Parker J. Ellingson, William H. Barnett, Daniel Kueh, Alex Vargas, Ronald L. Calabrese, et al. (see pages [6468–6483][1]) Rhythmic behaviors such as chewing and walking are driven by neural circuits called central pattern generators (CPGs), which generate rhythmic output through a combination of

Critical decisions, such as in domains ranging from medicine to finance, are often made under threatening circumstances that elicit stress and anxiety. The negative effects of such reactions on learning and decision-making have been repeatedly underscored. In contrast, here we show that perceived threat alters the process by which evidence is accumulated in a way that may be adaptive. Participants ( n = 91) completed a sequential evidence sampling task in which they were incentivized to accurately judge whether they were in a desirable state, which was associated with greater rewards than losses, or an undesirable state, which was associated with greater losses than rewards. Before the task participants in the “threat group” experienced a social-threat manipulation. Results show that perceived threat led to a reduction in the strength of evidence required to reach an undesirable judgment. Computational modeling revealed this was because of an increase in the relative rate by which negative information was ...

Central pattern generators (CPGs), specialized oscillatory neuronal networks controlling rhythmic motor behaviors such as breathing and locomotion, must adjust their patterns of activity to a variable environment and changing behavioral goals. Neuromodulation adjusts these patterns by orchestrating changes in multiple ionic currents. In the medicinal leech, the endogenous neuromodulator myomodulin speeds up the heartbeat CPG by reducing the electrogenic Na+/K+ pump current and increasing h-current in pairs of mutually inhibitory leech heart interneurons (HNs), which form half-center oscillators (HN HCOs). Here we investigate whether the comodulation of two currents could have advantages over a single current in the control of functional bursting patterns of a CPG. We use a conductance-based biophysical model of an HN HCO to explain the experimental effects of myomodulin. We demonstrate that, in the model, comodulation of the Na+/K+ pump current and h-current expands the range of functional bursting activit...

The adaptable transcriptional response to changes in food availability not only ensures animal survival but also lets embryonic development progress. Interestingly, the CNS is preferentially protected from periods of malnutrition, a phenomenon known as “brain sparing.” However, the mechanisms that mediate this response remain poorly understood. To get a better understanding of this, we used Drosophila melanogaster as a model, analyzing the transcriptional response of neural stem cells (neuroblasts) and glia of the blood–brain barrier (BBB) from larvae of both sexes during nutrient restriction using targeted DamID. We found differentially expressed genes in both neuroblasts and glia of the BBB, although the effect of nutrient deficiency was primarily observed in the BBB. We characterized the function of a nutritional sensitive gene expressed in the BBB, the serine protease homolog, scarface ( scaf ). Scaf is expressed in subperineurial glia in the BBB in response to nutrition. Tissue-specific knockdown of s...

N -methyl-d-aspartate receptors (NMDARs) are important for synaptic plasticity associated with many physiological functions and neurologic disorders. Protein kinase C (PKC) activation increases the phosphorylation and activity of NMDARs, and α2δ-1 is a critical NMDAR-interacting protein and controls synaptic trafficking of NMDARs. In this study, we determined the relative roles of PKC and α2δ-1 in the control of NMDAR activity. We found that α2δ-1 coexpression significantly increased NMDAR activity in HEK293 cells transfected with GluN1/GluN2A or GluN1/GluN2B. PKC activation with phorbol 12-myristate 13-acetate (PMA) increased receptor activity only in cells coexpressing GluN1/GluN2A and α2δ-1. Remarkably, PKC inhibition with Gӧ6983 abolished α2δ-1-coexpression-induced potentiation of NMDAR activity in cells transfected with GluN1/GluN2A or GluN1/GluN2B. Treatment with PMA increased the α2δ-1–GluN1 interaction and promoted α2δ-1 and GluN1 cell surface trafficking. PMA also significantly increased NMDAR act...

Although composing two words into a complex representation (e.g., “coffee cake”) is conceptually different from forming associations between a pair of words (e.g., “coffee, cake”), the brain regions supporting semantic composition have also been implicated for associative encoding. Here, we adopted a two-word magnetoencephalography (MEG) paradigm which varies compositionality (“French/Korean cheese” vs “France/Korea cheese”) and strength of association (“France/French cheese” vs “Korea/Korean cheese”) between the two words. We collected MEG data while 42 English speakers (24 females) viewed the two words successively in the scanner, and we applied both univariate regression analyses and multivariate pattern classification to the source estimates of the two words. We show that the left anterior temporal lobe (LATL) and left middle temporal lobe (LMTL) are distinctively modulated by semantic composition and semantic association. Specifically, the LATL is mostly sensitive to high-association compositional phr...

Current models of object recognition are based on spatial representations build from object features that are simultaneously present in the retinal image. However, one can recognize an object when it moves behind a static occlude, and only a small fragment of its shape is visible through a slit at a given moment in time. Such anorthoscopic perception requires spatiotemporal integration of the successively presented shape parts during slit-viewing. Human fMRI studies suggested that ventral visual stream areas represent whole shapes formed through temporal integration during anorthoscopic perception. To examine the time course of shape-selective responses during slit-viewing, we recorded the responses of single inferior temporal (IT) neurons of rhesus monkeys to moving shapes that were only partially visible through a static narrow slit. The IT neurons signaled shape identity by their response when that was cumulated across the duration of the shape presentation. Their shape preference during slit-viewing eq...

Peptide neuromodulation has been implicated to shield neuronal activity from acute temperature changes which can otherwise lead to loss of motor control or failure of vital behaviors. However, the cellular actions neuropeptides elicit to support temperature-robust activity remain unknown. Here, we uncover that peptide neuromodulation restores rhythmic bursting in temperature-compromised central pattern generator (CPG) neurons by counteracting membrane shunt and increasing dendritic electrical spread. We show that acutely rising temperatures reduced spike generation and interrupted ongoing rhythmic motor activity in the crustacean gastric mill CPG. Neuronal release and extrinsic application of Cancer borealis tachykinin-related peptide Ia (CabTRP Ia), a substance P-related peptide, restored rhythmic activity. Warming led to a significant decrease in membrane resistance and a shunting of the dendritic signals in the main gastric mill CPG neuron. Using a combination of fluorescent Calcium imaging and electro...

The spatial organization and dynamic interactions between excitatory and inhibitory synaptic inputs that define the receptive field (RF) of simple cells in cat primary visual cortex (V1) still raise paradoxical issues: 1) stimulation of simple cells in V1 with drifting gratings supports a wiring schema of spatially segregated sets of excitatory and inhibitory inputs activated in an opponent way by stimulus contrast polarity; 2) in contrast, intracellular studies using flashed bars suggest that, while ON and OFF excitatory input are indeed segregated, inhibitory inputs span the entire RF irrespective of input contrast polarity. Here, we propose a biologically detailed computational model of simple cells embedded in a V1-like network that resolves this seeming contradiction. We varied parametrically the RF-correlation-based bias for excitatory and inhibitory synapses and found that a moderate bias of excitatory neurons to synapse onto other neurons with correlated receptive fields, and a weaker bias of inhib...