Petites cellules excitables deviendront grandes : le rythme pour la raison.

International audienc

Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells

BACKGROUND: Because of the importance of voltage-activated K(+) channels during embryonic development and in cell proliferation, we present here the first description of these channels in E15 rat embryonic neural progenitor cells derived from the subventricular zone (SVZ). Activation, inactivation, and single-channel conductance properties of recorded progenitor cells were compared with those obtained by others when these Kv gene products were expressed in oocytes. METHODOLOGY/PRINCIPAL FINDINGS: Neural progenitor cells derived from the subventricular zone of E15 embryonic rats were cultured under conditions that did not promote differentiation. Immunocytochemical and Western blot assays for nestin expression indicated that almost all of the cells available for recording expressed this intermediate filament protein, which is generally accepted as a marker for uncommitted embryonic neural progenitor cells. However, a very small numbers of the cells expressed GFAP, a marker for astrocytes, O4, a marker for immature oligodendrocytes, and betaIII-tubulin, a marker for neurons. Using immunocytochemistry and Western blots, we detected consistently the expression of Kv2.1, and 4.3. In whole-cell mode, we recorded two outward currents, a delayed rectifier and an A-type current. CONCLUSIONS/SIGNIFICANCE: We conclude that Kv2.1, and 4.3 are expressed in E15 SVZ neural progenitor cells, and we propose that they may be associated with the delayed-rectifier and the A-type currents, respectively, that we recorded. These results demonstrate the early expression of delayed rectifier and A-type K(+) currents and channels in embryonic neural progenitor cells prior to the differentiation of these cells

Biological predictors of suicidality in schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65166/1/j.1600-0447.1996.tb09883.x.pd

Familial influences on the clinical characteristics of major depression: a twin study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66157/1/j.1600-0447.1992.tb03283.x.pd

Sensory Transduction Channel Subunits, tax-4 and tax-2, Modify Presynaptic Molecular Architecture in C. elegans

During development, neural activity is important for forming proper connections in neural networks. The effect of activity on the gross morphology and synaptic strength of neurons has been well documented, but little is known about how activity affects different molecular components during development. Here, we examine the localization of four fluorescently-tagged presynaptic proteins, RAB-3, SNG-1/synaptogyrin, SYD-2/Liprin-α, and SAD-1/SAD kinase, in the C. elegans thermosensory neuron AFD. We show that tax-4 and tax-2, two genes that encode the cyclic nucleotide-gated channel necessary for sensory transduction in AFD, disrupt the localization of all four proteins. In wild-type animals, the synaptic vesicle (SV) markers RAB-3 and SNG-1 and the active zone markers SYD-2 and SAD-1 localize in a stereotyped, punctate pattern in the AFD axon. In tax-4 and tax-2 mutants, SV and SYD-2 puncta are more numerous and less intense. Interestingly, SAD-1 puncta are also less intense but do not increase in number. The change in puncta number can be rescued cell-autonomously in AFD. These results suggest that sensory transduction genes tax-4 and tax-2 are necessary for the proper assembly of presynapses

Disordered semantic representation in schizophrenic temporal cortex revealed by neuromagnetic response patterns

BACKGROUND: Loosening of associations and thought disruption are key features of schizophrenic psychopathology. Alterations in neural networks underlying this basic abnormality have not yet been sufficiently identified. Previously, we demonstrated that spatio-temporal clustering of magnetic brain responses to pictorial stimuli map categorical representations in temporal cortex. This result has opened the possibility to quantify associative strength within and across semantic categories in schizophrenic patients. We hypothesized that in contrast to controls, schizophrenic patients exhibit disordered representations of semantic categories. METHODS: The spatio-temporal clusters of brain magnetic activities elicited by object pictures related to super-ordinate (flowers, animals, furniture, clothes) and base-level (e.g. tulip, rose, orchid, sunflower) categories were analysed in the source space for the time epochs 170–210 and 210–450 ms following stimulus onset and were compared between 10 schizophrenic patients and 10 control subjects. RESULTS: Spatio-temporal correlations of responses elicited by base-level concepts and the difference of within vs. across super-ordinate categories were distinctly lower in patients than in controls. Additionally, in contrast to the well-defined categorical representation in control subjects, unsupervised clustering indicated poorly defined representation of semantic categories in patients. Within the patient group, distinctiveness of categorical representation in the temporal cortex was positively related to negative symptoms and tended to be inversely related to positive symptoms. CONCLUSION: Schizophrenic patients show a less organized representation of semantic categories in clusters of magnetic brain responses than healthy adults. This atypical neural network architecture may be a correlate of loosening of associations, promoting positive symptoms

Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system

Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression

BACKGROUND: Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. METHODS: Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. RESULTS: Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. CONCLUSION: The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features

Group cognitive behavioural therapy for women with depression: pilot and feasibility study for a randomised controlled trial using mixed methods

<p>Abstract</p> <p>Background</p> <p>Group Cognitive Behavioural Therapy (CBT) may provide a means of improving mental health among people with depression but few studies have explored its effectiveness. Our aim was to examine the feasibility and acceptability of a randomised controlled trial of a group intervention based on CBT principles for women with depression in primary care.</p> <p>Methods</p> <p>Women aged 30 to 55 years were recruited and randomly assigned to either 12 weeks of the group intervention or usual care (control). The group intervention was based on a manual and used CBT and problem solving principles with weekly topics including raising activity levels, spotting and catching negative thoughts, problem solving and relaxation. Women were recruited from deprived areas of Bristol. The groups were run by facilitators with some experience and background in group work and one weeks training in use of the course manual. Assessments of mental health were made using measures including the PHQ-9. Follow-up was at 3 and 6 months after the intervention. Qualitative methods were used to support the design of the intervention and to help understand issues of acceptability and feasibility. Interviews were conducted with all participants at baseline and at 3 and 6 months although detailed qualitative analysis was based on a purposive sample of 20 participants at the 3 time points.</p> <p>Results</p> <p>Of the 86 participants assessed for eligibility, 52 were allocated to the intervention arm and 21 to the control group. The intervention was delivered according to the manual despite the limited training of the facilitators. The intervention was received favourably by participants and facilitators, with good attendance at sessions for those who engaged with the intervention. Follow up rates at 3 and 6 months for women in both the intervention and control arms were also good. The trial methodology used was appropriate and feasible.</p> <p>Conclusions</p> <p>This study showed that a randomised controlled trial of group CBT for women with depression is feasible and the intervention is acceptable, and may possibly prove to be effective in a larger trial. The cost effectiveness of group CBT for depression should be explored further in a full trial.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00663078">NCT00663078</a></p

Computerised cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: external pilot trial

<p>Abstract</p> <p>Background</p> <p>People with multiple sclerosis (MS) are at high risk of depression. We undertook a pilot trial of computerised cognitive behavioural therapy (CCBT) for the treatment of depression in people with MS to test the feasibility of undertaking a full trial.</p> <p>Methods</p> <p>Participants with a diagnosis of MS and clinical levels of depression were recruited through out-patient clinics and postal screening questionnaires at two UK centres and randomised to CCBT or usual care. Clinical outcomes included the Beck Depression Inventory (BDI-II) and Multiple Sclerosis Impact Scale (MSIS-29) at baseline, 8 and 21 weeks. Feasibility outcomes included: recruitment rate; reasons for refusal, withdrawal and dropout; feasibility and acceptability of the proposed outcome measures; sample size estimation and variation in and preferences for service delivery.</p> <p>Results</p> <p>Twenty-four participants were recruited. The recruitment rate, calculated as the proportion of those invited to fill in a screening questionnaire who were consented into the trial, was 4.1%. Recruitment through out-patient clinics was somewhat slower than through screening questionnaire mail-out but the overall recruitment yield was similar. Of the 12 patients in the CCBT arm, 9 (75%) completed at least four, and 6 completed all 8 CCBT sessions. For completers, the median time (IQR) to complete all eight CCBT sessions was 15 (13 to 20) weeks. Participants expressed concern about the face validity of the Beck Depression Inventory II for the measurement of self-reported depression in people with MS. The MSIS-29 was the patient-reported outcome measure which participants felt best reflected their concerns. The estimated sample size for a full trial is between 180 and 390 participants. NHS partners were not delivering CCBT in community facilities and participants preferred to access CCBT at home, with no one expressing a preference for use of CCBT in an alternative location.</p> <p>Conclusions</p> <p>A definitive trial, with a recruitment window of one year, would require the participation of around 13 MS centres. This number of centres could be reduced by expanding the eligibility criteria to include either other neurological conditions or people with more severe depression. The MSIS-29 should be used as a patient-important outcome measurement.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN81846800">ISRCTN81846800</a></p