Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation.

The mammalian primary visual cortex (V1) is especially susceptible to changes in visual input over a well-defined critical period, during which closing one eye leads to a loss of responsiveness of neurons to the deprived eye and a shift in response toward the open eye. This functional plasticity can occur rapidly, following even a single day of eye closure, although the structural bases of these changes are unknown. Here, we show that rapid structural changes at the level of dendritic spines occur following brief monocular deprivation. These changes are evident in the supra- and infragranular layers of the binocular zone and can be mimicked by degradation of the extracellular matrix with the tPA/plasmin proteolytic cascade. Further, monocular deprivation occludes a subsequent effect of matrix degradation, suggesting that this mechanism is active in vivo to permit structural remodeling during ocular dominance plasticity.

Using Patient Feedback to Optimize the Design of a Certolizumab Pegol Electromechanical Self-Injection Device: Insights from Human Factors Studies.

INTRODUCTION: We incorporated patient feedback from human factors studies (HFS) in the patient-centric design and validation of ava®, an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab pegol (CZP). METHODS: Healthcare professionals, caregivers, healthy volunteers, and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or Crohn's disease participated in 11 formative HFS to optimize the e-Device design through intended user feedback; nine studies involved simulated injections. Formative participant questionnaire feedback was collected following e-Device prototype handling. Validation HFS (one EU study and one US study) assessed the safe and effective setup and use of the e-Device using 22 predefined critical tasks. Task outcomes were categorized as "failures" if participants did not succeed within three attempts. RESULTS: Two hundred eighty-three participants entered formative (163) and validation (120) HFS; 260 participants performed one or more simulated e-Device self-injections. Design changes following formative HFS included alterations to buttons and the graphical user interface screen. All validation HFS participants completed critical tasks necessary for CZP dose delivery, with minimal critical task failures (12 of 572 critical tasks, 2.1%, in the EU study, and 2 of 5310 critical tasks, less than 0.1%, in the US study). CONCLUSION: CZP e-Device development was guided by intended user feedback through HFS, ensuring the final design addressed patients' needs. In both validation studies, participants successfully performed all critical tasks, demonstrating safe and effective e-Device self-injections. FUNDING: UCB Pharma. Plain language summary available on the journal website.

Modification of sudden onset auditory ERP by involuntary attention to visual stimuli.

To investigate the cross-modal nature of the exogenous attention system, we studied how involuntary attention in the visual modality affects ERPs elicited by sudden onset of events in the auditory modality. Relatively loud auditory white noise bursts were presented to subjects with random and long inter-trial intervals. The noise bursts were either presented alone, or paired with a visual stimulus with a visual to auditory onset asynchrony of 120 ms. In a third condition, the visual stimuli were shown alone. All three conditions, auditory alone, visual alone, and paired visual/auditory, were randomly inter-mixed and presented with equal probabilities. Subjects were instructed to fixate on a point in front of them without task instructions concerning either the auditory or visual stimuli. ERPs were recorded from 28 scalp sites throughout every experimental session. Compared to ERPs in the auditory alone condition, pairing the auditory noise bursts with the visual stimulus reduced the amplitude of the auditory N100 component at Cz by 40% and the auditory P200/P300 component at Cz by 25%. No significant topographical change was observed in the scalp distributions of the N100 and P200/P300. Our results suggest that involuntary attention to visual stimuli suppresses early sensory (N100) as well as late cognitive (P200/P300) processing of sudden auditory events. The activation of the exogenous attention system by sudden auditory onset can be modified by involuntary visual attention in a cross-model, passive prepulse inhibition paradigm.

Effects of synaptic activity on dendritic spine motility of developing cortical layer v pyramidal neurons.

It is increasingly clear that dendritic spines play an important role in compartmentalizing post-synaptic signals and that their dynamic morphological properties have functional consequences. Here, we examine this issue using two-photon microscopy to characterize spine motility on layer V pyramidal neurons in acute slices of the developing mouse cortex. In this system, all spine classes except filopodia become less dynamic as development proceeds. General manipulations of activity (TTX or KCl treatment) do not alter spine dynamics, although increased glutamatergic transmission (AMPA or NMDA treatment) stabilizes developing cortical spines. These effects on spine dynamics do not appear to be related to AMPA or NMDA receptor expression as assessed with immunolabeling, as there is no correlation between spine motility and AMPA (GluR1/2) or NMDA (NR1/NR2B) receptor subunit expression on a spine by spine basis. These results indicate that activity through glutamatergic synapses is important for regulating spine motility in the developing mouse cortex, and that the relative complement of receptors, while different across morphological classifications, cannot account for differences in dynamic structural changes in dendritic spines.