Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in allevia...

So you understand the importance of science advocacy, but you’re struggling to fit it into your packed schedule. Understanding how advocacy plays a role in your professional success and scientific discovery more broadly could help you make time for this essential activity.

Recent neurophysiological studies provide inconsistent results of fronto-parietal network stimulation for altering working memory capacity. This study aimed to boost working memory capacity by manipulating the activity of the fronto-parietal network via dual-site High-Definition transcranial direct current stimulation. Forty-eight participants were randomly assigned to three stimulation groups, receiving either simultaneous anodal stimulation of the frontal and parietal areas (double stimulation), or stimulation of the frontal area only (single stimulation), or the placebo stimulation (sham) to frontal and parietal areas. After the stimulation, we used an Operation Span task to test memory accuracy, mathematical accuracy, time of calculation and memorizing and recall response time across the three groups. The results revealed an enhancement of memory accuracy and a reduction of time of calculation in the double stimulation group compared to others. In addition, recall response time was significantly decrea...

Perceptual decisions are often accompanied by a feeling of decision confidence. Where parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on (pre-)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electro-encephalography (EEG) was measured. ...

As rapid responders to their environments, microglia engage in functions that are mirrored by their cellular morphology. Microglia are classically thought to exhibit a ramified morphology under homeostatic conditions which switches to an ameboid form during inflammatory conditions. However, microglia display a wide spectrum of morphologies outside of this dichotomy, including rod-like, ramified, ameboid, and hypertrophic states, which have been observed across brain regions, neurodevelopmental timepoints, and various pathological contexts. We applied dimensionality reduction and clustering to consider contributions of multiple morphology measures together to define a spectrum of microglial morphological states in a mouse dataset we used to demonstrate the utility of our toolset. Using ImageJ, we first developed a semi-automated approach to characterize 27 morphology features from hundreds to thousands of individual microglial cells in a brain region-specific manner. Within this pool of features, we defined...

Increasing diversity in scientific programs requires practical changes, as well as vision and leadership. Learn strategies that you can replicate from Keith A. Trujillo, Lee E. Limbird, and Andrew G. Campbell as they discuss ways programs like Fisk-Vanderbilt Masters to PhD Bridge Program have successfully increased underrepresented minorities in science.

Generation of human induced pluripotent stem cell (hiPSC)-derived motor neurons (MNs) offers an unprecedented approach to modeling movement disorders such as dystonia and amyotrophic lateral sclerosis. However, achieving survival poses a significant challenge when culturing induced MNs, especially when aiming to reach late maturation stages. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we assembled two types of coculture systems: direct coculturing of neurons with astrocytes, and indirect coculture using culture inserts that physically separate neurons and astrocytes. Both systems significantly enhance neuron survival. Compared with these two systems, no significant differences in neurodevelopment, maturation, and survival within 3 weeks, allowing to prepare neurons at maturation stages. Using the indirect coculture system, we obtained highly pure MNs at the late mature stage from hiPSCs. Transcriptomic studies of hiPSC-derived MNs showed a typical neurodevelopmental switch in gene e...

Early-life stressors can affect reproductive development and change responses to adult stress. We tested if resource scarcity in the form of limited bedding and nesting (LBN) from postnatal days (PND) 4-11 delayed sexual maturation in male and female mice and/or altered the response to an acute, layered, psychosocial stress (ALPS) in adulthood. Contrary to the hypotheses, age and mass at puberty were unaffected by the present application of LBN. Further, under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, or proestrous females reared in standard or LBN environments were similar. ALPS disrupts the luteinizing hormone (LH) surge in most mice when applied on the morning of proestrus; this effect was not changed by resource scarcity. In this study, the paucity of effects in the offspring may relate to a milder response of CBA dams to the paradigm. While LBN dams exited the nest more often, and their offspring were smaller than standard-reared offspring on PND11, da...

Reading depends on a brain region known as the “visual word form area” (VWFA) in left ventral occipito-temporal cortex. This region’s function is debated because its stimulus selectivity is not absolute, it is modulated by a variety of task demands, and it is inconsistently localized. We used fMRI to characterize the combination of sensory and cognitive factors that activate word-responsive regions that we precisely localized in 16 adult humans (4 male). We then presented three types of character strings: English words, pseudowords, and unfamiliar characters with matched visual features. Participants performed three different tasks while viewing those stimuli: detecting real words, detecting color in the characters, and detecting color in the fixation mark. There were three primary findings about the VWFA’s response: (1) It preferred letter strings over unfamiliar characters even when the stimuli were ignored during the fixation task; (2) Compared to those baseline responses, engaging in the word reading t...

It has long been assumed that activity patterns persist in neuronal circuits after they are first experienced, as part of the process of information processing and storage by the brain. However, these “reverberations” of current activity have not been directly observed on a single neuron level in a mammalian system. Here we demonstrate that specific induced activity patterns are retained in mature cultured hippocampal neuronal networks. Neurons within the network are induced to fire at a single frequency or in a more complex pattern containing two distinct frequencies. After the stimulation was stopped, the subsequent neuronal activity of hundreds of neurons in the network was monitored. In the case of single-frequency stimulation, it was observed that many of the neurons continue to fire at the same frequency that they were stimulated to fire at. Using a Recurrent Neural Network (RNN) trained to detect specific, more complex patterns, we found that the multiple-frequency stimulation patterns were also ret...