Journal of Neuroscience

Perception has been proposed to result from the integration of feedforward sensory signals with internally generated feedback signals. Feedback signals are believed to play an important role in driving false percepts, i.e., seeing things that are not actually there. Feedforward and feedback influences on perception can be studied using layer-specific fMRI, which we used here to interrogate neural activity underlying high confidence false percepts while healthy human participants (N=25, male and female) performed a perceptual orientation discrimination task...

Chronic alcohol exposure leads to a neuroinflammatory response involving activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and pro-inflammatory cytokine production. Acute ethanol (EtOH) exposure activates GABAergic synapses in the central and basolateral amygdala (BLA) ex vivo , but whether this rapid modulation of synaptic inhibition is due to an acute inflammatory response and alters anxiety-like behavior in male and female animals is not known. Here, we tested the hypotheses that acute EtOH facilitates inhibitory synaptic transmission in the BLA by activating the NLRP3 inflammasome-dependent acute inflammatory response, that the alcohol-induced increase in inhibition is cell type- and sex-dependent, and that acute EtOH in the BLA reduces anxiety-like behavior...

Neuronal activity is modulated not only by inputs from other neurons but also by various factors, such as bioactive substances. Noradrenergic neurons in the locus coeruleus (LC-NA neurons) are involved in diverse physiological functions, including sleep/wakefulness and stress responses. Previous studies have identified various substances and receptors that modulate LC-NA neuronal activity through techniques including electrophysiology, calcium imaging, and single-cell RNA sequencing. However, many substances with unknown physiological significance have been overlooked...

Individuals with mutations in a single copy of the SHANK3 gene present with social-interaction deficits. Although social behavior in mice depends on olfaction, mice with mutations in a single copy of the Shank3 gene do not have olfactory deficits in simple odor identification tasks (Drapeau et al. 2018). Here we tested olfaction in mice with mutations in a single copy of the Shank3 gene (Peça et al. 2011) using a complex odor-task and imaging in awake mice. Average glomerular responses in the olfactory bulb of Shank3B+/- were correlated with WT mice...

Hearing is an active process and recent studies show that even the ear is affected by cognitive states or motor actions. One example are movements of the eardrum induced by saccadic eye movements - known as "eye movement-related eardrum oscillations" (EMREOs). While these are systematically shaped by the direction and size of saccades, the consequences of saccadic eye movements and their resulting EMREOs for hearing remain unclear. We here studied their implications for the detection of near-threshold clicks in human participants...

Larvae of the fruit fly Drosophila melanogaster are a powerful study case for understanding the neural circuits underlying behavior. Indeed, the numerical simplicity of the larval brain has permitted the reconstruction of its synaptic connectome, and genetic tools for manipulating single, identified neurons allow neural circuit function to be investigated with relative ease and precision. We focus on one of the most complex neurons in the brain of the larva (of either sex), the GABAergic anterior paired lateral neuron (APL)...

The medial nucleus of the trapezoid body (MNTB) in the auditory brainstem is the principal source of synaptic inhibition to several functionally distinct auditory nuclei. Prominent projections of individual MNTB neurons comprise the major binaural nuclei that are involved in the early processing stages of sound localization as well as the superior paraolivary nucleus (SPON), which contains monaural neurons that extract rapid changes in sound intensity to detect sound gaps and rhythmic oscillations that commonly occur in animal calls and human speech...

No abstract text is available yet for this article.

NR2D subunit-containing N-methyl-D-aspartate receptors (NMDARs) gradually disappear during brain maturation but can be recruited by pathophysiological stimuli in the adult brain. Here, we report that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication recruited NR2D subunit-containing NMDARs that generated an Mg2+ -resistant tonic NMDA current (INMDA ) in dopaminergic (DA) neurons in the midbrain of mature male mice. MPTP selectively generated an Mg2+ -resistant tonic INMDA in DA neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA)...

No abstract text is available yet for this article.

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in sub-populations of GBM cells...

The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been studied to understand sexual dimorphism, although the anatomy and physiology of the SDN is not fully understood. Here, we characterized SDN neurons that contribute to sexual dimorphism and investigated the mechanisms underlying the emergence of such neurons and their roles in social behaviors. A target-specific neuroanatomical study using transgenic mice expressing Cre recombinase under the control of Calb1 , a gene expressed abundantly in the SDN, revealed that SDN neurons are divided into two subpopulations: GABA neurons projecting to the ventral tegmental area (VTA), where they link to the dopamine system (CalbVTA neurons) and GABA neurons that extend axons in the MPOA or project to neighboring regions (CalbnonVTA neurons)...

Our muscles are the primary means through which we affect the external world, and the sense of agency (SoA) over the action through those muscles is fundamental to our self-awareness. However, SoA research to date has focused almost exclusively on agency over action outcomes rather than over the musculature itself, as it was believed that SoA over the musculature could not be manipulated directly. Drawing on methods from human-computer interaction and adaptive experimentation, we use human-in-the-loop Bayesian optimization to tune the timing of electrical muscle stimulation so as to robustly elicit a sense of agency over electrically-actuated muscle movements in male and female human subjects...

Because the sophistication of tool use is vastly enhanced in humans compared to other species, a rich understanding of its neural substrates requires neuroscientific experiments in humans. Although functional magnetic resonance imaging (fMRI) has enabled many studies of tool-related neural processing, surprisingly few studies have examined real tool use. Rather, due to the many constraints of fMRI, past research has typically used proxies such as pantomiming despite neuropsychological dissociations between pantomimed and real tool use...

Alzheimer's Disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared to non-demented individuals. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping impacts on the brain's functional connectome is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization towards AD characterization...

When humans reach to visual targets, extremely rapid (∼90 ms) target-directed responses can be observed in task-relevant proximal muscles. Such express visuomotor responses are inflexibly locked in time and space to the target and have been proposed to reflect rapid visuomotor transformations conveyed subcortically via the tecto-reticulo-spinal pathway. Previously, we showed that express visuomotor responses are sensitive to explicit cue-driven information about the target, suggesting that the express pathway can be modulated by cortical signals affording contextual pre-stimulus expectations...

Languages come in different forms but have shared meanings to convey. Some meanings are expressed by sentence structure and morphological inflections rather than content words, such as indicating time frame using tense. This fMRI study investigates whether there is cross-language common representation of grammatical meanings that can be identified from neural signatures in the bilingual human brain. Based on the representations in inter-sentence neural similarity space, identifying grammatical construction of a sentence in one language by models trained on the other language resulted in reliable accuracy...

In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared to novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli. SRP is dependent on NMDA receptors (NMDAR) and has been hypothesized to reflect potentiation of thalamocortical synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells...

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by memory loss and progressive cognitive impairments. In mouse models of AD pathology, studies have found neuronal and synaptic deficits in hippocampus, but less is known about changes in medial entorhinal cortex (MEC), which is the primary spatial input to the hippocampus and an early site of AD pathology. Here, we measured neuronal intrinsic excitability and synaptic activity in MEC layer II (MECII) stellate cells, MECII pyramidal cells, and MEC layer III (MECIII) excitatory neurons at 3 and 10 months of age in the 3xTg mouse model of AD pathology, using male and female mice...

Hippocampal activity linking past experiences and simulations of the future with current goals can play an important role in decision-making. The representation of information within the hippocampus may be especially critical in situations where one needs to overcome past rewarding experiences and exert self-control. Self-control success or failure may depend on how information is represented in the hippocampus and how effectively the representation process can be modified to achieve a specific goal. We test this hypothesis using representational similarity analyses of human (female/male) neuroimaging data during a dietary self-control task in which individuals must overcome taste temptations to choose healthy foods...