Doublecortin-immunoreactive neurons in the piriform cortex are sensitive to the long lasting effects of early life stress.

The olfactory system is a niche of continuous structural plasticity, holding postnatal proliferative neurogenesis in the olfactory bulbs and a population of immature neurons in the piriform cortex. These neurons in the piriform cortex are generated during embryonic development, retain the expression of immaturity markers such as doublecortin, and slowly mature and integrate into the olfactory circuit as the animal ages. To study how early life experiences affect this population of cortical immature neurons, we submitted mice of the C57/Bl6J strain to a protocol of maternal separation for 3 h per day from postnatal day 3 to postnatal day 21. Control mice were continuously with their mothers. After weaning, mice were undisturbed until 6 weeks of age, when they were weighted and tested in the elevated plus-maze, a standard test for anxiety-like behavior, to check for phenotypical effects. Mice were then perfused, and their brains processed for the immunofluorescent detection of doublecortin and the endogenous proliferation marker Ki67. We found that maternal separation induced a significant increase in the body weight of males, but not females. Further, maternally separated mice displayed increased exploratory-like behavior (i.e., head dipping, velocity and total distance traveled in the elevated plus maze), but no significant differences in anxiety-like behavior or corticosterone levels after behavioral testing. Finally, we observed a significant increase in the number of complex doublecortin neurons in the piriform cortex, but not in the olfactory bulbs, of mice submitted to maternal separation. Interestingly, most doublecortin neurons in the piriform cortex, but not the olfactory bulb, express the epigenetic reader MeCP2. In summary, mild early life stress results, during adolescence, in a male-specific increase in body weight, alteration of the exploratory behaviors, and an increase in doublecortin neurons in the piriform cortex, suggesting an alteration in their maturation process.

Study of a precise treatment protocol for patients with consciousness disorders based on the brain network analysis of functional magnetic resonance imaging.

Objective: How to conduct objective and accurate individualized assessments of patients with disorders of consciousness (DOC) and carry out precision rehabilitation treatment technology is a major rehabilitation problem that needs to be solved urgently. Methods: In this study, a multi-layer brain network was constructed based on functional magnetic resonance imaging (fMRI) to analyze the structural and functional brain networks of patients with DOC at different levels and to find regulatory targets (imaging markers) with recovery potential for DOC. Then repeated transcranial magnetic stimulation (rTMS) was performed in DOC patients to clinically validate. Results: The brain network connectivity of DOC patients with different consciousness states is different, and the most obvious brain regions appeared in the olfactory cortex and precuneus. rTMS stimulation could effectively improve the consciousness level of DOC patients and stimulate the occipital lobe (specific regions found in this study) and the dorsolateral prefrontal cortex (DLPFC), and both parts had a good consciousness recovery effect. Conclusion: In clinical work, personalized stimulation regimen treatment combined with the brain network characteristics of DOC patients can improve the treatment effect.

Tactile stimulation designs adapted to clinical settings result in reliable fMRI-based somatosensory digit maps.

Movement constraints in stroke survivors are often accompanied by additional impairments in related somatosensory perception. A complex interplay between the primary somatosensory and motor cortices is essential for adequate and precise movements. This necessitates investigating the role of the primary somatosensory cortex in movement deficits of stroke survivors. The first step towards this goal could be a fast and reliable functional Magnetic Resonance Imaging (fMRI)-based mapping of the somatosensory cortex applicable for clinical settings. Here, we compare two 3 T fMRI-based somatosensory digit mapping techniques adapted for clinical usage in seven neurotypical volunteers and two sessions, to assess their validity and retest-reliability. Both, the traveling wave and the blocked design approach resulted in complete digit maps in both sessions of all participants, showing the expected layout. Similarly, no evidence for differences in the volume of activation, nor the activation overlap between neighboring activations could be detected, indicating the general feasibility of the clinical adaptation and their validity. Retest-reliability, indicated by the Dice coefficient, exhibited reasonable values for the spatial correspondence of single digit activations across sessions, but low values for the spatial correspondence of the area of overlap between neighboring digits across sessions. Parameters describing the location of the single digit activations exhibited very high correlations across sessions, while activation volume and overlap only exhibited medium to low correlations. The feasibility and high retest-reliabilities for the parameters describing the location of the single digit activations are promising concerning the implementation into a clinical context to supplement diagnosis and treatment stratification in upper limb stroke patients.

Spatiotemporal regulation of MELK during mitosis.

Maternal Embryonic Leucine Zipper Kinase (MELK) has been studied intensively in recent years due to its overexpression in multiple cancers. However, the cell biology of MELK remains less characterized despite its well-documented association with mitosis. Here we report a distinctive pattern of human MELK that translocates from the cytoplasm to cell cortex within 3 min of anaphase onset. The cortex association lasts about 30 min till telophase. The spatiotemporal specific localization of MELK depends on the interaction between its Threonine-Proline (TP) rich domain and kinase associated 1 (KA1) domain, which is regulated by CDK1 kinase and PP4 protein phosphatase. KA1 domains are known to regulate kinase activities through various intramolecular interactions. Our results revealed a new role for KA1 domain to control subcellular localization of a protein kinase.

Astrocytic P2X7 receptor in retrosplenial cortex drives electroacupuncture analgesia.

P2X7 receptor (P2X7R) has been found to contribute to the peripheral mechanism of acupuncture analgesia (AA). However, whether it plays an important role in central mechanism remains unknown. In this study, we aimed to reveal the role of astrocytic P2X7R in retrosplenial cortex (RSC) in AA and provide new evidence for underlying the central mechanism of AA. We applied the chemogenetic receptors hM3Dq to stimulate or hM4Di to inhibit astrocytes ligand clozapine-N-oxide (CNO) following injection of adeno-associated virus (AAV) into the bilateral RSC, or pharmacologically intervened in the activity of the purinergic receptor P2X7R. Current data indicated that chemogenetic inhibition of astrocytes or injection of P2X7R agonist Bz-ATP in the bilateral RSC significantly reverses the analgesic effect of electroacupuncture (EA) in formalin tests while the bilateral injection of the P2X7R antagonist A438079 alleviated formalin-induced nociceptive behavior. Additionally, chemogenetic suppression of astrocytic P2X7R by injection of AAV in the bilateral RSC decreased hind paw flinches induced by formalin in the mice. These findings indicate the participation of both astrocytes and P2X7R in the RSC in EA analgesic. Moreover, P2X7R on astrocytes in the RSC appears to play a critical role in the ability of EA to attenuate formalin-induced pain responses in mice.

Improving Prefrontal Oxygenation and Cardiac Autonomic Activity Following Meditation: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

OBJECTIVE: The empirical evidence explicitly demonstrates that meditation practice enhances both brain functions and mental well-being. A meditative relaxation approach called the mind sound resonance technique (MSRT) has shown promising effects on children, adolescents, and people with psychological illnesses. This study aimed to investigate the effects of MSRT practice on brain hemodynamics, heart rate variability (HRV), mindfulness, and anxiety levels in college students. METHODS: Fifty volunteers in all genders (females, n = 30; males, n = 20) aged between 19 and 30 years were chosen from an educational institute and allocated into two groups, i.e., MSRT (n = 25) and supine rest (SR; n = 25). Enrolled participants were measured cerebral hemodynamics and HRV before, during, and after the MSRT or SR practice. The self-reported assessments including state anxiety and mindfulness were assessed before and after the intervention. RESULTS: The results demonstrated that practicing MSRT significantly improved oxygenation (p < 0.05) in the right prefrontal cortex (PFC) and increased low-frequency (LF) (p < 0.05) and decreased high-frequency (HF) (p < 0.05) component of HRV when compared to the baseline. The between-group analysis showed a significant difference between MSRT and SR in the standard deviation of the normal-to-normal (SDNN) (p < 0.05) component of HRV. CONCLUSION: These crumbs of evidence imply that MSRT sessions may foster the development of anxiety-related coping skills by elevating mindfulness, promoting PFC oxygenation, and modulating HRV in MSRT practitioners.

Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure-Like Activities.

The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found. Kainate receptors (KAR)-mediated synaptic transmission is increased in this corticostriatal connection both in vitro and in vivo seizure-like activities. GluK1 containing KARs and downstream calcium-stimulated adenylyl cyclase subtype 1 (AC1) are involved in the upregulation of KARs following seizure-like activities. Inhibiting the activities of ACC or its corticostriatal connection significantly attenuated pentylenetetrazole (PTZ)-induced seizure. Additionally, injection of GluK1 receptor antagonist UBP310 or the AC1 inhibitor NB001 both show antiepileptic effects. The studies provide direct evidence that KARs are involved in seizure activity in the corticostriatal connection and the KAR-AC1 signaling pathway is a potential novel antiepileptic strategy.

Neural substrate for the engagement of the ventral visual stream in motor control in the macaque monkey.

The present study aimed to describe the cortical connectivity of a sector located in the ventral bank of the superior temporal sulcus in the macaque (intermediate area TEa and TEm [TEa/m]), which appears to represent the major source of output of the ventral visual stream outside the temporal lobe. The retrograde tracer wheat germ agglutinin was injected in the intermediate TEa/m in four macaque monkeys. The results showed that 58-78% of labeled cells were located within ventral visual stream areas other than the TE complex. Outside the ventral visual stream, there were connections with the memory-related medial temporal area 36 and the parahippocampal cortex, orbitofrontal areas involved in encoding subjective values of stimuli for action selection, and eye- or hand-movement related parietal (LIP, AIP, and SII), prefrontal (12r, 45A, and 45B) areas, and a hand-related dysgranular insula field. Altogether these data provide a solid substrate for the engagement of the ventral visual stream in large scale cortical networks for skeletomotor or oculomotor control. Accordingly, the role of the ventral visual stream could go beyond pure perceptual processes and could be also finalized to the neural mechanisms underlying the control of voluntary motor behavior.

Executive functions in psychopathy: a meta-analysis of inhibition, planning, shifting, and working memory performance.

Much research has focused on executive function (EF) impairments in psychopathy, a severe personality disorder characterized by a lack of empathy, antisocial behavior, and a disregard for social norms and moral values. However, it is still unclear to what extent EF deficits are present across psychopathy factors and, more importantly, which EF domains are impaired. The current meta-analysis answers these questions by synthesizing the results of 50 studies involving 5,694 participants from 12 different countries. Using multilevel random-effects models, we pooled effect sizes (Cohen's d) for five different EF domains: overall EF, inhibition, planning, shifting, and working memory. Moreover, differences between psychopathy factors were evaluated. Our analyses revealed small deficits in overall EF, inhibition, and planning performance. However, a closer inspection of psychopathy factors indicated that EF deficits were specific to lifestyle/antisocial traits, such as disinhibition. Conversely, interpersonal/affective traits, such as boldness, showed no deficits and in some cases even improved EF performance. These findings suggest that EF deficits are not a key feature of psychopathy per se, but rather are related to antisociality and disinhibitory traits. Potential brain correlates of these findings as well as implications for future research and treatment are discussed.

Sources of Rapid and Delayed New Lower Jaw Input in the Forepaw Barrel Subfield (FBS) in Rat Primary Somatosensory Cortex (SI) Following Forelimb Deafferentation.

Previously, we reported an immediate emergence of new lower jaw input to the anterior forepaw barrel subfield (FBS) in primary somatosensory cortex (SI) following forelimb deafferentation. However, a delay of 7 weeks or more post-amputation results in the presence of this new input to both anterior and posterior FBS. The immediate change suggests pre-existing latent lower jaw input in the FBS, whereas the delayed alteration implies the involvement of alternative sources. One possible source for immediate lower jaw responses is the neighboring lower jaw barrel subfield (LJBSF). We used anatomical tracers to investigate the possible projection of LJBSF to the FBS in normal and forelimb-amputated rats. Our findings are as follows: (1) anterograde tracer injection into LJBSF in normal and amputated rats labeled fibers and terminals exclusively in the anterior FBS; (2) retrograde tracer injection in the anterior FBS in normal and forelimb-amputated rats, heavily labeled cell bodies predominantly in the posterior LJBSF, with fewer in the anterior LJBSF; (3) retrograde tracer injection in the posterior FBS in normal and forelimb-amputated rats, sparsely labeled cell bodies in the posterior LJBSF; (4) retrograde tracer injection in anterior and posterior FBS in normal and forelimb-amputated rats, labeled cells exclusively in ventral posterior lateral (VPL) nucleus and posterior thalamus (PO); (5) retrograde tracer injection in LJBSF-labeled cell bodies exclusively in ventral posterior medial thalamic nucleus and PO. These findings suggest that LJBSF facilitates rapid lower jaw reorganization in the anterior FBS, whereas VPL and/or other subcortical sites provide a likely substrate for delayed reorganization observed in the posterior FBS.

Neural activation changes following attention bias modification treatment or a selective serotonin reuptake inhibitor for social anxiety disorder.

BACKGROUND: Delineation of changes in neural function associated with novel and established treatments for social anxiety disorder (SAD) can advance treatment development. We examined such changes following selective serotonin reuptake inhibitor (SSRI) and attention bias modification (ABM) variant - gaze-contingent music reward therapy (GC-MRT), a first-line and an emerging treatments for SAD. METHODS: Eighty-one patients with SAD were allocated to 12-week treatments of either SSRI or GC-MRT, or waitlist (ns = 22, 29, and 30, respectively). Baseline and post-treatment functional magnetic resonance imaging (fMRI) data were collected during a social-threat processing task, in which attention was directed toward and away from threat/neutral faces. RESULTS: Patients who received GC-MRT or SSRI showed greater clinical improvement relative to patients in waitlist. Compared to waitlist patients, treated patients showed greater activation increase in the right inferior frontal gyrus and anterior cingulate cortex when instructed to attend toward social threats and away from neutral stimuli. An additional anterior cingulate cortex cluster differentiated between the two active groups. Activation in this region increased in ABM and decreased in SSRI. In the ABM group, symptom change was positively correlated with neural activation change in the dorsolateral prefrontal cortex. CONCLUSIONS: Brain function measures show both shared and treatment-specific changes following ABM and SSRI treatments for SAD, highlighting the multiple pathways through which the two treatments might work. Treatment-specific neural responses suggest that patients with SAD who do not fully benefit from SSRI or ABM may potentially benefit from the alternative treatment, or from a combination of the two. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03346239. https://clinicaltrials.gov/ct2/show/NCT03346239.

Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Introduction: Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats. Materials and Methods: Male and female neonatal Sprague Dawley rats were treated with CBD (50 mg/kg) intraperitoneally on postnatal day (PND) 1, 3, and 5 and evaluated for behavioral and neuronal morphological changes during early adulthood. Rats were subjected to a series of behavioral tasks to evaluate long-term effects of neonatal CBD exposure, including the Barnes maze, open field, and elevated plus maze paradigms to assess spatial memory and anxiety-like behavior. Following behavioral evaluation, animals were sacrificed, and neuronal morphology of the cortex and hippocampus was assessed using Golgi-Cox (GC) staining. Results: Rats treated with CBD displayed a sexually dimorphic response in spatial memory, with CBD-treated females developing a deficit but not males. CBD did not elicit alterations in anxiety-like behavior in either sex. Neonatal CBD caused an overall decrease in dendritic length and spine density (apical and basal) in cortical and hippocampal neurons in both sexes. Sholl analysis also revealed a decrease in dendritic intersections in the cortex and hippocampus, indicating reduced dendritic arborization. Conclusions: This study provides evidence that neonatal CBD exposure perturbs normal brain development and leads to lasting alterations in spatial memory and neuronal dendrite morphology in early adulthood, with sex-dependent sensitivity.

Association of Compensatory Mechanisms in Prefrontal Cortex and Impaired Anatomical Correlates in Semantic Verbal Fluency: A Functional Near-Infrared Spectroscopy Study.

OBJECTIVE: Semantic verbal fluency (SVF) engages cognitive functions such as executive function, mental flexibility, and semantic memory. Left frontal and temporal lobes, particularly the left inferior frontal gyrus (IFG), are crucial for SVF. This study investigates SVF and associated neural processing in older adults with mild SVF impairment and the relationship between structural abnormalities in the left IFG and functional activation during SVF in those individuals. METHODS: Fifty-four elderly individuals with modest level of mild cognitive impairment whose global cognition were preserved to normal but exhibited mild SVF impairment were participated. Prefrontal oxyhemoglobin (HbO2) activation and frontal cortical thickness were collected from the participants using functional near-infrared spectroscopy (fNIRS) and brain MRI, respectively. We calculated the ß coefficient of HbO2 activation induced by tasks, and performed correlation analysis between SVF induced HbO2 activation and cortical thickness in frontal areas. RESULTS: We observed increased prefrontal activation during SVF task compared to the resting and control task. The activation distinct to SVF was identified in the midline superior and left superior prefrontal regions (p<0.05). Correlation analysis revealed an inverse relationship between SVF-specific activation and cortical thickness in the left IFG, particularly in pars triangularis (r(54)=-0.304, p=0.025). CONCLUSION: The study contributes to understanding the relationship between reduced cortical thickness in left IFG and increased functional activity in cognitively normal individuals with mild SVF impairment, providing implications on potential compensatory mechanisms for cognitive preservation.

Exploring symptomatology and innovative treatment modalities for prefrontal cortex lesions: a systematic review.

BACKGROUND: Pre-frontal cortex operates a combination of emotional, cognitive and behavioural functions. Understanding the symptoms of pre-frontal cortex lesions serves as paramount for accurate diagnosis and management. AIMS: This review aims to determine an association between the causes of prefrontal cortex lesions and the resulting symptoms, as well as the ideal form of treatment. STUDY DESIGN: A systematic review through utilisation of 3 databases was done using the keywords "Prefrontal cortex lesions," "dysfunction," "symptoms," &" treatment". METHODOLOGY: RCTs, observational studies, and systematic reviews were searched using Cochrane/EMBASE, PubMed/Medline, and Pedro between 1948 and2024. Studies published in English only were included, and two reviewers were involved in the data extraction process. RESULTS: Results showed a notable correlation between right-handed individuals and prefrontal cortex lesions with cognition impairment, particularly executive dysfunction, being the most prevalent symptom. Emotional instability followed as the second most common issue, while aphasia remained the primary language deficit. Noninvasive brain stimulation emerged as an effective treatment option for various prefrontal cortex-related disorders. CONCLUSION: Further investigation is needed to understand the mechanism linking handedness to lesion occurrence. Noninvasive brain stimulation should be prioritised for treating prefrontal injuries.

Functional conductivity imaging: quantitative mapping of brain activity.

Theory and modelling suggest that detection of neuronal activity may be feasible using phase sensitive MRI methods. Successful detection of neuronal activity both in vitro and in vivo has been described while others have reported negative results. Magnetic resonance electrical properties tomography may be a route by which signal changes can be identified. Here, we report successful and repeatable detection at 3 Tesla of human brain activation in response to visual and somatosensory stimuli using a functional version of tissue conductivity imaging (funCI). This detects activation in both white and grey matter with apparent tissue conductivity changes of 0.1 S/m (17-20%, depending on the tissue baseline conductivity measure) allowing visualization of complete system circuitry. The degree of activation scales with the degree of the stimulus (duration or contrast). The conductivity response functions show a distinct timecourse from that of traditional fMRI haemodynamic (BOLD or Blood Oxygenation Level Dependent) response functions, peaking within milliseconds of stimulus cessation and returning to baseline within 3-4 s. We demonstrate the utility of the funCI approach by showing robust activation of the lateral somatosensory circuitry on stimulation of an index finger, on stimulation of a big toe or of noxious (heat) stimulation of the face as well as activation of visual circuitry on visual stimulation in up to five different individuals. The sensitivity and repeatability of this approach provides further evidence that magnetic resonance imaging approaches can detect brain activation beyond changes in blood supply.

Personalized whole-brain activity patterns predict human corticospinal tract activation in real-time.

BACKGROUND: Transcranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are therefore needed. METHODS: As a first step towards this goal, we tested a novel machine learning-based EEG-TMS system that identifies personalized brain activity patterns reflecting strong and weak corticospinal tract (CST) output (strong and weak CST states) in healthy adults in real-time. Participants completed a single-session study that included the acquisition of a TMS-EEG-EMG training dataset, personalized classifier training, and real-time EEG-informed single pulse TMS during classifier-predicted personalized CST states. RESULTS: MEP amplitudes elicited in real-time during personalized strong CST states were significantly larger than those elicited during personalized weak and random CST states. MEP amplitudes elicited in real-time during personalized strong CST states were also significantly less variable than those elicited during personalized weak CST states. Personalized CST states lasted for ~1-2 seconds at a time and ~1 second elapsed between consecutive similar states. Individual participants exhibited unique differences in spectro-spatial EEG patterns between personalized strong and weak CST states. CONCLUSION: Our results show for the first time that personalized whole-brain EEG activity patterns predict CST activation in real-time in healthy humans. These findings represent a pivotal step towards using personalized brain state-dependent TMS interventions to promote poststroke CST function.

Aging abolishes circadian rhythms and disrupts temporal organization of antioxidant-prooxidant status, endogenous clock activity and neurotrophin gene expression in the rat temporal cortex.

Disruption of circadian rhythms contributes to deficits in cognitive functions during aging. Up to date, the biochemical, molecular and chronobiological bases of such deterioration have not been completely elucidated. Here, we aim: 1) to investigate the endogenous nature of 24 h-rhythms of antioxidant defenses, oxidative stress, clock's, and neurotrophic factors expression, in the rat temporal cortex (TC), and 2) to study the consequences of aging on the circadian organization of those factors. We observed a circadian organization of antioxidant enzymes activity, lipoperoxidation and the clock, BMAL1 and RORa, proteins, in the TC of young rats. Such temporal organization suggests the existence of a two-way communication among clock transcription factors and antioxidant defenses. This might generate the rhythmic and circadian expression of Bdnf and Rc3 genes involved in the TC-depending cognitive function. Noteworthy, such circadian organization disappears in the TC of aged rats. Aging also reduces glutathione peroxidase activity and expression, and it increases lipid peroxidation, throughout a 24 h-period. An increased oxidative stress makes the cellular redox environment change into an oxidative status which alters the endogenous clock activity and disrupts the circadian organization of, at least part, of the molecular basis of the synaptic plasticity in the TC.

Pregnancy ameliorates neuropathic pain through suppression of microglia and upregulation of the δ-opioid receptor in the anterior cingulate cortex in late-pregnant mice.

PURPOSE: Pregnancy-induced analgesia develops in late pregnancy, but its mechanisms are unclear. The anterior cingulate cortex (ACC) plays a key role in the pathogenesis of neuropathic pain. The authors hypothesized that pregnancy-induced analgesia ameliorates neuropathic pain by suppressing activation of microglia and the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and by upregulating opioid receptors in the ACC in late-pregnant mice. METHODS: Neuropathic pain was induced in non-pregnant (NP) or pregnant (P) C57BL/6JJmsSlc female mice by partial sciatic nerve ligation (PSNL). The nociceptive response was evaluated by mechanical allodynia and activation of microglia in the ACC was evaluated by immunohistochemistry. The expressions of phosphorylated AMPA receptors and opioid receptors in the ACC were evaluated by immunoblotting. RESULTS: In von Frey reflex tests, NP-PSNL-treated mice showed a lower 50% paw-withdrawal threshold than NP-Naïve mice on experimental day 9. No difference in 50% paw-withdrawal threshold was found among the NP-Naïve, NP-Sham, P-Sham, and P-PSNL-treated mice. The number of microglia in the ACC was significantly increased in NP-PSNL-treated mice compared to NP-Sham mice. Immunoblotting showed significantly increased expression of phosphorylated AMPA receptor subunit GluR1 at Ser831 in NP-PSNL-treated mice compared to NP-Sham mice. Immunoblotting also showed significantly increased δ-opioid receptor in the ACC in P-Sham and P-PSNL-treated mice compared to NP-Sham mice. CONCLUSION: Pregnancy-induced analgesia ameliorated neuropathic pain by suppressing activation of microglia and the expression of phosphorylated AMPA receptor subunit GluR1 at Ser831, and by upregulation of the δ-opioid receptor in the ACC in late-pregnant mice.

Anatomical measurements and field modeling to assess transcranial magnetic stimulation motor and non-motor effects.

OBJECTIVE: Explore how anatomical measurements and field modeling can be leveraged to improve investigations of transcranial magnetic stimulation (TMS) effects on both motor and non-motor TMS targets. METHODS: TMS motor effects (targeting the primary motor cortex [M1]) were evaluated using the resting motor threshold (rMT), while TMS non-motor effects (targeting the superior temporal gyrus [STG]) were assessed using a pain memory task. Anatomical measurements included scalp-cortex distance (SCD) and cortical thickness (CT), whereas field modeling encompassed the magnitude of the electric field (E) induced by TMS. RESULTS: Anatomical measurements and field modeling values differed significantly between M1 and STG. For TMS motor effects, rMT was correlated with SCD, CT, and E values at M1 (p < 0.05). No correlations were found between these metrics for the STG and TMS non-motor effects (pain memory; all p-values > 0.05). CONCLUSION: Although anatomical measurements and field modeling are closely related to TMS motor effects, their relationship to non-motor effects - such as pain memory - appear to be much more tenuous and complex, highlighting the need for further advancement in our use of TMS and virtual lesion paradigms.

Cortexa: a comprehensive resource for studying gene expression and alternative splicing in the murine brain.

BACKGROUND: Gene expression and alternative splicing are strictly regulated processes that shape brain development and determine the cellular identity of differentiated neural cell populations. Despite the availability of multiple valuable datasets, many functional implications, especially those related to alternative splicing, remain poorly understood. Moreover, neuroscientists working primarily experimentally often lack the bioinformatics expertise required to process alternative splicing data and produce meaningful and interpretable results. Notably, re-analyzing publicly available datasets and integrating them with in-house data can provide substantial novel insights. However, such analyses necessitate developing harmonized data handling and processing pipelines which in turn require considerable computational resources and in-depth bioinformatics expertise. RESULTS: Here, we present Cortexa-a comprehensive web portal that incorporates RNA-sequencing datasets from the mouse cerebral cortex (longitudinal or cell-specific) and the hippocampus. Cortexa facilitates understandable visualization of the expression and alternative splicing patterns of individual genes. Our platform provides SplicePCA-a tool that allows users to integrate their alternative splicing dataset and compare it to cell-specific or developmental neocortical splicing patterns. All standardized gene expression and alternative splicing datasets can be downloaded for further in-depth downstream analysis without the need for extensive preprocessing. CONCLUSIONS: Cortexa provides a robust and readily available resource for unraveling the complexity of gene expression and alternative splicing regulatory processes in the mouse brain. The data portal is available at https://cortexa-rna.com/.