A long-term in vitro silicon-based microelectrode-neuron connection

A novel method for long-term recording and simulation applicable to cultured neurons has been developed. Silicon-based microelectrodes have been fabricated using integrated-circuit technology and micromachining. The chronic connection is made by positioning the tip of the `diving-board electrode' into contact with the top of the cell body. The electrode support structure is then glued to the bottom of the culture dish. Two-way electrical connections to Helisoma B19 neurons have been maintained for up to four days. This capability makes it possible to conduct experiments that are not practical using conventional techniques

Conventional Synapses for Unconventional Cells

Powerful synapses between climbing fibers (CF) and Purkinje cells are crucial to cerebellar motor learning. In this issue of Neuron, Lin and colleagues provide compelling evidence for the existence of direct synaptic contacts between CFs and NG2-expressing glia cells, adding to the intrigue of neuro-glial interactions

Electrical activity increases growth cone calcium but fails to inhibit neurite outgrowth from rat sympathetic neurons

Previous studies have shown that the growth of axons from both mouse dorsal root ganglion neurons and Helisoma neurons is arrested when the cells are electrically stimulated (Cohan and Kater, 1986; Fields et al., 1990a). Furthermore, in the case of Helisoma neurons, this arrest has been attributed to a rise in the calcium concentration in the growth cones (Cohan et al., 1987). To test the generality of these results, we examined the response of cultured rat superior cervical ganglion (SCG) neurons to electrical stimulation and changes in cytoplasmic calcium. Suprathreshold electrical stimulation of SCG neurons at 10 Hz by extracellular patch electrodes for periods of up to 1 hr had no measurable effect on their rate of growth. In agreement with previous studies, electrical stimulation was accompanied by a rise in the internal calcium concentration: when measured by the fluorescence of fura-2, growth cone calcium levels rose from about 100 nM to greater than 500 nM and then settled to a plateau value of about 350 nM. Despite this increase, however, growth of SCG neurons' processes continued. Our results show that electrical activity is not a universal signal for neurons to stop growing and that a rise in internal calcium does not always arrest the migration of growth cones

Dynamics of Fast and Slow Inhibition from Cerebellar Golgi Cells Allow Flexible Control of Synaptic Integration

SummaryThroughout the brain, multiple interneuron types influence distinct aspects of synaptic processing. Interneuron diversity can thereby promote differential firing from neurons receiving common excitation. In contrast, Golgi cells are the sole interneurons regulating granule cell spiking evoked by mossy fibers, thereby gating inputs to the cerebellar cortex. Here, we examine how this single interneuron class modifies activity in its targets. We find that GABAA-mediated transmission at unitary Golgi cell → granule cell synapses consists of varying contributions of fast synaptic currents and sustained inhibition. Fast IPSCs depress and slow IPSCs gradually build during high-frequency Golgi cell activity. Consequently, fast and slow inhibition differentially influence granule cell spike timing during persistent mossy fiber input. Furthermore, slow inhibition reduces the gain of the mossy fiber → granule cell input-output curve, while fast inhibition increases the threshold. Thus, a lack of interneuron diversity need not prevent flexible inhibitory control of synaptic processing

Preserving professional credibility: grounded theory study of medical trainees’ requests for clinical support

Objective To develop a conceptual framework of the influences on medical trainees’ decisions regarding requests for clinical support from a supervisor

Endocannabinoids control the induction of cerebellar LTD.

Summary The long-term depression (LTD) of parallel fiber (PF) synapses onto Purkinje cells plays a central role in motor learning. Endocannabinoid release and LTD induction both depend upon activation of the metabotropic glutamate receptor mGluR1, require postsynaptic calcium increases, are synapse specific, and have a similar dependence on the associative activation of PF and climbing fiber synapses. These similarities suggest that endocannabinoid release could account for many features of cerebellar LTD. Here we show that LTD induction is blocked by a cannabinoid receptor (CB1R) antagonist, by inhibiting the synthesis of the endocannabinoid 2-arachidonyl glycerol (2-AG), and is absent in mice lacking the CB1R. Although CB1Rs are prominently expressed presynaptically at PF synapses, LTD is expressed postsynaptically. In contrast, a previously described transient form of inhibition mediated by endocannabinoids is expressed presynaptically. This indicates that Purkinje cells release 2-AG that activates CB1Rs to both transiently inhibit release and induce a postsynaptic form of LTD

Servo design and analysis for the Thirty Meter Telescope primary mirror actuators

The Thirty Meter Telescope has 492 primary mirror segments, each incorporated into a Primary Segment Assembly (PSA), each of which in turn has three actuators that control piston, tip, and tilt, for a total of 1476 actuators. Each actuator has a servo loop that controls small motions (nanometers) and large motions (millimeters). Candidate actuators were designed and tested that fall into the categories of "hard" and "soft," depending on the offload spring stiffness relative to the PSA structural stiffness. Dynamics models for each type of actuator are presented, which respectively use piezo-electric transducers and voice coils. Servo design and analysis are presented that include assessments of stability, performance, robustness, and control structure interaction. The analysis is presented for a single PSA on a rigid base, and then using Zernike approximations the analysis is repeated for 492 mirror segments on a flexible mirror cell. Servo requirements include low-frequency stiffness, needed for wind rejection; reduced control structure interaction, specified by a bound on the sensitivity function; and mid-frequency damping, needed to reduce vibration transmission. The last of these requirements, vibration reduction, was found to be an important distinguishing characteristic for actuator selection. Hard actuators have little inherent damping, which is improved using PZT shunt circuits and force feedback, but still these improvements were found to result in less damping than is provided by the soft actuator. Results of the servo analysis were used for an actuator down-select study

Submillimeter-wave antennas on thin membranes

Submillimeter-wave antennas with bismuth microbolometer detectors have been fabricated on 1-μm thick silicon-oxynitride membranes. This approach results in better patterns than previous lens-coupled integrated circuit antennas, and eliminates the dielectric loss associated with the substrate lens. Measurements on a wideband log-periodic antenna at 700 GHz, 380 GHz and 167 GHz, and on a 700 GHz log-periodic imaging array, show no sidelobee and a 3-dB beamwidth between 40° and 50°. Also, the effective area can be increased by 5 dB by the use of a back-shorting mirror. Possible application areas are superconducting tunnel junction receivers for radio astronomy and imaging arrays for plasma diagnostics

How to write an original article for the Journal of Orthopaedics and Traumatology

The abstract is the precise summary of the article, not a preface. As Baue wrote in a popular editorial of the Archives of Surgery in 1979, “writing a good abstract is not abstract writing” [6]. The main data have to be represented, as they allow readers to understand contents clearly. Sentences like “The paper reports...” or “The authors describe...” have to be avoided as well as any generic statements

Protein kinase C is a calcium sensor for presynaptic short-term plasticity

In presynaptic boutons, calcium (Ca2+) triggers both neurotransmitter release and short-term synaptic plasticity. Whereas synaptotagmins are known to mediate vesicle fusion through binding of high local Ca2+ to their C2 domains, the proteins that sense smaller global Ca2+ increases to produce short-term plasticity have remained elusive. Here, we identify a Ca2+ sensor for post-tetanic potentiation (PTP), a form of plasticity thought to underlie short-term memory. We find that at the functionally mature calyx of Held synapse the Ca2+-dependent protein kinase C isoforms α and β are necessary for PTP, and the expression of PKCβ in PKCαβ double knockout mice rescues PTP. Disruption of Ca2+ binding to the PKCβ C2 domain specifically prevents PTP without impairing other PKCβ-dependent forms of synaptic enhancement. We conclude that different C2-domain-containing presynaptic proteins are engaged by different Ca2+ signals, and that Ca2+ increases evoked by tetanic stimulation are sensed by PKCβ to produce PTP. DOI: http://dx.doi.org/10.7554/eLife.03011.00