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Sex differences in mental rotation: top-down versus bottom-up processing.

Functional MRI during performance of a validated mental rotation task was used to assess a neurobiological basis for sex differences in visuospatial processing. Between-sex group analysis demonstrated greater activity in women than in men in dorsalmedial prefrontal and other high-order heteromodal association cortices, suggesting women performed mental rotation in an effortful, "top-down" fashion. In contrast, men activated primary sensory cortices as well as regions involved in implicit learning (basal ganglia) and mental imagery (precuneus), consistent with a more automatic, "bottom-up" strategy. Functional connectivity analysis in association with a measure of behavioral performance showed that, in men (but not women), accurate performance was associated with deactivation of parieto-insular vestibular cortex (PIVC) as part of a visual-vestibular network. Automatic evocation by men to a greater extent than women of this network during mental rotation may represent an effective, unconscious, bottom-up neural strategy which could reasonably account for men's traditional visuospatial performance advantage.

Brain↗

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans↗

Gonadotropin-releasing hormone-induced activation of diacylglycerol kinase-zeta and its association with active c-src.

Gonadotropin-releasing hormone (GnRH)-induced receptor activation has been demonstrated to entrain a wide variety of signaling modalities. Most signaling pathways are concerned with the control of serine, threonine, or tyrosine-protein kinases, however, in the current article we demonstrate that in both a model cell line and in gonadotropes, GnRH additionally mediates the activation of lipid-directed kinases. We have shown that there is a functional connection between protein-tyrosine kinase modulation and lipid kinase activation. In HEK293 cells stably expressing the Type I mammalian GnRH receptor, we employed a proteomic approach to identify novel protein binding partners for GnRH-activated c-Src. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry we identified a GnRH-induced association between c-Src and the lipid kinase, diacylglycerol kinase-zeta (DGK-zeta). Using reciprocal co-immunoprecipitation we show that there is a significant elevation of the association between catalytically active c-Src with DGK-zeta in both HEK293 cells and murine gonadotrope LbetaT2 cells. Employing lipid kinase assays we have shown that the catalytic activity of DGK-zeta is significantly heightened in both HEK293 and LbetaT2 cells by GnRH. In addition, we demonstrate that the activation of DGK-zeta exerts a functional role in the murine gonadotrope LbetaT2 cell line. Elevated expression of DGK-zeta resulted in a shortening of the time scale of ERK activation in these cells suggesting a potential role of endogenous DGK-zeta in controlling the induction of LHbeta transcription by ERK1/2.

Amino Acid Sequence↗

Significance of trigeminal sensory input on regrowth of hypoglossal and facial motoneurons after hypoglossal facial anastomosis in rats.

Hypoglossal facial anastomosis (HFA) is a standard surgical technique for restoration of facial movements in cases of intratemporal lesions of the facial nerve. Case reports provide evidence that an affected trigeminal system reduces functional outcome. In order to detect morphological changes in the hypoglossal nucleus responsible for this phenomenon, we used 18 Wistar rats and performed three different surgical combinations. In group 1, six animals received HFA only. In group 2, HFA was combined with resection of the contralateral infraorbital nerve. In group 3, HFA was combined with resection of the ipsilateral infraorbital nerve. Fifty-six days after the operation, horseradish peroxidase (HRP) was injected into the whisker pad. As shown in previous studies using HRP, retrograde-labelled motoneurons occurred in the hypoglossal and facial nuclei. Counts of the labelled motoneurons showed no change in the number of projecting hypoglossal motoneurons in group 2 when compared to HFA only, but a significantly smaller number in group 3 (-35%). Furthermore, the number of projecting facial motoneurons was significantly reduced in group 2 (-85%) and group 3 (-45%). These morphological findings indicate an absent or insufficient functional connection between the contralateral infraorbital nerve and the hypoglossal nucleus, and a strong influence of the infraorbital nerve to the ipsi- and contralateral facial nuclei. Additionally, our study provides morphological evidence that the integrity of the sensory trigeminal system is very important in reconstructive facial nerve surgery.

Analysis of Variance↗

Functional relationship between MyoD and peroxisome proliferator-activated receptor-dependent regulatory pathways in the control of the human uncoupling protein-3 gene transcription.

Uncoupling protein-3 (UCP3) gene is a member of the mitochondrial carrier superfamily preferentially expressed in skeletal muscle and up-regulated by fatty acids. Peroxisome proliferator-activated receptor (PPAR)alpha and PPARdelta (also known as PPARbeta) mediate human UCP3 gene regulation by fatty acids through a direct-repeat (DR-1) element in the promoter. DR-1 mutation renders UCP3 promoter unresponsive to PPAR ligand in vitro and consistently blocks gene induction by fatty acids in vivo. Although they act through separate sites in the promoter, MyoD and PPAR-dependent regulatory pathways are functionally connected: only in the presence of MyoD, does UCP3 become sensitive to PPAR ligand-dependent regulation. MyoD controls UCP3 promoter activity through a noncanonical Ebox site located in the proximal region, close to transcription initiation site. Moreover, acetylation processes play a crucial role in the control of UCP3 gene regulation. The coactivator p300 protein enhances PPAR ligand-mediated regulation whereas a mutant form devoid of histone acetylase activity blocks the response of the promoter to fatty acids. Conversely, histone deacetylase-1 blunts MyoD-dependent expression of the UCP3 promoter and reduces PPAR-dependent responsiveness. A mutated form of MyoD unable to be acetylated has a lower transactivation capacity on the human UCP3 promoter with respect to wild-type MyoD. It is concluded that MyoD and PPAR-dependent pathways mediate human UCP3 gene regulation and that acetylase activity elicited by coregulators is implicated in the functional interaction between these regulatory pathways. Therefore the convergence of MyoD and PPAR-dependent pathways provides a molecular mechanism for skeletal muscle specificity and fatty acid regulation of human UCP3 gene.

Animals↗

Extending the global workspace theory to emotion: phenomenality without access.

Recent accounts on the global workspace theory suggest that consciousness involves transient formations of functional connections in thalamo-cortico-cortical networks. The level of connectivity in these networks is argued to determine the state of consciousness. Emotions are suggested to play a role in shaping consciousness, but their involvement in the global workspace theory remains elusive. In the present study, the role of emotion in the neural workspace theory of consciousness was scrutinized by investigating, whether unconscious (masked) and conscious (unmasked) display of emotional compared to neutral facial expressions would differentially modulate EEG coherence. EEG coherence was measured by means of computing an average EEG coherence value between the frontal, parietal, and midline scalp sites. Objective awareness checks evidenced that conscious identification of the masked facial expressions was precluded. Analyses revealed reductions in EEG coherence in the lower frequency range for the masked as compared to unmasked neutral facial expressions. Crucially, a decline in EEG coherence was not observed for the emotional facial expressions. In other words, the level of EEG coherence did apparently vary as a function of awareness, but not when emotion was involved. The current finding suggests that EEG coherence is modulated by unconscious emotional processes, which extends common views on the global workspace architecture of consciousness.

Adult↗

Reinnervation of a striated muscle by vagal sensory axons.

Fibres of the sterno-cleido-mastoid (s.c.m.) muscle normally innervated by effects of the accessory nerve have been reinnervated by afferent fibres of the vagus nerve after supranodose vagal-accessory nerve anastomoses or direct implantation of the vagus nerve into the s.c.m. in 58% of the rabbits, 60% of the cats and 75% of sheep in which experiments were performed. Afferents of the vagus growing from cell bodies of the nodose ganglion after severance of central connections can replace the efferent of motor supply to the muscle. Evidence that there was reinnervation of the s.c.m. muscle by vagal afferent fibres was provided from the observations that: (i) electrical stimulations of the anastomosed cervical vagus nerve elicited potentials in the s.c.m. muscle which were abolished by local anaesthesia or final section of the nerve proximal to the site of stimulation; (ii) discharges recorded as bursts of electromyographic potentials occurred during spontaneous movements of larynx, respiratory tract, oesophagus and stomach and on their mechanical or evoked stimulation; and (iii) horseradish peroxidase injected into the reinnervated s.c.m. muscle was detected in somata of ipsilateral nodose ganglia cells. The afferent fibres contributing to the reinnervation were confirmed to be cholinergic as transmission was blocked by gallamine and histochemical evidence obtained of cholinergic motor end-plates. Factors which may have limited the small extent of reinnervation--only one vagal sensory axon out of 600 is able to form functional connections--are discussed.

Animals↗

[p53 mutation and chemoresistance in oral-maxillofacial squamous cell carcinoma. Role of p53 in the cell cycle control and in the modulating action of chemotherapeutic agents].

p53 is a "tumor suppressor gene" with a basic function in the cellular cycle control and subsequently in the induction of the neoplastic process. p53 found changed in the majority of malignant human tumors. In the oral and maxillofacial cancers p53 mutations varies from 4% to 60% of the cases. Researches in vitro in tumors of the colon-rectum, breast, lung, ovary, testicle, bladder and in leukaemia, show a correlation between p53 overexpression (mutation) and resistance to the anti-tumor agents. The functional connection between the p53 and the chemotherapic drugs action which cause a direct DNA damage, is the apoptosis, a physiologic mechanism activated by p53 for regulating cell growth but also indispensable for the cytotoxic effects (apoptosis is an irreversible process culminating in cell death). Loss of the p53 activity (mutation) in the tumoral cells determines non-activation of the apoptosis and the drug resistance. These results have led to early clinical applications. In the breast cancers the p53 is already utilized as chemoresistance marker, directing the therapy, if changed to alternative drugs (Taxolo) which have a p53-independent action. Even into cell lung cancers a retroviral vector containing the wild-type p53 gene was produced to mediate transfer of wild-type p53, noting tumor regression. In oral and maxillofacial tumors surgery is elective. It is emphasized that, in advanced cancers, it is included in multimode protocols where the neoadjuvant chemotherapy has an important clinical function, with precise indications. The possibility to determine previously the p53 "status" in the cancer cells by genetic study, may give a specific factor of screening, indicative of the tumor chemoresponse, together with other well-known prognostic factors, with advantage for the therapeutic programming and especially for the known surgical treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Acute alteration of emotional behaviour in epileptic seizures is related to transient desynchrony in emotion-regulation networks.

OBJECTIVE: During focal epileptic seizures, patients may express intense agitation, screaming and facial expressions of rage, fear or anger. The precise anatomical origin of such intense ictal emotional behaviour is not fully understood and the mechanisms by which the epileptic discharges provoke these phenomena are unknown. In the present study, we analysed the neurophysiological mechanisms underlying ictal emotional behaviour in 3 patients with frontal lobe epilepsies undergoing intracerebral recordings for presurgical evaluation. METHODS: We analyzed the interactions between regions forming 'emotional networks', before and during behavioural alterations. Intracerebral recordings (SEEG method) of seizures from 3 patients presenting with frontal lobe seizures were analyzed. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between brain structures. RESULTS: We found that these intense emotional alterations were associated with a decrease of synchrony between signals recorded from the neural networks known to be involved in emotional processing, and in particular a loss of synchrony between the orbito-frontal cortex and the amygdala. This disruption of functional connections could then result in the disruption of emotional regulation leading to the release of altered behaviour, as observed in epileptic patients during seizures. CONCLUSIONS: We propose that the occurrence of intense ictal emotional behaviour disturbance in frontal lobe seizures is related to a disruption of the normal mechanisms of emotional regulation SIGNIFICANCE: These results provide some insight into our understanding of the pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.

Adult↗

Posttraining inactivation of excitatory afferent input to the locus coeruleus impairs retention in an inhibitory avoidance learning task.

These experiments examined whether the nucleus paragigantocellularis (PGi) contributes to memory storage processing via its ascending excitatory influence on locus coeruleus (LC) neuronal activity. Activation of the LC leads to memory enhancement and also results in a widespread release of norepinephrine in target structures, such as the amygdala and hippocampus. Infusion of norepinephrine into either structure also improves memory for several types of learned responses. Thus, the capacity for norepinephrine to modulate memory within limbic structures may be contingent upon the functional connections between PGi and the LC. To examine this hypothesis, male Sprague-Dawley rats were implanted with cannula aimed above PGi (Experiments 1 and 2) or 1.5 mm dorsal or medial to PGi (Experiment 3). Immediately following inhibitory avoidance training (0.45 mA, 0. 5 s), phosphate-buffered saline, lidocaine (Experiment 1), or 12.5 or 25 nmol/0.5 microl of the GABA agonist muscimol (Experiment 2) was infused into PGi. On a retention test given 48 h later, the latency to reenter the footshock compartment was significantly shorter for subjects given either lidocaine or 12.5 or 25.0 nmol of muscimol compared to controls. In Experiment 3, infusion of lidocaine or muscimol into areas 1.5 mm dorsal or medial to PGi did not significantly alter retention, indicating that the memory impairment observed in Experiments 1 and 2 was site specific and not due to the spread of drug to cell groups surrounding PGi. These findings suggest that PGi may serve a vital function in relaying biologically relevant information to forebrain structures involved in memory via its excitatory influence on the LC.

Anesthetics, Local↗

RBFOX3 regulates hippocampal transcriptomic programs to maintain synaptic and ultrastructural integrity.

RBFOX3 is a neuron-specific RNA-binding protein essential for maintaining brain circuit homeostasis and functional connectivity. Genetic disruptions in RBFOX3 are clinically linked to cognitive impairment, epilepsy, and sleep disorders. Although global Rbfox3 knockout (Rbfox3-/-) mouse models have established its necessity in hippocampus-dependent neuronal circuits and behaviors, the underlying hippocampal transcriptomic landscape and synaptic ultrastructure remain poorly understood. To address these gaps, we integrated hippocampal RNA-sequencing from Rbfox3-/- mice with high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation analysis. We identified 3,401 differentially expressed genes in the hippocampus of Rbfox3-/- mice, confirming 1,920 as candidate RBFOX3 targets. Gene Ontology enrichment analysis revealed that these candidate targets converge on pathways governing neuronal morphogenesis, synaptic transmission, dendritic development, and cognition. Furthermore, transmission electron microscopy of the hippocampal dentate gyrus revealed that while the overall presynaptic area remained unaltered, Rbfox3 deletion reduced presynaptic vesicle number, presynaptic mitochondria area, and postsynaptic density thickness. Collectively, our findings demonstrate that RBFOX3 acts as a critical regulator orchestrating the transcriptomic programs required for hippocampal structural and functional maturation, revealing that its loss compromises both the metabolic and structural architecture of the synapse.

Hippocampus↗

Long-range EEG phase synchronization during an arithmetic task indexes a coherent cortical network simultaneously measured by fMRI.

An open question lies in whether or not distributed activities in the distant brain regions are integrated into a coherent ensemble for cognitive information processing. Long-range phase synchronization is often observed by scalp EEG measurements during cognitive tasks and is considered to provide a possible neural principle for the functional integration of distributed neural activities. Synchronization could be reflected at the neuron firing level or at the local field potential and could appear in the scalp EEG under certain conditions on neural spatial and temporal coherence. To examine if phase synchronization is concerned with the integration of distant regions, we proposed a method to extract brain activities associated with task-dependent phase synchronization by combining simultaneous fMRI and EEG. By applying this method in a mental arithmetic task, we found a dominant task-dependent increase of phase synchronization around 14 Hz (in beta frequency) across bilateral parietal sites that were associated with both negative and positive BOLD responses. Functional connectivity analyses of these regions demonstrated that an increase in hemispheric beta synchronization was associated with a linking between the cross-hemispheric regions (left angular gyrus and right superior parietal gyrus) and also among the anterior-posterior regions (right dorsolateral prefrontal cortex, putamen, and right superior temporal gyrus). These findings indicate that the positive BOLD regions (dorsolateral prefrontal cortex and superior parietal lobule) are linked with other negative BOLD regions. We also discussed the possible importance of beta synchronization in the formation of a working memory network.

Adult↗

A physiological measure of shifting connections in the Rana pipiens retinotectal system.

The retinotectal connections of developing Rana tadpoles and froglets have been studied using light-pipe techniques to directly assay the pattern of the projection from the retina to the tectum. The projection site of the retina surrounding the optic nerve head was determined at two different stages of development (late larval and metamorphic frog) on the same animal. Small electrolytic marker lesions were used to mark the tectal sites to which the optic nerve head projected at these two times. Comparison of the positions of the two lesions gives a direct measure of the shift in the projection during the interlesion time interval of one week. The results indicate a shift in the projection of 275 micron week-1 in late larval life. Previous work in Xenopus using the light-pipe techniques indicated a qualitatively similar shift during equivalent stages of development, but significantly smaller in magnitude. In the present study, topographic postsynaptic units could be recorded at all stages investigated, indicating functional synapses between the optic nerve fibres and the tectum. Thus, these studies offer evidence of a significant shift in the functional connection pattern of the amphibian retinotectal map during development, in agreement with the recent anatomical data from other laboratories on the Rana and goldfish visual system.

Animals↗

Rapid activity-dependent sprouting of optic fibers into a local area denervated by application of beta-bungarotoxin in goldfish tectum.

The retinotectal projection is known to be capable of extensive long-term expansion of connections, but it is not known how fast such changes can occur or what triggers sprouting of terminals. We studied sprouting of optic fibers into an area denervated by local microinjection of beta-bungarotoxin (beta-BTX), a specific presynaptic neurotoxin with phospholipase A2 activity that destroys nerve terminals at the neuromuscular junction. After injection of 0.1 pmol of beta-BTX, the optic terminals fired spontaneously with decreasing amplitude and became silent within 1 to 2 h. Outside the injection zone, the retinotectal map was normal, so the silent zone was associated with a scotoma in the visual field. Horseradish peroxidase (HRP) staining of the entire optic nerve showed a denervated region at the injection site with beaded, degenerating fibers at its edge. Between 3 and 9 days later, optic units were recorded within the injection zone whose receptive fields lay just outside the scotoma in the visual field, indicating that intact surrounding terminals had sprouted into the area. These sprouts made functional connections, as indicated by field potential recordings and current source-density analysis. At this time, HRP staining also demonstrated retinal innervation within the injection zone. By 12 days, normal maps with no scotoma were recorded and HRP staining was normal at the injection site, indicating that the beta-BTX-damaged fibers had regenerated to reclaim their tectal sites. The results show that the retinotectal projection of goldfish is very dynamic, since intact optic fibers can sprout into adjacent vacant postsynaptic territory within 2 to 3 days, much faster than previously reported. In a final experiment, we showed that this sprouting is activity-dependent, since it could be prevented by blocking retinal activity with intraocular tetrodotoxin (TTX) during the first 2 days postinjection, even though TTX block of activity does not block regeneration in this system. One possible mechanism for this rapidly triggered sprouting is that arachidonic acid liberated by beta-BTX acts as a sprouting factor to attract surrounding healthy fibers into the denervated region but requires activity at the terminals to be effective.

Animals↗

Dynamic changes in corticospinal tracts after stroke detected by fibretracking.

BACKGROUND AND AIMS: The integrity of motor pathways and functional connectivity patterns are important in assessing plastic changes related to successful recovery, to obtain prognostic information and to monitor future therapeutic strategies of stroke patients. We tested the following hypotheses: (1) that changes in axonal integrity along the corticospinal tract after stroke can be detected as a reduction in fractional anisotropy; and (2) that sustained low fractional anisotropy is indicative of axonal loss and therefore is correlated with poor motor outcome, as measured by specific neurological motor scores. METHODS: We developed a segmentation tool based on magnetic resonance diffusion tensor imaging in conjunction with three dimensional fibretracking for longitudinal studies of the corticospinal tract, and used specific neurological motor scores to test the hypotheses in five stroke patients within the first week and 30 and 90 days after the stroke. RESULTS: Reduction in fractional anisotropy within the first weeks after stroke reflected a decline in axonal integrity, leading to Wallerian degeneration, and demonstrated a correlation between the temporal evolution of fractional anisotropy and motor function in patients with poor motor outcome. CONCLUSION: The study demonstrated the feasibility of fibretracking as a segmentation tool for mapping distal parts of the corticospinal motor pathways and showed that fractional anisotropy in the segmented corticospinal tract is a sensitive measure of structural changes after stroke.

Aged↗

Strategies to create a regenerating environment for the injured spinal cord.

Spine cord injury (SCI) leads to devastating functional loss below the level of injury. Partially explained by the presence of a non-permissive environment, the injured spinal cord does not mount adequate regeneration to re-establish functional connections. Therefore, it is important to identify the cellular and molecular factors and their interactions that affect axonal regeneration within the changed environment. This review will discuss the current understanding of the neuronal and glial factors and the extracellular matrix in the spinal cord that inhibit axonal growth, and it will summarize some major approaches for facilitation of regeneration. The strategies are classified into the following categories: penetration of the blood-brain barrier; modulation of caspase activity to reduce apoptosis; stem cells and tissue implantation; administration of neurotrophic factors, including viral vector-mediated delivery; and modulation of the extracellular matrix. Although recent studies on genomic regulation and apoptosis have identified particularly important molecular targets, more is necessary to achieve long-term regeneration. A combination of the approaches targeting various aspects in the regenerating environment would be more effective than a single strategy. Overall, insights arising from the experimental results may eventually lead to better therapeutic intervention so as to lessen the functional disability and enhance the quality of life in patients with SCI.

Animals↗

Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA.

Grb2 is an adaptor molecule comprising one Src homology (SH) 2 and two SH3 domains. This protein has a natural isoform named Grb3-3 with a deletion within the SH2 domain. Numerous evidence points to a functional connection between SH2- and SH3-containing proteins and molecules implicated in RNA biogenesis. In this context, we have examined the binding of Grb2 and Grb3-3 to heterogeneous nuclear ribonucleoprotein (hnRNP) C. By the use of an in vivo genetic approach and through in vitro experiments, we furnish evidence that both Grb2 and Grb3-3 interact with hnRNP C proteins. Subcellular fractionation studies clearly show that Grb2 is partially localized in the nucleus. In addition, coimmunoprecipitation experiments demonstrate that Grb2.hnRNP C complexes exist in intact hematopoietic cells. The carboxyl-terminal SH3 domains of Grb2 and Grb3-3 are primarily responsible for the association with hnRNP C. However, although the proline-rich motif of hnRNP C is involved in the interaction with Grb2, it is not in the binding to Grb3-3. Furthermore, poly(U) RNA inhibits the association of Grb2 with hnRNP C, whereas it enhances the interaction between Grb3-3 and hnRNP C. These findings suggest that the Grb2/Grb3-3-hnRNP C interactions might fulfill different biological functions.

3T3 Cells↗

Basal ganglia involvement in memory-guided movement sequencing.

The basal ganglia (BG) are thought to play a critical role in motor planning and movement sequencing. While electrophysiological and imaging studies have shown that the dorso-lateral prefrontal cortex (DLPFC) is involved in working memory (WM), the involvement of the BG in this process is not well understood. We used a motor sequencing task to investigate the differential role of BG nuclei in memory-guided movement. Significant activation was observed in the DLPFC and posterior putamen and globus pallidus (GP), with a trend in the caudate and no differences in the anterior putamen. We then investigated the effect of BG outflow on thalamic activation using functional connectivity analysis. Activation in the posterior putamen + GP was found to be correlated with thalamic activation only in the hemisphere contralateral to movement. These results provide the first fMRI evidence that the BG may modulate activity in the thalamus during working memory-guided movement sequencing. Our findings suggest that the BG activation may reflect increased motor sequencing demands during the memory-guided movement condition and, specifically, that the posterior putamen and GP may play a role in maintenance of representations in WM in a manner that contributes to planning and temporal organization of motor sequencing.

Adult↗