SUMMARY Motile dendritic filopodial processes are thought to be precursors of spine synapses, but how motility relates to cell-surface cues required for axon-dendrite recognition and synaptogenesis remains unclear. We demonstrate with dynamic imaging that loss of EphBs results in reduced motility of filopodia in cultured cortical neurons and brain slice. EphB knockdown and rescue experiments during different developmental time windows show that EphBs are required for synaptogenesis only when filopodia are most abundant and motile. In the context of EphB knockdown and reduced filopodia motility, independent rescue of either motility with PAK or of Ephephrin binding with an EphB2 kinase mutant is not sufficient to restore synapse formation. Strikingly, the combination of PAK and kinase-inactive EphB2 rescues synaptogenesis. Deletion of the ephrin-binding domain from EphB2 precludes rescue, indicating that both motility and trans-cellular interactions are required. Our findings provide a mechanistic link between dendritic filopodia motility and synapse differentiation.

Dynamic regulation of the localization and function of N-methyl-D-aspartate receptors (NMDARs) is critical for synaptic development and function. The composition and localization of NMDAR subunits at synapses are tightly regulated, and can influence the ability of individual synapses to undergo long-lasting changes in response to stimuli. Here we examine mechanisms by which EphB2, a receptor tyrosine kinase that binds and phosphorylates NMDARs, controls NMDAR subunit localization and function at synapses. We find that in mature neurons, EphB2 expression levels regulate the amount of NMDARs at synapses, and EphB activation decreases Ca2+-dependent desensitization of NR2B-containing NMDARs. EphBs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple EphB knockout mice lacking EphB1-3 exhibit homeostatic upregulation of NMDAR surface expression and loss of proper targeting to synaptic sites. These findings demonstrate that in the mature nervous system, EphBs are key regulators of the synaptic localization of NMDARs.

BackgroundPatients with deep brain stimulation (DBS) implants have limited access to MRI due to safety concerns associated with RF‐induced heating. Currently, MRI in these patients is allowed in 1.5T horizontal bore scanners utilizing pulse sequences with reduced power. However, the use of 3T MRI in such patients is increasingly reported based on limited safety assessments. Here we present the results of comprehensive RF heating measurements for two commercially available DBS systems during MRI at 1.5T and 3T.PurposeTo assess the effect of imaging landmark, DBS lead configuration, and patient's body composition on RF heating of DBS leads during MRI at 1.5T and 3T.Study TypePhantom and ex vivo study.Population/Subjects/Phantom/Specimen/Animal ModelGel phantoms and cadaver brain.Field Strength/Sequence1.5T and 3T, T1‐weighted turbo spin echo.AssessmentRF heating was measured at the tips of DBS leads implanted in brain‐mimicking gel. Image artifact was assessed in a cadaver brain implanted with an isolated DBS lead.Statistical TestsDescriptive.ResultsWe observed substantial fluctuation in RF heating, mainly affected by phantom composition and DBS lead configuration, ranging from 0.14°C to 23.73°C at 1.5T, and from 0.10°C to 7.39°C at 3T. The presence of subcutaneous fat substantially altered RF heating at the electrode tips (3.06°C < ∆T < 19.05° C). Introducing concentric loops in the extracranial portion of the lead at the surgical burr hole reduced RF heating by up to 89% at 1.5T and up to 98% at 3T compared to worst‐case heating scenarios.Data ConclusionDevice configuration and patient's body composition substantially altered the RF heating of DBS leads during MRI. Interestingly, certain lead trajectories consistently reduced RF heating and image artifact.Level of Evidence 1Technical Efficacy Stage 1J. MAGN. RESON. IMAGING 2021;53:599–610.

Based on extracellular recordings from 69 lateral geniculate nucleus (LGN) cells in the anesthetized cat, we found spatial summation within their receptive fields to be dependent on the contrast of the stimuli presented. By fitting the summation curves to a difference of Gaussians model, we attributed this contrast-dependent effect to an actual change in the size of the center mechanism. Analogous changes in spatial frequency tuning were also observed, specifically increased peaks and cut-off frequencies with contrast. These effects were seen across the populations of both X and Y cell types. In a few cases, LGN cells were recorded simultaneously with one of their retinal ganglion cell (RGC) inputs (S-potentials). In every case, the RGCs exhibited similar contrast-dependent effects in the space and spatial-frequency domains. We propose that this contrast dependency in the retinal ganglion cells results directly from a reduction in the size of the center mechanism due to an increase in contrast. We also propose that these properties first arise in the retina and are transmitted passively through the LGN to visual cortex.

High-order statistics of neural responses allow one to gain insight into neural function that may not be evident from firing rate alone. In this study, we compared the precision, reliability, and information content of spike trains from X- and Y-cells in the lateral geniculate nucleus (LGN) and layer IV simple cells of area 17 in the cat. To a stochastic, contrast-modulated Gabor patch, layer IV simple cells responded as precisely as their primary inputs, LGN X-cells, but less reliably. LGN Y-cells were more precise and reliable than LGN X-cells. Also, within each LGN cell type, 1) responses to the same stimulus were nearly identical if they shared the same center sign and 2) responses of neurons with the same center sign were nearly identical to the responses of neurons of opposite center sign if the stimulus' contrasts were inverted. These results suggest simple cells receive highly precise and synchronous LGN input, resulting in precise responses. Nonetheless, the response precision of simple cells was greater than expected. Finally, information-theoretic calculations of our cell responses revealed that 1) LGN X-cells encoded information at half the rate of LGN Y-cells but 2.5 times the rate of layer IV simple cells; 2) LGN cells encoded information in their responses using temporal patterns, whereas simple cells did not; and 3) simple cells used more of their information capacity than LGN X-cells. We propose mechanisms that simple cells might use to ensure high precision.