Denial of Reward in the Neonate Shapes Sociability and Serotonergic Activity in the Adult Rat

BACKGROUND: Manipulations of the early environment are linked to long-lasting alterations of emotionality and social capabilities. Denial of rewarding mother-pup interactions in early life of rats could serve as model for child neglect. Negative consequences for social competence in later life, accompanied by changes in the serotonergic system would be expected. In contrast, rewarding mother-pup contact should promote adequate social abilities. METHODOLOGY/PRINCIPAL FINDINGS: Male Wistar rats trained in a T-maze during postnatal days 10-13 under denial (DER) or permission (RER) of maternal contact were tested for play behavior in adolescence and for coping with defeat in adulthood. We estimated serotonin (5-HT) levels in the brain under basal conditions and following defeat, as well as serotonin receptor 1A (5-HT1A) and serotonin transporter (SERT) expression. DER rats exhibited increased aggressive-like play behavior in adolescence (i.e. increased nape attacks, p<0.0001) and selected a proactive coping style during defeat in adulthood (higher sum of proactive behaviors: number of attacks, flights, rearings and defensive upright posture; p = 0.011, p<0.05 vs RER, non-handled-NH). In adulthood, they had lower 5-HT levels in both the prefrontal cortex (p<0.05 vs RER) and the amygdala (p<0.05 vs NH), increased 5-HT levels following defeat (PFC p<0.0001) and decreased serotonin turnover (amygdala p = 0.008). The number of 5-HT1A immunopositive cells in the CA1 hippocampal area was increased (p<0.05 DER, vs RER, NH); SERT levels in the amygdala were elevated (p<0.05 vs RER, NH), but were lower in the prefrontal cortex (p<0.05 vs NH). CONCLUSIONS/SIGNIFICANCE: Denial of expected maternal reward early in life negatively affects sociability and the serotonergic system in a complex manner. We propose that our animal model could contribute to the identification of the neurobiological correlates of early neglect effects on social behavior and coping with challenges, but also in parallel with the effects of a rewarding early-life environment

Neural mechanisms of conscious visual perception in the prefrontal cortex: From single units to correlations and spatiotemporal patterns

Until recently the temporal cortex was the only known area where neuronal discharges during subjective visual perception closely matched the respective activity during perception without a subjective component, indicating a robust representation of the content of visual awareness. However, it was not clear whether conscious perception should be uniquely localized in the temporal association cortex. We focused on the next level of the ventral visual stream, the ventrolateral prefrontal cortex (PFC), and found single units that also represent reliably conscious content, suggesting a frontotemporal cortical workspace of conscious access. We also studied whether emergent properties of functional connectivity patterns like the structure of interneuronal firing correlations in the PFC could constrain the population coding accuracy and found a non-detrimental correlation structure during subjective perception. These empirical findings are used to constrain biophysically realistic models in an effort to pin down the dynamic mechanisms of perceptual stability and spontaneous perceptual transitions. The latter could be ascribed to spontaneous fluctuations of intrinsic activity that induce perceptual reorganization. In order to gain a preliminary understanding of these fluctuations in the PFC we used multielectrode (Utah array) recordings and mapped the dynamic spatiotemporal structure of oscillatory activity revealing a dominant travelling wave pattern in the beta (15-30Hz) frequency band

Spatiotemporal patterns of sub-threshold oscillatory activity in the inferior convexity of the macaque prefrontal cortex

Despite significant progress in understanding functional parcellation of the primate prefrontal cortex (PFC) it is currently unknown whether an intrinsic mechanism could dynamically coordinate activity between these functionally specialized sub-regions. Such a mechanism could be reflected in spatially organized rhythmic activity that is mesoscopically observed as complex, rhythmic spatio-temporal patterns. In order to identify such spatio-temporal patterns in the default state of the prefrontal cortical network we recorded from the inferior convexity of the macaque PFC during anesthesia using multi-electrode (Utah) arrays. The power spectrum and spatial coherence of oscillatory activity exhibited a distinctive peak in the beta (15-30 Hz) frequency range of local field potentials (LFP's) during resting state but also during sensory stimulation with dynamic movie stimuli, revealing a dominant rhythm in the PFC. We observed consistent phase gradients in the beta band that formed complex, dynamic patterns, suggesting propagation of oscillatory activity across the cortical surface. These spatio-temporal patterns were subsequently clustered using a graph cut algorithm based on a measure of phase shift invariant similarity. Our analysis revealed a dominant travelling wave pattern in the beta band, propagating along the ventral-dorsal plane and replaced by less frequent, less dominant patterns both in the absence of visual stimulation (spontaneous activity) and during stimulation with movie clips. By estimating mutual information, we found that the amplitude of this wave conveyed sensory information during the presentation of several movies. These findings suggest that spatiotemporal phenomena are suggestive of highly coordinated activity in the PFC, a cortical area known to be involved in associative functions. In particular, traveling waves of oscillatory neural activity are modulated by sensory input and could provide a functional substrate for coordinating activity across different subregions of the PFC

Beta oscillations propagate as traveling waves in the macaque prefrontal cortex

Despite significant progress in understanding functional parcellation of the primate prefrontal cortex (PFC) it is currently unknown whether an intrinsic mechanism could dynamically coordinate activity between these functionally specialized sub-regions. Such a mechanism could be reflected in spatially organized rhythmic activity that is macroscopically observed as complex, rhythmic spatio-temporal patterns. Here, we used multielectrode arrays (Utah arrays) and recorded neural activity from a large area (16mm2) of the macaque lateral PFC during anesthesia in order to explore spatio-temporal patterns in the default state of the prefrontal cortical network. We recorded local field potentials (LFP's) (1-200Hz) and found that the spatial coherence of oscillatory activity exhibited a distinctive peak in the "beta" (15-30 Hz) frequency range during resting state but also during visual stimulation with dynamic movie stimuli. We then used the Hilbert transform to obtain the analytic signal and evaluated the two-dimensional instantaneous phase maps. We observed consistent phase gradients in the "beta" frequency range that formed complex, dynamic patterns, suggesting propagation of oscillatory activity across the cortical surface. A graph cut algorithm based on a measure of phase shift invariant similarity was used to cluster these spatio-temporal patterns. Our analysis revealed a dominant travelling wave pattern in the "beta" band, propagating along the ventral-dorsal plane and replaced by less frequent, less dominant patterns both in the absence of visual stimulation (spontaneous activity) and during stimulation with movie clips. By estimating mutual information, we found that the amplitude of this wave conveyed sensory information during the presentation of several movies. Our data show that travelling wave phenomena are suggestive of highly coordinated activity in the PFC, a cortical area known to be involved in higher order sensory processing. These traveling waves of oscillatory neural activity are modulated by sensory input and could provide a functional substrate for coordinating activity across different subregions of the PFC. Finally, our approach enables the unsupervised analysis of the complex spatio-temporal neural dynamics in ongoing oscillatory signals, providing an analytical framework to understand cooperative mechanisms in spatially distributed neural populations

Subjective visual perception: From local processing to emergent phenomena of brain activity

The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness