neurodudes

Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential : Nature

Very interesting work. Modulation of the somatic potential seems to influence the EPSP, as measured by paired patch recordings of two layer 5 cells in cortical slice. Somatic depolarization from resting potential to near threshold results in an increase in evoked EPSPs.

In synaptic physiology, we often make a point of distinguishing intrinsic changes (eg. membrane potential) from synaptic conductance changes. Now it looks like the line between those might be a bit blurry!

Here’s a N&V by Eve Marder too.

Cell : Astrocytes Put down the Broom and Pick up the Baton [N&V summary]

Some beautiful work [original article] by Oliet’s lab in a recent issue of Cell demonstrates the importance of glia in synaptic plasticity. The show a system where D-serine and not glycine controls the NMDA receptor in a coagonist role (or perhaps glutamate is really the coagonist…) and show how similar pairing protocols can have opposite effects (LTD vs. LTP) depending on D-serine modulation by astrocytes. Yet more hidden factors in plasticity are being revealed!

Here’s the key figure:

More details from the News & Views summary after the jump. (more…)

Synaptic tuning : Nature Reviews Neuroscience

For those interested in neuromodulators:

Treatment of striatal neurons with a D1 receptor agonist led to an increase in the dendritic staining intensity of NMDA receptor NR2B subunits. There was also an increase in the association of NR2B subunits with PSD-95 — a scaffold protein required for the assembly of NMDA receptors — and in the surface localization of NR2B-containing receptors.

Original article in J. Neurosci. from Dunah and colleagues. An excerpt from the original aricle of a neat application of FRET continues after the jump.
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A FRET-Based Calcium Biosensor with Fast Signal Kinetics and High Fluorescence Change — Mank et al. 90 (5): 1790 — Biophysical Journal

Relevant details (from the discussion):

Above we reported the generation of a FRET-based calcium biosensor employing TnC as calcium-binding moiety that is fast, is stable in imaging experiments, and shows a significantly enhanced fluorescence change. Its off-rate is significantly faster than those of previous double chromophore sensors and even outmatches the fastest single fluorophore sensors to date.

Although it is faster than what was previously available, it would be nice if the off-rate was even faster:

Its off-rate was extremely fast, optimally fitted with a double exponential with a dominating {tau} of 142 ms (A1 = 0.63) and a minor {tau} of 867 ms (A2 = 0.06) (Fig. 2 D). Mutation of the N-cap residue 131 of helix G within TnC from isoleucine to threonine (35Go) yielded an indicator of higher calcium affinity with a Kd of 1.7 µM (Fig. 2 B) and shifted the Hill slope to 1.1, although at reduced maximal fluorescence change of 270%. TN-XL expressed well in primary hippocampal neurons at 37°C. Fluorescence was evenly distributed, filling all neuronal processes, with no signs of aggregation. The nucleus was devoid of fluorescence. Repeated stimulations with high potassium followed by repeated washouts demonstrated stable baselines over long recording sessions and reproducible signals after stimulation. Moreover the signals induced by high potassium were more than doubled compared to TN-L15.

Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes — Rigoutsos et al. 103 (17): 6605 — Proceedings of the National Academy of Sciences

Not directly neuroscience-related but this is a pretty cool paper nonetheless. Basically, the authors use automated pattern recognition to pick out small strings in the “non-coding” regions of the human genome. They show that these pyknons are found at regular distances within coding regions and UTRs. Even more intriguing is that

approx. 40% of the known microRNAs are similar to 689 pyknons and that the pyknons subsume 56 of the 72 recently reported 3′ UTR motifs, lending further support to the possibility of a connection between the pyknons and RNAi/PTGS.

Both RNAi (RNA interference) and PTGS (post-transcriptional gene silencing) have recently been found to be major regulatory mechanisms for endogenous gene silencing and regulation. Here’s a link to a primer on PTGS and RNAi.

Two Coincidence Detectors for Spike Timing-Dependent Plasticity in Somatosensory Cortex — Bender et al. 26 (16): 4166 — Journal of Neuroscience

Dan Feldman’s group at UCSD has found that different “sides” of STDP (ie. LTP vs. LTD) at cortical synapses might be mediated through distinct signalling pathways. The major finding was that LTD was induced independent of NMDA receptors. Rather, LTD required mGluRs and VGCCs.

There are many questions here. The most interesting to think about is, Are we going to find different STDP rules all over the brain? And, if so, what will be the commond ground between them?

Here’s the abstract:

Many cortical synapses exhibit spike timing-dependent plasticity (STDP) in which the precise timing of presynaptic and postsynaptic spikes induces synaptic strengthening [long-term potentiation (LTP)] or weakening [long-term depression (LTD)]. Standard models posit a single, postsynaptic, NMDA receptor-based coincidence detector for LTP and LTD components of STDP. We show instead that STDP at layer 4 to layer 2/3 synapses in somatosensory (S1) cortex involves separate calcium sources and coincidence detection mechanisms for LTP and LTD. LTP showed classical NMDA receptor dependence. LTD was independent of postsynaptic NMDA receptors and instead required group I metabotropic glutamate receptors and calcium from voltage-sensitive channels and IP3 receptor-gated stores. Downstream of postsynaptic calcium, LTD required retrograde endocannabinoid signaling, leading to presynaptic LTD expression, and also required activation of apparently presynaptic NMDA receptors. These LTP and LTD mechanisms detected firing coincidence on ~25 and ~125 ms time scales, respectively, and combined to implement the overall STDP rule. These findings indicate that STDP is not a unitary process and suggest that endocannabinoid-dependent LTD may be relevant to cortical map plasticity.

From the Apr 20 issue of Neuron: Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons (or, for those who want just the N&V’s summary: Dendritic Enlightenment: Using Patterned Two-Photon Uncaging to Reveal the Secrets of the Brain’s Smallest Dendrites)

The technology is essentially high-speed two photon uncaging of glutamate, but the authors have used it here to create “realistic” patterns of dendritic input in an attempt to see just how dendritic arithmetic works. Although I haven’t read the paper closely, they claim to work out the spatiotemporal parameters underlying dendritic spike generation for pyramidal neurons.

A related methodology paper from a recent J. Neurophys. also uses fast acousto-optic deflectors and two-photon but for imaging purposes. It’s more descriptive about the setup and techniques for those interested in doing this type of work.

The lab of David McCormick at Yale has released a paper that shows neurons operating in both analog and digital modes simultaneously.

From an article about the finding:

“McCormick’s group demonstrated that the analog signal present in the cell body also propagates down the axon and influences synaptic transmission onto other neurons. As the voltage on the sending cell becomes more positive, the amplitude of the subsequent transmission to the receiving cell, mediated by an action potential, is enhanced. This means that the waveform generated in the receiving neuron is not just determined by the digital pattern of action potentials generated, but also by the analog waveform occurring in the sending neuron.”

McCormick is a big name in the field. Is it time to start creating a new field of artificial neural networks that has both analog and digital modes?

How would you cure blindness, if your phototransducing rods and cones had degenerated - as happens in syndromes that affect millions of people worldwide? A lot of investigators have tried to create very complicated electrical stimulators that drive patterned activity in the retina. You need a power source, a camera of sorts, a computational element, and an array of electrodes that can crank out precise, well-timed current pulses, for a long time. It’s a heroic piece of optical and electrical engineering.

But what if you just made other cells in the retina light-sensitive? Channelrhodopsin and other light-activated ion channels have opened up this new kind of endeavor.

Investigators at Wayne State University, the Pennsylvania College of Optometry, and Beijing University have now done this. They expressed Channelrhodopsin in retinal ganglion cells (RGCs) of mice with photoreceptor degeneration. Remarkably, for months afterwards, the RGCs were able to transmit visual information all the way to visual cortex. In mice without channelrhodopsin, these visual evoked responses were never seen. A very impressive piece of systems bioengineering.

Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration
Anding Bi, Jinjuan Cui, Yu-Ping Ma, Elena Olshevskaya, Mingliang Pu, Alexander M. Dizhoor, and Zhuo-Hua Pan

— Ed

How do crickets know when they are chirping?

These questions appear to be answered with the discovery of a motor interneuron in the cricket that is resposible for “corallary discharge” or forwarding neural signals from motor systems to sensory systems. By inhibiting auditory neurons during chirping, the animal can “counter the expected, self-generated sensory feedback”.

Over at the synapse blog, it is pointed out that the cerebellum may have this function in vertebrates.