Growing animal data evince a critical role of the sensory cortex in the long-term storage of aversive conditioning, following acquisition and consolidation in the amygdala. Whether and how this function is conserved in the human sensory cortex is nonetheless unclear. We interrogated this question in a human aversive conditioning study using multidimensional assessments of conditioning and long-term (15 d) retention. Conditioned stimuli (CSs; Gabor patches) were calibrated to differentially activate the parvocellular (P) and magnocellular (M) visual pathways, further elucidating cortical versus subcortical mechanisms. Full-blown conditioning and long-term retention emerged for M-biased CS (vs limited effects for P-biased CS), especially among anxious individuals, in all four dimensions assessed: threat appraisal (threat ratings), physiological arousal (skin conductance response), perceptual learning [discrimination sensitivity ( d ′) and response speed], and cortical plasticity [visual evoked potentials (VE...

Seeing a speaker’s face benefits speech comprehension, especially in challenging listening conditions. This perceptual benefit is thought to stem from the neural integration of visual and auditory speech at multiple stages of processing, whereby movement of a speaker’s face provides temporal cues to auditory cortex, and articulatory information from the speaker’s mouth can aid recognizing specific linguistic units (e.g., phonemes, syllables). However it remains unclear how the integration of these cues varies as a function of listening conditions. Here we sought to provide insight on these questions by examining EEG responses in humans (males and females) to natural audiovisual, audio, and visual speech in quiet and in noise. We represented our speech stimuli in terms of their spectrograms and their phonetic features, and then quantified the strength of the encoding of those features in the EEG using canonical correlation analysis. The encoding of both spectrotemporal and phonetic features was shown to be ...

Transmembrane channel-like protein isoform 1 (TMC1) is a major component of the mechano-electrical transducer (MET) channel in cochlear hair cells and is subject to numerous mutations causing deafness. We report a new dominant human deafness mutation, TMC1 p.T422K, and have characterized the homologous mouse mutant, Tmc1 p.T416K, which caused deafness and outer hair cell loss by the fourth postnatal week. MET channels showed decreased Ca2+ permeability and resting open probability, but no change in single-channel conductance or expression. Three adjacent deafness mutations are TMC1 p.L416R, p.G417R and p.M418K, the last homologous to the mouse Beethoven that exhibits similar channel effects. All substitute a positive for a neutral residue, which could produce charge screening in the channel pore or influence binding of an accessory subunit. Channel properties were compared in mice of both sexes between dominant ( Tmc1 p.T416K, Tmc1 p.D569N) and recessive ( Tmc1 p.W554L, Tmc1 p.D528N) mutations of residues ...

Release of neuropeptides from dense core vesicles (DCVs) is essential for neuromodulation. Compared to the release of small neurotransmitters, much less is known about the mechanisms and proteins contributing to neuropeptide release. By optogenetics, behavioral analysis, electrophysiology, electron microscopy, and live imaging, we show that synapsin SNN-1 is required for cAMP-dependent neuropeptide release in Caenorhabditis elegans hermaphrodite cholinergic motor neurons. In synapsin mutants, behaviors induced by the photoactivated adenylyl cyclase bPAC, which we previously showed to depend on acetylcholine and neuropeptides (Steuer Costa et al., 2017), are altered like in animals with reduced cAMP. Synapsin mutants have slight alterations in synaptic vesicle (SV) distribution, however, a defect in SV mobilization was apparent after channelrhodopsin-based photostimulation. DCVs were largely affected in snn-1 mutants: DCVs were ∼30% reduced in synaptic terminals, and not released following bPAC stimulation....

Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been largely overlooked. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly controlled variables. Genetically engineered mouse models are widely used to gain insight into the biology of human NDDs, but research focus has been on behavioral and neurophysiological abnormalities. Such models not only allow for evaluating usefulness in reproducing human features, including similarities and discrepancies with rodent phenotypes, but they also represent a unique opportunity to observe and quantify novel anomalies. Here, we present the first characterization and comparison of basal metabolism in three mouse models of NDDs, namely Down syndrome ( Dp(16)Yey/+ mice), 16p11.2 deletion syndrome ( 16p11.2df/+ mice) and Fragile X syndrome ( Fmr1 KO mice) and their wild-type counterparts. Using the Compre...

Cell movement propels embryonic tissues to acquire shapes required for mature function. The movements are driven both by acto-myosin signaling, and by cells interacting with the extracellular matrix. Unknown is whether cell-cell interactions within a tissue are also required, and the molecular mechanisms by which such communication might occur. Here we use the developing visual system of zebrafish as a model to understand the role cell-cell communication plays in tissue morphogenesis in the embryonic nervous system. We identify that cell-cell mediated contact between two distinct cell populations, progenitors of the neural retina and retinal pigment epithelium, facilitates epithelial flow to produce the mature cupped retina. We identify for the first time the need in eye morphogenesis for distinct populations of progenitors to interact, and suggest a novel role for a member of a key developmental signaling family, the transmembrane Semaphorin6d, as mediating communication between distinct cell types to con...

The objective of this review of the literature is to summarize the physiology of orofacial pain in dentistry, particularly physiology of the pain pathway and molecular mechanisms on pathophysiology of pain, on account of new insights into classification of orofacial pain related diseases. This article will also focus on possible mechanisms of neuropathic orofacial pain which is distinguished from other pain types.

The human brain continuously processes streams of visual input. Yet, a single image typically triggers neural responses that extend beyond one second. To understand how the brain encodes and maintains successive images, we analyzed with electro-encephalography the brain activity of human subjects of either sex, while they watched ∼5,000 visual stimuli presented within fast sequences. First, we confirm that each stimulus can be decoded from brain activity for ∼1 sec, and demonstrate that the brain simultaneously represents multiple images at each time instant. Second, we source-localize the corresponding brain responses in the expected visual hierarchy, and show that distinct brain regions represent different snapshots of past stimulations. Third, we propose a simple framework to further characterize the dynamical system of these traveling waves. Our results show that a chain of neural circuits, which consist of (i) a hidden maintenance mechanism, and (ii) an observable update mechanism, accounts for the dy...

Stability and precision of sequential activity in the entorhinal cortex is crucial for encoding spatially guided behavior and memory. These sequences are driven by constantly evolving sensory inputs and persist despite a noisy background. In a realistic computational model of a medial entorhinal cortex (MEC) microcircuit, we show that intrinsic neuronal properties and network mechanisms interact with theta oscillations to generate reliable outputs. In our model, sensory inputs activate interneurons near their most excitable phase during each theta cycle. As the inputs change, different interneurons are recruited and postsynaptic stellate cells are released from inhibition. This causes a sequence of rebound spikes. The rebound time scale of stellate cells, due to an h –current, matches that of theta oscillations. This fortuitous similarity of time-scales ensures that stellate spikes get relegated to the least excitable phase of theta and the network encodes the external drive but ignores recurrent excitatio...

Numerous studies have proposed that specific brain activity statistics provide evidence that the brain operates at a critical point, which could have implications for the brain’s information processing capabilities. A recent paper reported that identical scalings and criticality signatures arise in a variety of different neural systems (neural cultures, cortical slices, anesthetized or awake brains, across both reptiles and mammals). The diversity of these states calls into question the claimed role of criticality in information processing. We analyze the methodology used to assess criticality and replicate this analysis for spike trains of two non-critical systems. These two non-critical systems pass all the tests used to assess criticality in the aforementioned recent paper. This analysis provides a crucial control (which is absent from the original study) and suggests that the methodology used may not be sufficient to establish that a system operates at criticality. Hence whether the brain operates at c...