Journal of Neuroscience最新文献

Selective attention is the collection of mechanisms through which the brain preferentially processes behaviorally important information. Many everyday tasks, such as shopping for groceries, require selective sampling of both external information (i.e., information from the environment) and internally stored information (i.e., information being maintained in working memory). While there is clear evidence that selective sampling of external information is influenced by internally stored information (and vice versa), the extent to which selective sampling of external and internal information compete for the same neural resources and attention-related processes remains a focus of debate. Previous research has linked theta-rhythmic (3-8 Hz) neural activity in higher-order (e.g., frontal cortices) and sensory regions to theta-rhythmic changes in behavioral performance during selective sampling. Here, we used electroencephalography and a dual-task design (i.e., a task that required both external and internal information), in male and female humans, to directly compare theta-dependent fluctuations in behavioral performance during external sampling with those during internal sampling. Our findings are consistent with a shared theta-rhythmic process for selectively sampling external information or internal information. This theta-rhythmic sampling is associated with both phase-dependent changes in sensory responses (i.e., as measured with the N1 component) and phase-dependent changes in interactions between external and internal information. The theta phase associated with weaker sensory responses and relatively worse behavioral performance (i.e., the "bad" phase) is also associated with a slowed perceptual decision-making process (as measured with the centroparietal positivity component), specifically during dual-task trials when to-be-detected external information matches to-be-remembered internal information.

Economic choice entails computing and comparing the subjective values of different goods. Orbitofrontal cortex (OFC) is thought to contribute to both operations. However, previous work focused almost exclusively on binary choices, raising the question of whether current notions hold for multinary choices. Here we recorded from male rhesus monkeys making trinary choices. Offers varied on three dimensions: juice flavor, quantity, and probability. In these experiments, quantity and probability varied continuously within a preset range. Animal choices were generally risk seeking and satisfied independence of irrelevant alternatives (IIA)-a fundamental assumption in standard economic theory. Different neurons encoded the values of individual offers, the choice outcome, and the chosen value-i.e., the same variables previously identified under binary choices. In addition, other cell groups encoded the chosen probability and the chosen hemifield. The activity of offer value cells reflected the risk attitude and fluctuated from session to session in ways that matched fluctuations observed behaviorally. In other words, the activity of these neurons reflected the subjective nature of value. Importantly, the representation of decision variables in OFC was invariant to changes in menu size-a property that effectively implies IIA.

Knowledge of how vocal communication signals are represented in the auditory system is crucial for understanding the perceptual basis of vocal communication. Using male and female zebra finches, we identified differentially expressed molecular markers that helped define distinct (caudal, rostral, dorsal, and ventral) domains within the caudomedial nidopallium (NCM), a high-order cortical auditory area known for its song-selective responses. Using expression analysis of the activity-inducible gene zenk, we found that the number of activated neurons is more stimulus dependent in NCM than in the auditory midbrain or the caudomedial mesopallium and that information on the density and spatial distribution of responsive neurons in NCM is sufficient to discriminate responses to conspecific song from other stimuli. We observed stronger activation of dorsal NCM, higher selectivity of caudal NCM toward conspecific song, and strong activation of the inhibitory network of rostral NCM by nonconspecific song stimuli. The spatial organization of responsive cells was particularly sensitive to both spectral and temporal components of song. We also obtained evidence of broadly distributed song-selective neuronal ensembles and that individual NCM neurons participate in the representation of different conspecific songs, implying independent activation and molecular induction responses. We conclude that some basic aspects of the cortical response to complex auditory stimuli are topographically organized, a finding that has been elusive in other systems. These findings advance our knowledge of the functional organization of a key song-processing cortical area, providing novel insights into the auditory representation of vocal communication signals.

Many studies have demonstrated that the basolateral complex of the amygdala (BLA) can facilitate offline consolidation processes in the hippocampus. However, an open question is how online neuronal oscillations in these regions dynamically couple at the moment of encoding to enable an episodic prioritization for important ecologically relevant stimuli. In the current study, local field potentials (LFPs) were recorded in the BLA and hippocampus (ventral CA1) of female rats as they spontaneously explored many novel and repeated plant-based odors and rat urine odors, which convey ecologically relevant information about conspecifics. Rats' estrous cycle was tracked and used to estimate sexual receptivity. Moments of exploring urine odors, particularly from male donors, were associated with different neural activity in the BLA and hippocampus versus plant-based odors, activity that also depended on the novelty of the odors as well as the rats' sexual receptivity. Specifically, prominent slow-gamma (20-50 Hz) oscillations during odor exploration showed a BLA-to-hippocampus directionality and were associated with odor novelty, odor category (male urine vs female urine vs plant-based odors), and better subsequent memory. Spiking-associated (150-200 Hz) activity in the LFPs was also influenced by odor novelty and odor category and was significantly higher in both the BLA and hippocampus on days for which the rats were sexually receptive. Thus, stimulus novelty and ecological relevance combined with the rats' emotional state to shape the neural correlates of prioritized encoding. The results are discussed in terms of endogenous mechanisms of memory enhancement for important to-be-remembered stimuli.

Parkinson's disease (PD) is a late-onset neurodegenerative disease characterized by preferential degeneration of midbrain dopaminergic neurons and α-synuclein-containing Lewy bodies that are found in both familial and sporadic forms. Genome-wide association studies (GWAS) have identified many loci associated with risk of sporadic PD, but their role in PD pathogenesis remains largely unknown. We screened a subset of GWAS genes in Caenorhabditis elegans (C. elegans) as potential modulators of α-synuclein-mediated degeneration of dopaminergic neurons. Loss of ari-2 (human ARIH2), an E3 ubiquitin ligase, was identified as the strongest suppressor of dopaminergic neurodegeneration in C. elegans. Unbiased proteomics analysis in human-induced pluripotent stem cell-derived dopaminergic neurons revealed novel substrates of ARIH2 including TPPP3, a regulator of microtubule dynamics. Importantly, TPPP3 was required for ARIH2's effects on α-synuclein-induced dopaminergic neurodegeneration. Our studies reveal an unexpected genetic interaction between two PD-linked genes, α-synuclein and ARIH2, and suggest that inhibition of ARIH2's enzymatic activity may serve as a potential therapeutic approach in PD.

In visually complex and dynamically changing environments, humans must often filter out salient but task-irrelevant stimuli. Prior work shows that with repeated exposure to color singleton distractors, individuals can learn to divert attention away from these salient items. However, the neural mechanisms supporting such attentional suppression remain unclear. The present study examined the temporal trajectories of singleton distractor representations during visual search to address this gap. Using multivariate pattern analyses of EEG data in human subjects (N = 40, 30 females, 10 males), we identified two clusters of decodable singleton distractor representations: an early cluster from 100 to 200 ms and a later cluster from 200 to 400 ms. Temporal generalization analyses showed that the later representations were inverted versions of the early ones. Importantly, stronger late but not early representations predicted faster search responses, suggesting that the later signals support distractor suppression. This representational inversion facilitates suppressing singleton distractors in the spatial priority map. Comparing decoding evidence across locations revealed that singleton distractor locations were suppressed relative to nonsingleton distractors. Moreover, comparing the neural coding of locations revealed that the spatial organization in the singleton distractor neural space was inverted relative to that in the target neural space. Together, these findings reveal a rapid representational inversion underlying salient distractor suppression at the onset of visual search. This inversion of singleton distractor signals was likely driven by top-down control mechanisms that transform bottom-up saliency signals, producing an inverted arrangement of target and distractor information within a shared neural space.

Mathematical learning disabilities (MLD) affect up to 14% of school-age children, yet the underlying neurocognitive mechanisms remain elusive. We developed drift diffusion model with dynamic performance monitoring (DDM-DPM), an innovative cognitive model that captures both external and internal sources of structural variability in task performance. Combining DDM-DPM with functional brain imaging, we examined symbolic and nonsymbolic quantity discrimination in female and male children with MLD and typically developing children matched on age, gender, and IQ. Children with MLD showed format-dependent alterations in response caution and posterror adjustment, despite similar observed performance measures between groups. The latent cognitive processes during symbolic quantity discrimination predicted broader mathematical abilities better than those during nonsymbolic quantity discrimination. Neuroimaging results revealed that reduced activity in middle frontal gyrus mediated deficits in response caution in symbolic format, while reduced activity in the anterior cingulate cortex mediated deficits in posterror adjustment in symbolic format in children with MLD. These findings provide novel support for a multidimensional deficit view of MLD that extends beyond basic number processing to include metacognitive processes. Our findings also provide novel support for and extend the access deficit model, which posits that individuals with MLD may have relatively intact quantity representations but struggle with numerical representations in symbolic formats. Our study highlights the value of integrating latent cognitive modeling with neuroimaging to reveal subtle mechanisms underlying learning disabilities and identify potential targets for intervention.

Establishing learned associations between rewarding stimuli and the context under which those rewards are encountered is critical for survival. Hippocampal input to the nucleus accumbens (NAc) provides important environmental context to reward processing to support goal-directed behaviors. This connection consists of two independent pathways originating from the dorsal (dHipp) or ventral hippocampus (vHipp), which have previously been considered functionally and anatomically distinct. Here, we show overlap in dHipp and vHipp terminal fields in the NAc, leading us to reconsider this view and raise new questions regarding the potential interactions between dHipp and vHipp pathways in the NAc. Using optogenetics, electrophysiology, and transsynaptic labeling in male and female mice, we investigated anatomical and functional convergence of dHipp and vHipp inputs in the NAc. Transsynaptic labeling revealed a subpopulation of dually innervated cells in the NAc medial shell, confirmed by independent optogenetic manipulation of dHipp and vHipp inputs during whole-cell electrophysiological recordings. Further analysis revealed closely apposed dHipp and vHipp inputs along dendritic branches, and simultaneous stimulation of both inputs elicited heterosynaptic potentiation. Comparison of observed and theoretical success rates suggests heterosynaptic interactions may occur presynaptically. Altogether, these results demonstrate that inputs originating from dHipp and vHipp converge onto a subset of NAc neurons with synapses positioned to enable rapid heterosynaptic interactions, indicating integration of these inputs at the single-neuron level. Exploring the physiological and behavioral implications of this convergence will offer new insights into how individual neurons incorporate information from distinct inputs and how this integration may shape learning.

Higher order (HO) thalamic nuclei are characterized by receiving driver input from layer 5 (L5) of cortex and serve as a transthalamic route of corticocortical communication. These HO nuclei are also innervated by subcortical sources. In the posterior medial nucleus (POm), a somatosensory HO thalamic nucleus, excitatory glutamatergic inputs arise from L5 of sensorimotor cortices and the spinal trigeminal nucleus (SpV), while inhibitory GABAergic sources are the anterior pretectal nucleus (APn) and zona incerta (ZI). Here, we tested a key postulate of transthalamic pathway function: that their disynaptic nature allows information traversing them from L5 to be modulated or gated by other inputs. We used optogenetics in acute slices from mice (both sexes) to test individual POm relays for convergent innervation. We found that modulatory inputs from SpV intersect with drivers from L5 of somatosensory cortex. Further, GABAergic inputs from the APn converge with both L5 and SpV inputs. In contrast, we found minimal convergence between ZI and L5 or SpV-a surprise considering previous evidence that ZI blocks whisker-dependent activation of POm relays. Therefore, we sought alternative explanations for this discrepancy. First, we detected robust convergence in POm between the ZI (and APn) and superior colliculus, which is whisker responsive. Second, we discovered that ZI innervates the thalamic reticular nucleus with glutamatergic synapses, comprising an alternative feedforward inhibitory circuit to POm. These results substantiate several mechanisms by which transthalamic information is modulated or gated while enhancing the resolution of our understanding of POm function.