to mPFC through a fiber optic every 2 s and each trial was repeated 100 times. As in the previous study, we used a surrogate data method to check that nonlinearity was present in the experimental LFPs and only used the last 1.5 s of steady activity to measure the LFPs phase resetting induced by the brief 10 ms light stimulus. We found that the steady dynamics of the mPFC in response to light stimuli could be reconstructed in a three-dimensional phase space with topologically similar "8"-shaped attractors across different animals. Therefore, cocaine did not change the complexity of the recorded nonlinear data compared to the control case. The phase space of the reconstructed attractor is determined by the LFP time series and its temporally shifted versions by a multiple of some lag time. We also compared the change in the attractor shape between cocaine-injected and control using (1) dendrogram clustering and (2) Frechet distance. We found about 20% overlap between control and cocaine trials when classified using dendrogram method, which suggest that it may be possible to describe mathematically both data sets with the same model and slightly different model parameters. We also found that the lag times are about three times shorter for cocaine trials compared to control. As a result, although the phase space trajectories for control and cocaine may look similar, their dynamics is significantly different.

Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo.

Slow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, the principal role of neurons in the emergence of this essential cognitive mechanism has not been questioned. To address the possibility of astrocytic involvement in SWA, we used a transgenic rat line expressing a calcium sensitive fluorescent protein in both astrocytes and interneurons and simultaneously imaged astrocytic and neuronal activity in vivo. Here we demonstrate, for the first time, that the astrocyte network display synchronized recurrent activity in vivo coupled to UP states measured by field recording and neuronal calcium imaging. Furthermore, we present evidence that extensive synchronization of the astrocytic network precedes the spatial build-up of neuronal synchronization. The earlier extensive recruitment of astrocytes in the synchronized activity is reinforced by the observation that neurons surrounded by active astrocytes are more likely to join SWA, suggesting causality. Further supporting this notion, we demonstrate that blockade of astrocytic gap junctional communication or inhibition of astrocytic Ca2+ transients reduces the ratio of both astrocytes and neurons involved in SWA. These in vivo findings conclusively suggest a causal role of the astrocytic syncytium in SWA generation.

Task-related modulation in the monkey inferotemporal cortex.

The latencies of the neuronal responses from the inferotemporal cortical cells were analyzed in animals performing a visual fixation task and a recognition task with the same stimulus set. A consistent reduction in response latencies of about 10 ms was observed in favor of the recognition task. It was found that behavioral relevance reduces the latency in the inferotemporal cortex and it was concluded that behavioral significance accelerates information processing. This effect has not been described previously.

Fast 3D Imaging of Spine, Dendritic, and Neuronal Assemblies in Behaving Animals.

Understanding neural computation requires methods such as 3D acousto-optical (AO) scanning that can simultaneously read out neural activity on both the somatic and dendritic scales. AO point scanning can increase measurement speed and signal-to-noise ratio (SNR) by several orders of magnitude, but high optical resolution requires long point-to-point switching time, which limits imaging capability. Here we present a novel technology, 3D DRIFT AO scanning, which can extend each scanning point to small 3D lines, surfaces, or volume elements for flexible and fast imaging of complex structures simultaneously in multiple locations. Our method was demonstrated by fast 3D recording of over 150 dendritic spines with 3D lines, over 100 somata with squares and cubes, or multiple spiny dendritic segments with surface and volume elements, including in behaving animals. Finally, a 4-fold improvement in total excitation efficiency resulted in about 500 × 500 × 650 µm scanning volume with genetically encoded calcium indicators (GECIs).

Achromatic shape processing in the inferotemporal cortex of the macaque.

The responses of single neurones in the inferior temporal cortex of awake macaque monkeys to chromatic and achromatic stimuli were investigated, with the aim of determining whether colour-independent processing occurs in this last unimodal area of the ventral visual pathway. There were no differences in the firing rate of the responses (responsiveness) or the selectivity of the inferior temporal neurons towards greyscale and coloured images. The latency of the responses was the same in the two conditions. These results stress the importance of the inferior temporal cortex in colour-independent object recognition.

Low-dimensional attractor for neural activity from local field potentials in optogenetic mice.

We used optogenetic mice to investigate possible nonlinear responses of the medial prefrontal cortex (mPFC) local network to light stimuli delivered by a 473 nm laser through a fiber optics. Every 2 s, a brief 10 ms light pulse was applied and the local field potentials (LFPs) were recorded with a 10 kHz sampling rate. The experiment was repeated 100 times and we only retained and analyzed data from six animals that showed stable and repeatable response to optical stimulations. The presence of nonlinearity in our data was checked using the null hypothesis that the data were linearly correlated in the temporal domain, but were random otherwise. For each trail, 100 surrogate data sets were generated and both time reversal asymmetry and false nearest neighbor (FNN) were used as discriminating statistics for the null hypothesis. We found that nonlinearity is present in all LFP data. The first 0.5 s of each 2 s LFP recording were dominated by the transient response of the networks. For each trial, we used the last 1.5 s of steady activity to measure the phase resetting induced by the brief 10 ms light stimulus. After correcting the LFPs for the effect of phase resetting, additional preprocessing was carried out using dendrograms to identify "similar" groups among LFP trials. We found that the steady dynamics of mPFC in response to light stimuli could be reconstructed in a three-dimensional phase space with topologically similar "8"-shaped attractors across different animals. Our results also open the possibility of designing a low-dimensional model for optical stimulation of the mPFC local network.

The interplay of holistic shape, local feature and color information in object categorization.

Although it is widely accepted that colors facilitate object and scene recognition under various circumstances, several studies found no effects of color removal in tasks requiring categorization of briefly presented animals in natural scenes. In this study, three experiments were performed to test the assumption that the discrepancy between empirical data is related to variations of the available meaningful global information such as object shapes and contextual cues. Sixty-one individuals categorized chromatic and achromatic versions of intact and scrambled images containing either cars or birds. While color removal did not affect the classification of intact stimuli, the recognition of moderately scrambled achromatic images was more difficult. This effect was accompanied by amplitude modulations of occipital event-related potentials emerging from approximately 150ms post-stimulus. Our results indicate that colors facilitate stimulus classification, but this effect becomes prominent only in cases when holistic processing is not sufficient for stimulus recognition.

Optogenetically evoked gamma oscillations are disturbed by cocaine administration.

Drugs of abuse have enormous societal impact by degrading the cognitive abilities, emotional state and social behavior of addicted individuals. Among other events involved in the addiction cycle, the study of a single exposure to cocaine, and the contribution of the effects of that event to the continuous and further use of drugs of abuse are fundamental. Gamma oscillations are thought to be important neural correlates of cognitive processing in the prefrontal cortex (PFC) which include decision making, set shifting and working memory. It follows that cocaine exposure might modulate gamma oscillations, which could result in reduced cognitive ability. Parvalbumin-positive fast-spiking interneurons play an orchestrating role in gamma oscillation induction and it has been shown recently that gamma oscillations can be induced in an anesthetized animal using optogenetic techniques. We use a knock-in mouse model together with optogenetics and in vivo electrophysiology to study the effects of acute cocaine on PFC gamma oscillation as a step toward understanding the cortical changes that may underlie continuous use of stimulants. Our results show that acute cocaine administration increases entrainment of the gamma oscillation to the optogentically induced driving frequency. Our results also suggest that this modulation of gamma oscillations is driven trough activation of D1 receptors. The acute cocaine-mediated changes in mPFC may underlie the enhancement of attention and awareness commonly reported by cocaine users and may contribute to the further use and abuse of psychostimulants.

A review on the inferior temporal cortex of the macaque.

In our review, we summarize recent advances in the research of the inferior temporal cortex (ITC) of the macaque monkey. This area of the cortex is known to have a crucial role in visual shape recognition and is regarded as being at the end stage of the so-called ventral visual pathway. In the last decade, several new findings appeared in the field without being integrated in a coherent view about the function, position, and operating principles of the area. During this decade, experimental techniques developed a great deal, and the way we look at the brain and brain function changed too. In this review, we try to integrate knowledge about the ITC to the changing view about the brain while outlining the work that has been done in the last decade.

Non-linear population firing rates and voltage sensitive dye signals in visual areas 17 and 18 to short duration stimuli.

Visual stimuli of short duration seem to persist longer after the stimulus offset than stimuli of longer duration. This visual persistence must have a physiological explanation. In ferrets exposed to stimuli of different durations we measured the relative changes in the membrane potentials with a voltage sensitive dye and the action potentials of populations of neurons in the upper layers of areas 17 and 18. For durations less than 100 ms, the timing and amplitude of the firing and membrane potentials showed several non-linear effects. The ON response became truncated, the OFF response progressively reduced, and the timing of the OFF responses progressively delayed the shorter the stimulus duration. The offset of the stimulus elicited a sudden and strong negativity in the time derivative of the dye signal. All these non-linearities could be explained by the stimulus offset inducing a sudden inhibition in layers II-III as indicated by the strongly negative time derivative of the dye signal. Despite the non-linear behavior of the layer II-III neurons the sum of the action potentials, integrated from the peak of the ON response to the peak of the OFF response, was almost linearly related to the stimulus duration.

Cortical feedback depolarization waves: a mechanism of top-down influence on early visual areas.

Despite the lack of direct evidence, it is generally believed that top-down signals are mediated by the abundant feedback connections from higher- to lower-order sensory areas. Here we provide direct evidence for a top-down mechanism. We stained the visual cortex of the ferret with a voltage-sensitive dye and presented a short-duration contrast square. This elicited an initial feedforward and lateral spreading depolarization at the square representation in areas 17 and 18. After a delay, a broad feedback wave (FBW) of neuron peak depolarization traveled from areas 21 and 19 toward areas 18 and 17. In areas 18 and 17, the FBW contributed the peak depolarization of dendrites of the neurons representing the square, after which the neurons decreased their depolarization and firing. Thereafter, the peak depolarization surrounded the figure representation over most of areas 17 and 18 representing the background. Thus, the FBW is an example of a well behaved long-range communication from higher-order visual areas to areas 18 and 17, collectively addressing very large populations of neurons representing the visual scene. Through local interaction with feedforward and lateral spreading depolarization, the FBW differentially activates neurons representing the object and neurons representing the background.