Neurobehavioral studies in humans have long concentrated on changes in local activity levels during repetitive executions of a task. Spontaneous neural coupling within extended networks has latterly been found to also influence performance. Here, we intend to uncover the underlying mechanisms, the relative importance, and the interaction between spontaneous coupling and task-induced activations. To do so, we recorded two groups of healthy participants (male and female) during rest and while they performed either a visual perception or a motor sequence task. We demonstrate that, for both tasks, stronger activations during the task as well as greater network coupling through spontaneous α rhythms at rest predict performance. However, high performers present an absence of classical task-induced activations and, instead, stronger spontaneous network coupling. Activations were thus a compensation mechanism needed only in subjects with lower spontaneous network interactions. This challenges classical models of n...

Selective visual attention allows the brain to focus on behaviorally relevant information while ignoring irrelevant signals. As a possible mechanism, routing-by-synchronization was proposed: neural populations receiving attended signals align their gamma-rhythmic activity to that of the sending populations, such that incoming spikes arrive at excitability peaks of receiving populations, enhancing signal transfer. Conversely, non-attended signals arrive unaligned to the receiver's oscillation, reducing signal transfer. Therefore, visual signals should be transferred through gamma-rhythmic bursts of information, resulting in a modulation of the stimulus content within the receiving population's activity by its gamma phase and amplitude. To test this prediction, we quantified gamma-phase-dependent stimulus content within neural activity from area V4 of two male macaques performing a visual attention task. For the attended stimulus, we find highest stimulus information content near excitability peaks, an effec...

Invited reviewers are asked to identify colleagues who assisted with review. JNeurosci would like to acknowledge the hard work of these collaborating reviewers and thank them for their service to the journal. Sarah Ackerman Chinnakkaruppan Adaikkan Anisha Adke Kadidia Adula Jayne Aiken Lucas

d-serine is the primary NMDAR coagonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR). However, our understanding of the mechanisms regulating the availability of synaptic d-serine remains limited. Though early studies suggested d-serine is synthesized and released from astrocytes, more recent studies have demonstrated a predominantly neuronal localization of SR. More specifically, recent work intriguingly suggests that SR may be found at the postsynaptic density, yet the functional implications of postsynaptic SR on synaptic transmission are not yet known. Here, we show an age-dependent dendritic and postsynaptic localization of SR and d-serine by immunohistochemistry and electron microscopy in mouse CA1 pyramidal neurons. In addition, using a single-neuron genetic approach in SR conditional KO mice from both sexes, we demonstrate a cell-autonomous role for SR in regulating synaptic NMDAR function at Schaffer collateral (CA3)-CA1 synapses. Importantly, single-neuron ge...

Itch can be induced by activation of small-diameter DRG neurons, which express abundant intracellular fibroblast growth factor 13 (FGF13). Although FGF13 is revealed to be essential for heat nociception, its role in mediating itch remains to be investigated. Here, we reported that loss of FGF13 in mouse DRG neurons impaired the histamine-induced scratching behavior. Calcium imaging showed that the percentage of histamine-responsive DRG neurons was largely decreased in FGF13-deficient mice; and consistently, electrophysiological recording exhibited that histamine failed to evoke action potential firing in most DRG neurons from these mice. Given that the reduced histamine-evoked neuronal response was caused by knockdown of FGF13 but not by FGF13A deficiency, FGF13B was supposed to mediate this process. Furthermore, overexpression of histamine Type 1 receptor H1R, but not H2R, H3R, nor H4R, increased the percentage of histamine-responsive DRG neurons, and the scratching behavior in FGF13-deficient mice was hi...

For decades, a role for the Ca2+-binding protein calmodulin (CaM) in Ca2+-dependent presynaptic modulation of synaptic transmission has been recognized. Here, we investigated the influence of CaM on evoked and spontaneous neurotransmission at rod bipolar (RB) cell→AII amacrine cell synapses in the mouse retina. Our work was motivated by the observations that expression of CaM in RB axon terminals is extremely high and that [Ca2+] in RB terminals normally rises sufficiently to saturate endogenous buffers, making tonic CaM activation likely. Taking advantage of a model in which RBs can be stimulated by expressed channelrhodopsin-2 (ChR2) to avoid dialysis of the presynaptic terminal, we found that inhibition of CaM dramatically decreased evoked release by inhibition of presynaptic Ca channels while at the same time potentiating both Ca2+-dependent and Ca2+-independent spontaneous release. Remarkably, inhibition of myosin light chain kinase (MLCK), but not other CaM-dependent targets, mimicked the effects of ...

A multidimensional inflammatory response ensues after status epilepticus (SE), driven partly by cyclooxygenase-2 mediated activation of prostaglandin EP2 receptors. The inflammatory response is typified by astrocytosis, microgliosis, erosion of the blood-brain barrier (BBB), formation of inflammatory cytokines, and brain infiltration of blood-borne monocytes. Our previous studies have shown that inhibition of monocyte brain invasion or systemic administration of an EP2 receptor antagonist relieves multiple deleterious consequences of SE. Here we identify those effects of EP2 antagonism that are reproduced by conditional ablation of EP2 receptors in immune myeloid cells and show that systemic EP2 antagonism blocks monocyte brain entry in male mice. The induction of hippocampal IL-6 after pilocarpine SE was nearly abolished in EP2 conditional knockout mice. Serum albumin levels in the cortex, a measure of BBB breakdown, were significantly higher after SE in EP2-sufficient mice but not in EP2 conditional knoc...

Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulphate proteoglycans (CSPGs) which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates BDNF-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase sigma (PTPσ, PTPRS), receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTPσ deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTPσ deficient mice (PTPσ+/-). The antidepr...

Canonical language models describe eloquent function as the product of a series of cognitive processes, typically characterized by the independent activation profiles of focal brain regions. In contrast, more recent work has suggested that the interactions between these regions - the cortical networks of language - are critical for understanding speech production. We investigated the cortical basis of picture naming with human intracranial electrocorticography (ECoG) recordings and direct cortical stimulation (DCS), adjudicating between two competing hypotheses: Are task specific cognitive functions discretely computed within well-localized brain regions or rather by distributed networks? The time-resolution of ECoG allows direct comparison of intra regional activation measures (high-gamma power) with graph theoretic measures of inter regional dynamics. We developed an analysis framework, “ Net work dynamics using D irected I nformation” (NetDI), using information and graph theoretic tools to reveal spatio...

Prolyl 4-hydroxylases have vital roles in regulating collagen synthesis and hypoxia response. A transmembrane prolyl 4-hydroxylase (P4H-TM) is a recently identified member of the family. Biallelic loss of function P4H-TM mutations cause a severe autosomal recessive intellectual disability syndrome in humans, but functions of P4H-TM are essentially unknown at cellular level. Our microarray data on P4h-tm-/- mouse cortexes where P4H-TM is abundantly expressed, indicated expression changes in genes involved in calcium signaling and expression of several calcium sequestering ATPases was upregulated in P4h-tm-/- primary mouse astrocytes. Cytosolic and intraorganellar calcium imaging of P4h-tm-/- cells revealed that receptor and store-operated calcium entry and calcium re-uptake by mitochondria were compromized. HIF1, but not HIF2, was found to be a key mediator of the P4H-TM effect on calcium signaling. Furthermore, total internal reflection fluorescence imaging showed that calcium agonist-induced gliotransmiss...