Adaptive binning in the retina

The Circadian Clock in the Retina Controls Rod-Cone Coupling (Christophe Ribelayga, Yu Cao, and Stuart C. Mangel)

An amazing paper from Neuron demonstrating adaptive (circadian clock-governed) binning in the retina, based on dopamine modulation of gap junction (electrical) synapses between retinal photodetectors. During the day, abundant dopamine release weakens gap junctions coupling rods and cones together so that visual acuity is high. When light is scarce (at night), there is less dopamine and the electrical coupling between rods and cones is increased. This is analogous to on-chip binning in CCD (digital) cameras. Binning increases signal (in light-limited systems, eg. seeing at night) by increasing optical input area and by reducing single element noise (ie. noise at different photoreceptors should be independent) at the cost of resolution. So, the retina activates photoreceptor binning at night to boost low-light signals and deactivates it during the day to increase resolution. The dopamine comes from cells in the interplexiform layer, whose dopamine release is itself governed by melatonin projections.

Also, I never knew that gap junction strengths were directly modifiable. It looks like the D2 receptors are G-protein coupled to PKA, which acts on the gap junctions.

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Neuroengineering mosquito repellents

There has been a few articles recently in the NYT about the neural mechanisms used by mosquito repellents. What a wonderful idea: Do some ephys recordings to find which neurons are sensitive to DEET (the current standard for mosquito repellents, which I can attest both doesn’t work very well and eats holes in synthetic clothing) and then build targeted compounds for those receptors/neurons/pathways. I always like this type of simple and practical neuroengineering.

Right now, it appears that there’s a bit of controversy in the field. Earlier this year, in Science, a group from Rockefeller found that DEET masked sensitivity to human odors by interfering with a particular odorant receptor. This impressive result was recently question by entomologists from UC-Davis in a PNAS paper claiming that DEET acts directly on a particular olfactory receptor neuron and does not attenuate the response to the same human-emitted odorant, as found in the earlier paper. Although the results appear to be conflicting, the studies use different techniques and thus it is likely that DEET’s action might be more complex than either paper claims. Still, the idea of identifying a target for chemical intervention by looking at electrophysiological responses to DEET is smart.

In related work, earlier this year a group from Colorado State University, as described in this PNAS overview, “conducted a rigorous search of a library of N-acylpiperidines, using an artificial neural network to identify strong candidates, and then tested them in the laboratory on human volunteers.” They found a candidate molecule that has a ~4X longer repellency effect than DEET. Here’s a photo from the experiments (DEET vs. untreated hand)… ouch!

Lots of flies on the untreated hand!

Real-time STED to visualize vesicle dynamics

Video-Rate Far-Field Optical Nanoscopy Dissects Synaptic Vesicle Movement

Just the optical engineering alone here deserves mention: 28 frames per second at 62nm resolution (well below the diffraction limit of 260nm for light of the wavelength used)! STED (or stimulated emission depletion, developed in Stefan Hell’s group) is ideal for visualizing synaptic vesicles, whose small size (~50nm) has typically confined them to the domain of electron microscopists. The ability to get high-speed STED allowed the researchers to track individual vesicles and their path dynamics. They conclude that vesicle movement has both motor-driven and diffusive components (ie. a biased random walk). I’m sure with more time and more analysis there will be a lot of interesting applications for this kind of real-time vesicle tracking. Perhaps in the near future we will have single vesicle “minis” monitored at multiple sites through microscopy instead of just one or two sites electrophysiologically…

Here’s the resolution difference between STED and confocal for a single vesicle:
Sted vs. confocal vesicle picture

And, for those of you with ~$1.25M lying around, you can now purchase a STED setup directly from Leica!

competition: single-neuron prediction

Gerstner‘s group in Lausanne, Switzerland has announced a competition to predict the electrical behavior of individual neurons in two respects:

1) predict the timing of every spike that a neuron emits with a precision of 2ms.
2) predict the subthreshold membrane potential with a precision of 2mV for arbitrary input.

Details on the competition, including the dataset (released 16 March 2007), are here.

Note that the first prize winner receives:

– 4 nights of hotel in Lausanne at the Lake Geneva, June 23-27.
– Free participation in the Quantitative Neuron Modeling workshop June 25/26
– 35-minute-slot for talk as an Invited Speaker in the workshop.

get coding.

(posted by Dave Matthews)

More halorhodopsin

This week’s Nature has quite a few additional halorhodopsin articles for photochannel fans.

Halorhodopsin article from Deisseroth’s lab:
Multimodal fast optical interrogation of neural circuitry [News & Views]

Also, there is an intriguing article on both the general excitement in the neuroscience community with this new technology and a possible intellectual property dispute over it.

OpenStim: The Open Noninvasive Brain Stimulator

Transcranial magnetic stimulation (TMS) is a popular technology for stimulating human cortical neurons, due to its safety, noninvasiveness, and efficacy. A TMS device is just a little coil of wire, through which 10,000 Amps of current is cranked during a period of only a few hundred microseconds; the resultant rapidly-changing magnetic field induces eddy currents in the brain. Depending on the protocol used, TMS can drive/inhibit a region of cortex corresponding to roughly a cubic centimeter or two, and is being explored for the treatment of depression, the reduction of auditory hallucinations during schizophrenia, and the alleviation of tinnitus and migraines. Thousands of papers on medicine and psychology have been written using this tool.

Yet the device itself is expensive and rare — they can run from $20,000 to $50,000 or even more, despite the fact that they are, in essence, a coil, a switch, a bank of capacitors, and a power supply. Much of the art lies in making the devices safe and fail-proof. Is it possible to hack/engineer a system that is safe, fault-tolerant, efficacious, and inexpensive? And furthermore, can we facilitate a community that will devise such devices, and share information about protocols and approaches to brain hacking?

This past August at Foo Camp, a hackers’ conference in Northern California, a group of people got together and set out to do just that. We are designing a safe, noninvasive, modular, and “open source” brain stimulator that will open up the field of circuit modulation to a wider audience. Members of the group include therapists and mental health professionals, engineers, programmers, and others interested in either the development of such devices, or the sharing of information on this front. Key to the design is safety — we want to make sure that the devices we create are as safe as devices on the market. Also, all the information is released under the Creative Commons “Attribution and Sharealike” license. This is a new model for “open source” medical device development — which may move it beyond the domain of simply creating “cool toys,” and to creating real devices.

You can find out more information, or contribute to the project, or learn from the project, at
http://transcenmentalism.org/OpenStim/

Ed