GABAB receptors-mediated tonic inhibition of glutamate release from A\u3b2 fibers in rat laminae III/IV of the spinal cord dorsal horn.

Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on A\u3b2 fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission. We performed high-resolution electron microscopic analysis, showing that GABAB2 subunit is expressed on 71.9% of terminals in rat lamina III-IV. These terminals were engaged in axodendritic synapses and, for the 46%, also expressed glutamate immunoreactivity. Monosynaptic excitatory postsynaptic currents, evoked by A\u3b2 fiber stimulation and recorded from lamina III/IV neurons in spinal cord slices, were strongly depressed by application of baclofen (0.1-2.5\u2009\ub5M), acting as a presynaptic modulator. Application of the GABABR antagonist CGP 55845 caused, in a subpopulation of neurons, the potentiation of the first of two excitatory postsynaptic currents recorded with the paired-pulse protocol, showing that GABABRs are endogenously activated. A decrease in the paired-pulse ratio accompanied the effect of CGP 55845, implying the involvement of presynaptic GABABRs. CGP 55845 facilitated only the first excitatory postsynaptic current also during a train of four consecutive stimuli applied to A\u3b2 fibers. These results suggest that GABABRs tonically inhibit glutamate release from A\u3b2 fibers at a subset of synapses in deep dorsal horn. This modulation specifically affects only the early phase of synaptic excitation in lamina III-IV neuron

Influence of Attention Control on Implicit and Explicit Emotion Processing of Face and Body: Evidence From Flanker and Same-or-Different Paradigms

Many existing findings indicate that processing of emotional information is pre-attentive, largely immune from attentional control. Nevertheless, inconsistent evidence on the interference of emotional cues on cognitive processing suggests that this influence may be a highly conditional phenomenon. The aim of the present study was twofold: (1) to examine the modulation of attention control on emotion processing using facial expressions (2) explore the very same effect for emotional body expressions. In Experiment 1, participants performed a Flanker task in which they had to indicate either the emotion (happy/fearful) or the gender of the target stimulus while ignoring the distracting stimuli at the side. We found evidence for intrusion of the emotional dimension of a stimulus in both the emotion and gender discrimination performance, thus when either task-relevant or task-irrelevant. To further explore the influence of attention control mechanisms, in Experiment 2 participants performed a same-or-different judgment task in which they were asked to pay attention to both the central and lateral stimuli and indicated whether the central stimulus matched the lateral for emotion or gender. Results showed that emotional features exerted an influence at an implicit level (i.e., during gender judgments) for bodies only. Gender features did not affect emotional processing in either experiments. To rule out the possibility that this effect was driven by postural rather than emotional features of fearful vs. happy stimuli, a control experiment was conducted. In Experiment 3, bodies with an opening/up-ward or closing/down-ward posture but with no emotional valence were presented. Results revealed that the body posture did not influence gender discrimination. Findings suggest that the emotional valence of a face or body stimulus can overpass attention filtering mechanisms, independently from the level of attentional modulation (Experiment 1). However, broadening the focus of attention to include the lateral stimuli led emotional information to intrude on the main task, exerting an implicit, bottom–up influence on gender processing, only when conveyed by bodies (Experiment 2). Results point to different mechanisms for the implicit processing of face and body emotional expressions, with the latter likely having role on action preparation processes

Body Processing in Children and Adolescents with Traumatic Brain Injury: An Exploratory Study

Dysfunctions in body processing have been documented in adults with brain damage, while limited information is available for children. This study aimed to investigate body processing in children and adolescents with traumatic brain injury (TBI) (N = 33), compared to peers with typical development. Two well-known computerized body-representation paradigms, namely Visual Body Recognition and Visuo-spatial Imagery, were administered. Through the first paradigm, the body inversion and composite illusion effects were tested with a matching to sample task as measures of configural and holistic processing of others’ bodies, respectively. The second paradigm investigated with a laterality judgement task the ability to perform first-person and object-based mental spatial transformations of own body and external objects, respectively. Body stimuli did not convey any emotional contents or symbolic meanings. Patients with TBI had difficulties with mental transformations of both body and object stimuli, displaying deficits in motor and visual imagery abilities, not limited to body processing. Therefore, cognitive rehabilitation of body processing in TBI might benefit from the inclusion of both general training on visuo-spatial abilities and specific exercises aimed at boosting visual body perception and motor imagery

Home-based cognitive training in pediatric patients with acquired brain injury: preliminary results on efficacy of a randomized clinical trial

Cognitive rehabilitation may compensate for cognitive deficits of children with acquired brain injury (ABI), capitalizing on the use-dependent plasticity of a developing brain. Remote computerized cognitive training (CCT) may be delivered to patients in ecological settings, ensuring rehabilitation continuity. This work evaluated cognitive and psychological adjustment outcomes of an 8-week multi-domain, home-based CCT (Lumosity Cognitive Training) in a sample of patients with ABI aged 11–16 years. Two groups of patients were engaged in five CCT sessions per week for eight weeks (40 sessions). According to a stepped-wedge research design, one group (Training-first Group) started the CCT immediately, whereas the other group (Waiting-first Group) started the CCT after a comparable time of waiting list. Changes after the training and after the waiting period were compared in the two groups. Both groups improved in visual-spatial working memory more after the training than after the waiting-list period. The Training-first group improved also in arithmetic calculation speed. Findings indicate that a multi-domain CCT can produce benefits in visual-spatial working memory, probably because, in accordance with previous research, computer games heavily tax visuo-spatial abilities. This suggests that the prolonged stimulation of the same cognitive ability may generate the greatest benefits in children with ABI

Development of nociceptive synaptic inputs to the neonatal rat dorsal horn: glutamate release by capsaicin and menthol

To study the postnatal development of nociceptive synaptic inputs in the superficial dorsal horn of the neonatal rat spinal cord, we examined the effect of capsaicin and menthol on glutamatergic mEPSCs in postnatal day (P) 0-1, P5-6 and P9-11 slices of spinal cord. Capsaicin (100 nM to 2 muM) increased the mEPSC frequency in a concentration-dependent manner at all ages tested, with a significant enhancement of the effect between P5 and P10. This effect was sensitive to vanilloid receptor (VR) antagonists. The elevation in mEPSC frequency occurred at concentrations of capsaicin (100 nM) that did not alter the distribution of mEPSC amplitudes and was abolished by a dorsal rhizotomy, demonstrating that capsaicin acts via presynaptic VR1 receptors localized on primary afferents. Menthol significantly increased the mEPSC frequency with a similar developmental pattern to capsaicin without consistently affecting mEPSC amplitude. The increase in mEPSC frequency following capsaicin did not depend on transmembrane calcium influx since it persisted in zero [Ca2+](o). The facilitation of spontaneous glutamate release by capsaicin was sufficient to evoke action potentials in neonatal dorsal horn neurons but was accompanied by a block of EPSCs evoked by electrical stimulation of the dorsal root. These results indicate that VR1-expressing nociceptive primary afferents; form functional synaptic connections in the superficial dorsal horn from birth and that activation of the VR1 receptor increases spontaneous glutamate release via an undetermined mechanism. In addition, the data suggest that immature primary afferents express functional menthol receptors that are capable of modulating transmitter release. These results have important functional implications for infant pain processing

Fragile X mental retardation protein (FMRP) and metabotropic glutamate receptor subtype 5 (mGlu5) control stress granule formation in astrocytes

Fragile X syndrome (FXS) is a common form of intellectual disability and autism caused by the lack of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA transport and protein synthesis. Upon cellular stress, global protein synthesis is blocked and mRNAs are recruited into stress granules (SGs), together with RNA-binding proteins including FMRP. Activation of group-I metabotropic glutamate (mGlu) receptors stimulates FMRP-mediated mRNA transport and protein synthesis, but their role in SGs formation is unexplored. To this aim, we pre-treated wild type (WT) and Fmr1 knockout (KO) cultured astrocytes with the group-I-mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) and exposed them to sodium arsenite (NaAsO2), a widely used inducer of SGs formation. In WT cultures the activation of group-I mGlu receptors reduced SGs formation and recruitment of FMRP into SGs, and also attenuated phosphorylation of eIF2α, a key event crucially involved in SGs formation and inhibition of protein synthesis. In contrast, Fmr1 KO astrocytes, which exhibited a lower number of SGs than WT astrocytes, did not respond to agonist stimulation. Interestingly, the mGlu5 receptor negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine (MPEP) antagonized DHPG-mediated SGs reduction in WT and reversed SGs formation in Fmr1 KO cultures. Our findings reveal a novel function of mGlu5 receptor as modulator of SGs formation and open new perspectives for understanding cellular response to stress in FXS pathophysiology

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Telepsychotherapy with children and families: Lessons gleaned from two decades of translational research

This is the author accepted manuscript. The final version is available from the American Psychological Association via the DOI in this recordThe novel coronavirus, COVID-19, has led to sweeping changes in psychological practice and the concomitant rapid uptake of telepsychotherapy. Although telepsychotherapy is new to many clinical psychologists, there is considerable research on telepsychotherapy treatments. Nearly two decades of clinical research on telepsychotherapy treatments with children with neurological conditions has the potential to inform emerging clinical practice in the age of COVID-19. Toward that end, we synthesized findings from 14 clinical trials of telepsychotherapy problemsolving and parent training interventions involving more than 800 children and families with diverse diagnoses including traumatic brain injury, epilepsy, brain tumors, congenital heart disease, and perinatal stroke. We summarize efficacy across studies and clinical populations and report feasibility and acceptability data from the perspectives of parents, children, and therapists. We describe adaptation for international contexts and strategies for troubleshooting technological challenges and working with families of varying socioeconomic strata. The extensive research literature reviewed and synthesized provides considerable support for the utility of telepsychotherapy with children with neurological conditions and their families and underscores its high level of acceptability with both diverse clinical populations and providers. During this period of heightened vulnerability and stress and reduced access to usual supports and services, telepsychotherapy approaches such as online family problem-solving treatment and online parenting skills training may allow psychologists to deliver traditional evidence-based treatments virtually while preserving fidelity and efficacyNational Institute for Health Research (NIHR

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

<p>Abstract</p> <p>Background</p> <p>Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR) system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1) if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2) if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR.</p> <p>The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP) in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO₂laser heat pulses.</p> <p>Results</p> <p>While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different.</p> <p>Conclusion</p> <p>Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.</p