We are able to temporally organize multiple movements in a purposeful manner in everyday life. Both the dorsal premotor (PMd) area and pre-supplementary motor area (pre-SMA) are known to be involved in the performance of motor sequences. However, it is unclear how each area differentially contributes to controlling multiple motor sequences. To address this issue, we recorded single-unit activity in both areas while monkeys (one male, one female) performed sixteen motor sequences. Each sequence comprised either a series of two identical movements (repetition) or two different movements (nonrepetition). The sequence was initially instructed with visual signals but had to be remembered thereafter. Here, we showed that the activity of single neurons in both areas transitioned from reactive- to predictive encoding while motor sequences were memorized. In the memory-guided trials, in particular, the activity of PMd cells preferentially represented the second movement (2M) in the sequence leading to a reward gene...

Astrocytes release functional mitochondria (Mt) that play regulatory and prosurvival functions on entering adjacent cells. We recently demonstrated that these released Mts could enter microglia to promote their reparative/prophagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, the relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt, which on entering the brain (and neurons), restored Mn-SOD levels and reduced neurological deficits in male mice subjected to ICH. Using an in vitro ICH-like injury model in cultured neurons, we established that astrocytic Mt on entering neurons prevented reactive oxygen species-induced...

In Drosophila melanogaster , the pacemaker located in the brain plays the main role in maintaining circadian rhythms; however, peripheral oscillators including glial cells, are also crucial components of the circadian network. In the present study, we investigated an impact of oscillators located in astrocyte-like glia, the chiasm giant glia of the optic lobe, epithelial and subperineurial glia on sleep of Drosophila males. We described that oscillators located in astrocyte-like glia and chiasm giant glia are necessary to maintain daily changes in clock neurons arborizations, while those located in epithelial glia regulate amplitude of these changes. Finally, we showed that communication between glia and neurons through tripartite synapses formed by epithelial glia and, in effect, neurotransmission regulation plays important role in wake-promoting during the day. SIGNIFICANCE STATEMENT Circadian clock or pacemaker regulates many aspects of animals' physiology and behavior. The pacemaker is located in the ...

Adam M. Tuttle, Matthew B. Pomaville, Katherine C. Delgado, Kevin M. Wright, and Alex V. Nechiporuk (see pages [6835–6847][1]) Most cancer drugs have significant toxic side effects. One such effect is chemotherapy-induced peripheral neuropathy, which results in numbness, burning, tingling

Dysregulation of excitatory and inhibitory signaling is commonly observed in major psychiatric disorders, including schizophrenia, depression, and bipolar disorder, and is often targeted by psychological and pharmacological treatment methods. The balance of excitation and inhibition is highly sensitive to severe psychological stress, one of the strongest risk factors for psychiatric disorders. The role of astrocytes in regulating excitatory and inhibitory signaling is now widely recognized; however, the specific involvement of astrocytes in the context of psychiatric disorders with a history of significant stress exposure remains unclear. In this review, we summarize how astrocytes regulate the balance of excitation and inhibition in the context of stress exposure and severe psychopathology, with a focus on the PFC, a brain area highly implicated in psychopathology. We first focus on preclinical models to demonstrate that the duration of stress (particularly acute vs chronic stress) is key to shaping astro...

During human seizures, organized waves of voltage activity rapidly sweep across the cortex. Two contradictory theories describe the source of these fast traveling waves: either a slowly advancing narrow region of multiunit activity (an ictal wavefront) or a fixed cortical location. Limited observations and different analyses prevent resolution of these incompatible theories. Here we address this disagreement by combining the methods and microelectrode array recordings ( N = 11 patients, 2 females, N = 31 seizures) from previous human studies to analyze the traveling wave source. We find, inconsistent with both existing theories, a transient relationship between the ictal wavefront and traveling waves, and multiple stable directions of traveling waves in many seizures. Using a computational model that combines elements of both existing theories, we show that interactions between an ictal wavefront and fixed source reproduce the traveling wave dynamics observed in vivo . We conclude that combining both exist...

Humans form impressions toward individuals of their own social groups (ingroup members) and of different social groups (outgroup members). Outgroup-focused theories predict that intergroup impressions are mainly shaped by experiences with outgroup individuals, while ingroup-focused theories predict that ingroup experiences play a dominant role. Here we test predictions from these two psychological theories by estimating how intergroup impressions are dynamically shaped when people learn from both ingroup and outgroup experiences. While undergoing fMRI, male participants had identical experiences with different ingroup or outgroup members and rated their social closeness and impressions toward the ingroup and the outgroup. Behavioral results showed an initial ingroup bias in impression ratings which was significantly reduced over the course of learning, with larger effects in individuals with stronger ingroup identification. Computational learning models revealed that these changes in intergroup impressions...

fMRI plays a key role in the study of attention. However, there remains a puzzling discrepancy between attention effects measured with fMRI and with electrophysiological methods. While electrophysiological studies find that attention increases sensory gain, amplifying stimulus-evoked neural responses by multiplicatively scaling the contrast-response function (CRF), fMRI appears to be insensitive to these multiplicative effects. Instead, fMRI studies typically find that attention produces an additive baseline shift in the BOLD signal. These findings suggest that attentional effects measured with fMRI reflect top-down inputs to visual cortex, rather than the modulation of sensory gain. If true, this drastically limits what fMRI can tell us about how attention improves sensory coding. Here, we examined whether fMRI is sensitive to multiplicative effects of attention using a feature-based attention paradigm designed to preclude any possible additive effects. We measured BOLD activity evoked by a probe stimulus...

Neuropsychological and neuroimaging studies have suggested that the primate amygdala plays an essential role in processing the emotional valence and intensity of visual stimuli, which is necessary for determining whether to approach or avoid a stimulus. However, the neuronal mechanisms underlying the evaluation of emotional value remain unknown. In the present study, we trained male macaque monkeys to perform an operant conditioning task in which fractal visual patterns were associated with three different amounts of air puff delivered to the cheek (negative) or liquid reward (positive). After confirming that the monkeys successfully differentiated the emotional valence and intensity of the visual stimuli, we analyzed neuronal responses to the stimuli in the amygdala. Most amygdala neurons conveyed information concerning the emotional valence and/or intensity of the visual stimuli, and the majority of those conveying information about emotional valence responded optimally to negative stimuli. Further, some...

As the central nervous system-resident macrophages and member of the myeloid lineage, microglia fulfill manifold functions important for brain development and homeostasis. In the context of neurodegenerative diseases, they have been implicated in de- and regenerative processes. The discovery of distinct activation patterns including increased phagocytosis indicated a damaging role of myeloid cells in multiple system atrophy (MSA), a devastating, rapidly progressing atypical parkinsonian disorder. Here, we analyzed the gene expression profile of microglia in a mouse model of MSA (MBP29-hα-syn) and identified a disease-associated expression profile and upregulation of the colony-stimulating factor 1 ( Csf1 ). Thus, we hypothesized that CSF1 receptor-mediated depletion of myeloid cells using PLX5622 modifies the disease progression and neuropathological phenotype in this mouse model. Intriguingly, sex-balanced analysis of myeloid cell depletion in MBP29-hα-syn mice revealed a two-faced outcome comprising an i...