Neural oscillations are thought to reflect low-level operations that can be used for higher-level cognitive functions. Here, we investigated the role of brain rhythms in the 1–30 Hz range by recording MEG in human participants performing a visual delayed match-to-sample paradigm in which orientation or spatial frequency of sample and probe gratings had to be matched. A cue occurring before or after sample presentation indicated the to-be-matched feature. We demonstrate that alpha/beta power decrease tracks the presentation of the informative cue and indexes faster responses. Moreover, these faster responses coincided with an augmented phase alignment of slow oscillations, as well as phase–amplitude coupling between slow and fast oscillations. Importantly, stimulus decodability was boosted by both low alpha power and high beta power. In summary, we provide support for a comprehensive framework in which different rhythms play specific roles: slow rhythms control input sampling, while alpha (and beta) gates t...

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA; 2 h/d) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats. Here, we assess the effects of long-access (LgA; 6 h/d) cocaine self-administration and abstinence on NAc astrocytes separately in male and female rats, employing a commonly used behavioral approach to investigate the incubation of cocaine craving. NAc astrocytes from male rats exhibit extensive (∼40%) reductions in surface area, volume, and postsynaptic colocalization 45 d but not 24 h after the last self-administration session. In contrast, no effect of self-administration and a...

Dopamine (DA) is a critical regulator of striatal network activity and is essential for motor activation and reward-associated behaviors. Previous work has shown that DA is influenced by the reward value of food, as well as by hormonal factors that reguate food intake and energy expenditure. Changes in striatal DA signaling also have been linked to aberrant eating patterns. Here we test the effect of leptin, an adipocyte-derived hormone involved in feeding and energy homeostasis regulation, on striatal DA release and uptake. Immunohistochemical evaluation identified leptin receptor (LepR) expression throughout mouse striatum, including on striatal cholinergic interneurons (ChIs) and their extensive processes. Using fast-scan cyclic voltammetry (FSCV), we found that leptin causes a concentration-dependent increase in evoked extra-cellular DA concentration ([DA]o) in dorsal striatum (dStr) and nucleus accumbens (NAc) core and shell in male mouse striatal slices, and also an increase in the rate of DA uptake....

Central pattern generators produce many rhythms necessary for survival (e.g., chewing, breathing, locomotion), and doing so often requires coordination of neurons through electrical synapses. Because even neurons of the same type within a network are often differentially tuned, uniformly applied neuromodulators or toxins can result in uncoordinated activity. In the crab ( Cancer borealis ) cardiac ganglion, potassium channel blockers and serotonin cause increased depolarization of the five electrically coupled motor neurons as well as loss of the normally completely synchronous activity. Given time, compensation occurs that restores excitability and synchrony. One of the underlying mechanisms of this compensation is an increase in coupling among neurons. However, the salient physiological signal that initiates increased coupling has not been determined. Using male C. borealis , we show that it is the loss of synchronous voltage signals between coupled neurons that is at least partly responsible for plastic...

Maria Mancini, Jyoti C. Patel, Alison H. Affinati, Paul Witkovsky, and Margaret E. Rice (see pages [6668–6679][1]) The hormone leptin is released by adipocytes in proportion to the amount of stored fat, and it acts in the brain to regulate food intake and energy expenditure. The rewarding value

The complex pathophysiology of post-traumatic brain damage might need a polypharmacological strategy with a combination of drugs that target multiple, synergistic mechanisms. We currently tested a combination of apocynin (curtails formation of reactive oxygen species), tert-butylhydroquinone (promotes disposal of reactive oxygen species), and salubrinal (prevents endoplasmic reticulum stress) following a moderate traumatic brain injury (TBI) induced by controlled cortical impact in adult mice. Adult mice of both sexes treated with the above tri-combo showed alleviated motor and cognitive deficits, attenuated secondary lesion volume, and decreased oxidative DNA damage. Concomitantly, tri-combo treatment regulated post-TBI inflammatory response by decreasing the infiltration of T cells and neutrophils and activation of microglia in both sexes. Interestingly, sexual dimorphism was seen in the case of TBI-induced microgliosis and infiltration of macrophages in the tri-combo–treated mice. Moreover, the tri-comb...

The activation of self-destructive cellular programs helps sculpt the nervous system during development, but the molecular mechanisms used are not fully understood. Prior studies have investigated the role of the APP in the developmental degeneration of sensory neurons with contradictory results. In this work, we sought to elucidate the impact of APP deletion in the development of the sensory nervous system in vivo and in vitro. Our in vivo data show an increase in the number of sciatic nerve axons in adult male and female APP-null mice, consistent with the hypothesis that APP plays a pro-degenerative role in the development of peripheral axons. In vitro , we show that genetic deletion of APP delays axonal degeneration triggered by nerve growth factor deprivation, indicating that APP does play a pro-degenerative role. Interestingly, APP depletion does not affect caspase-3 levels but significantly attenuates the rise of axoplasmic Ca2+ that occurs during degeneration. We examined intracellular Ca2+ mechanis...

According to a prominent view in neuroscience, visual stimuli are coded by discrete cortical networks that respond preferentially to specific categories, such as faces or objects. However, it remains unclear how these category-selective networks respond when viewing conditions are cluttered, i.e., when there is more than one stimulus in the visual field. Here, we asked three questions: (1) Does clutter reduce the response and selectivity for faces as a function of retinal location? (2) Is the preferential response to faces uniform across the visual field? And (3) Does the ventral visual pathway encode information about the location of cluttered faces? We used fMRI to measure the response of the face-selective network in awake, fixating macaques (two female, five male). Across a series of four experiments, we manipulated the presence and absence of clutter, as well as the location of the faces relative to the fovea. We found that clutter reduces the response to peripheral faces. When presented in isolation,...

Individual differences among human brains exist at many scales, spanning gene expression, white matter tissue properties, and the size and shape of cortical areas. One notable example is an approximately 3-fold range in the size of human primary visual cortex (V1), a much larger range than is found in overall brain size. A previous study ([Andrews et al., 1997][1]) reported a correlation between optic tract (OT) cross-section area and V1 size in postmortem human brains, suggesting that there may be a common developmental mechanism for multiple components of the visual pathways. We evaluated the relationship between properties of the OT and V1 in a much larger sample of living human brains by analyzing the Human Connectome Project (HCP) 7 Tesla Retinotopy Dataset (including 107 females and 71 males). This dataset includes retinotopic maps measured with functional MRI (fMRI) and fiber tract data measured with diffusion MRI (dMRI). We found a negative correlation between OT fractional anisotropy (FA) and V1 s...

The sunk cost effect refers to the fact that human decisions are consistently influenced by previous irrecoverable and irrelevant costs. Recent neuroimaging experiments suggest that the dorsolateral prefrontal cortex (dlPFC) plays a pivotal role in the sunk cost effect yet the causal and neurocomputational role of the dlPFC remains elusive. In this study, two cohorts of healthy human male and female adults were recruited to complete a novel two-step decision-making task during the anodal-sham or cathodal-sham high-definition transcranial direct current stimulation (HD-tDCS) over the dlPFC, respectively. Consistent with previous studies, we showed that the sunk cost deterred participants from making further investment and therefore engendered a de-escalation effect. Such behavior can be captured by a weighted mental accounting model with a recalibrated reference point in which the direction and magnitude of the sunk cost effects hinge on the decision weights apportioned to the option values. Interestingly, ...