Anticipatory covert spatial attention improves performance on tests of visual detection and discrimination, and shifts are accompanied by decreases and increases of α band power at electroencephalography (EEG) electrodes corresponding to the attended and unattended location, respectively. Although the increase at the unattended location is often interpreted as an active mechanism (e.g., inhibiting processing at the unattended location), most experiments cannot rule out the alternative possibility that it is a secondary consequence of selection elsewhere. To adjudicate between these accounts, we designed a Posner-style visual cueing task in which male and female human participants made orientation judgments of targets appearing at one of four locations: up, down, right, or left. Critically, trials were blocked such that within a block the locations along one meridian alternated in status between attended and unattended, and targets never appeared at the other two, making them irrelevant. Analyses of the con...

Retinal ganglion cells (RGCs) die after optic nerve trauma or in degenerative disease. However, acute changes in protein expression that may regulate RGC response to injury are not fully understood, and detailed methods to quantify new protein synthesis have not been tested. Here, we develop and apply a new in vivo quantitative measure of newly synthesized proteins to examine changes occurring in the retina after optic nerve injury. Azidohomoalanine, a noncanonical amino acid, was injected intravitreally into the eyes of rodents of either sex with or without optic nerve injury. Isotope variants of biotin-alkyne were used for quantitative BONCAT (QBONCAT) mass spectrometry, allowing identification of protein synthesis and transport rate changes in more than 1000 proteins at 1 or 5 d after optic nerve injury. In vitro screening showed several newly synthesized proteins regulate axon outgrowth in primary neurons in vitro . This novel approach to targeted quantification of newly synthesized proteins after inju...

Calcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In embryonic mouse cortical neurons using glucose as only fuel, activation by NMDA elicits a strong workload (ATP demand)-dependent on Na+ and Ca2+ entry, and stimulates glucose uptake, glycolysis, pyruvate and lactate production, and oxidative phosphorylation (OXPHOS) in a Ca2+-dependent way. We find that Ca2+ upregulation of glycolysis, pyruvate levels, and respiration, but not glucose uptake, all depend on Aralar/AGC1/Slc25a12, the mitochondrial aspartate-glutamate carrier, component of the malate-aspartate shuttle (MAS). MAS activation increases glycolysis, pyruvate production, and respiration, a process inhibited in the presence of BAPTA-AM, suggesting that the Ca2+ binding motifs in Aralar may be involved in the activation. Mitochondrial calcium uniporter (MCU) silencing had no effect, indicating that none of these processes required MCU-dependent mitochondrial Ca2+ uptake. T...

Performing visual search tasks requires optimal attention deployment to promote targets and inhibit distractors. Rejection templates based on the distractor’s feature can be built to constrain the search process. We measured electroencephalography (EEG) of human participants of both sexes when they performed a visual search task in conditions where the distractor cues were constant within a block (fixed-cueing) or changed on a trial-by-trial basis (varied-cueing). In the fixed-cueing condition, sustained decoding of the cued colors could be achieved during the retention interval and the participants with higher decoding accuracy showed larger suppression benefits of the distractor cueing in the search period. In the varied-cueing condition, the cued color could only be transiently decoded after its onset and the higher decoding accuracy was observed from the participants who demonstrated lower suppression benefit. The differential neural representations of the to-be-ignored color in the two cueing conditio...

Vocal learning in songbirds is mediated by a highly localized system of interconnected forebrain regions, including recurrent loops that traverse the cortex, basal ganglia, and thalamus. This brain-behavior system provides a powerful model for elucidating mechanisms of vocal learning, with implications for learning speech in human infants, as well as for advancing our understanding of skill learning in general. A long history of experiments in this area has tested neural responses to playback of different song stimuli in anesthetized birds at different stages of vocal development. These studies have demonstrated selectivity for different song types that provide neural signatures of learning. In contrast to the ease of obtaining responses to song playback in anesthetized birds, song-evoked responses in awake birds are greatly reduced or absent, indicating that behavioral state is an important determinant of neural responsivity. Song-evoked responses can be elicited during sleep as well as anesthesia, and th...

Among the modulatory functions of thyrotropin-releasing hormone (TRH), an anorectic behavior in rodents is observed when centrally injected. Hypothalamic PVN neurons receive serotonergic inputs from dorsal raphe nucleus and express serotonin (5HT) receptors such as 5HT1A, 5HT2A/2C, 5HT6, which are involved in 5HT-induced feeding regulation. Rats subjected to dehydration-induced anorexia (DIA) model show increased PVN TRH mRNA expression, associated with their decreased food intake. We analyzed whether 5HT input is implicated in the enhanced PVN TRH transcription that anorectic rats exhibit, given that 5HT increases TRH expression and release when studied in vitro . By using mHypoA-2/30 hypothalamic cell cultures, we found that 5HT stimulated TRH mRNA, pCREB and pERK1/2 levels. By inhibiting basal PKA or PKC activities or those induced by 5HT, pCREB or pERK1/2 content did not increase suggesting involvement of both kinases in their phosphorylation. 5HT effect on TRH mRNA was not affected by PKA inhibition, ...

Visual word recognition has been proposed to have a functional and spatial organization corresponding to hierarchical language-like word forms in the left fusiform gyrus (FG) during visual word recognition in alphabetic languages. However, it is still unclear whether the similar functional gradients of word-like representation exist during Chinese character recognition. In this study, we adopted univariate activation analysis and representational similarity analysis (RSA) methods to investigate the functional organization in the FG for Chinese character recognition using task fMRI data. Native Chinese readers were visually presented with four types of character-like stimuli (i.e., real characters, pseudo-characters, false characters, and stroke combinations). After analysis, we observed a posterior-to-anterior functional gradient in the left FG corresponding to the degree of likeness of stimuli to character. Additionally, distinct sub-regions of the left FG harbor different orthographic codes. The middle p...

Steady-state visually evoked potentials (SSVEPs) are widely used to index top-down cognitive processing in human electroencephalogram (EEG) studies. Typically, two stimuli flickering at different temporal frequencies (TFs) are presented, each producing a distinct response in the EEG at its flicker frequency. However, how SSVEP responses in EEGs are modulated in the presence of a competing flickering stimulus just because of sensory interactions is not well understood. We have previously shown in local field potentials (LFPs) recorded from awake monkeys that when two overlapping full-screen gratings are counterphased at different TFs, there is an asymmetric SSVEP response suppression, with greater suppression from lower TFs, which further depends on the relative orientations of the gratings (stronger suppression and asymmetry for parallel compared with orthogonal gratings). Here, we first confirmed these effects in both male and female human EEG recordings. Then, we mapped the response suppression of one st...

Recent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context sensitivity is caused by faster updating of one's model of the world (i.e., higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing. An autism and matched control group of human adults (both n = 27, 8 female) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e., the standard and deviant sound in the first block) influences MMN a...

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are two types of cortical projection neurons (CPNs): those that project locally and interhemispherically and those that project to subcerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here, we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during mouse brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate (CP) during the formation of the superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditi...