Archive for the ‘At the scale of cells and synapses’ Category

Enabling Neural Engineering Ought To Be The Measure Of Neuroscience

Monday, April 9th, 2007

The field of neuroscience naturally focuses its inquiry into neurons. This approach to understanding the brain by studying its parts has been thought to have a greater potential than that of psychology to understand how the brain works, a comment made by no less than Daniel L. Schacter, chair of Harvard’s Department of Psychology, in his book, The Seven Sins of Memory.

However promising the field has been thus far, even the most accomplished neuroscientists will admit that we still do not understand how the brain really works. I would submit that the current reductionist nature of neuroscience has shed much light on the dynamics of how neurons work, but has to a far lesser degree shed light on how neurons process information. The difference between these two lines of inquiry is important for making progress in understanding how the brain works.
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More halorhodopsin

Thursday, April 5th, 2007

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.

Survival of the sickest

Saturday, March 10th, 2007

Saw this book on the Daily Show a few nights ago and it looked interesting: Survival of the Sickest by Sharon Moalem

book cover

The author mentioned a theory of schizophrenia as due to toxoplasma infected cats, who are themselves infected by rats carrying the disease. Apparently, when the rat is infected, the toxoplasma alters the behavior of the rat such that it doesn’t run away from a cat. So, the parasite ensures its survival.

Although I’m not a big fan of just-so evolutionary explanations in general, this book sounds like it might be a fun read.

Optical silencing Cl- channel

Friday, March 9th, 2007

Ed strikes again!
Two-Color, Bi-Directional Optical Voltage Control of Genetically-Targeted Neurons

Having found a powerful method for activating neurons with blue light in the protein Channelrhodopsin-2 (ChR2) [1], we sought to augment the toolbox by finding a single-component system capable of mediating light-elicited neuronal inhibition. We identified a powerful tool, the mammalian codon-optimized version of the light-driven chloride pump halorhodopsin, from the archaebacterium Natronobacterium pharaonis (here abbreviated Halo) [2].

So, How Do REAL Neuronal Networks Compute?

Tuesday, February 20th, 2007

What is the right level of biological realism to model neuronal systems in order to understand their computational properties? Some recent papers may help shed some light on the subject. Models of the computational properties of local networks of neurons are starting to come into their own. This year has already seen at least two articles published in experimentalist journals based on the same core of theoretical work.

To bring you up to speed, I need to remind you what is going on in the world of experimental neuroscience.

Experimentalists are now able to record the single-cell activities of a whole population of neurons simultaneously. From Briggman, Abarbanel, Kristan (2006):

By using multi-electrode arrays or optical imaging, investigators can now record from many individual neurons in various parts of nervous systems simultaneously while an animal performs sensory, motor or cognitive tasks. Given the large multidimensional datasets that are now routinely generated, it is often not obvious how to find meaningful results within the data.

This paper goes on to provide a nice overview on mathematical methods that researchers are using to grapple with the challenge of understanding the dynamics of the neural systems they are recording from. They make the case that conceptual progress needs to be made on the interpretation of the data these results yield. How can we understand what computations these neurons are collectively performing?

(Incidentally, this topic is being explored in a conference happening this week at the Los Alamos National Laboratory, which, according to one of the conference session chairs, is intended to help shape future directions for the lab. Hopefully there will be webcasts from this conference.)

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Postdoctoral positions at Janelia Farm

Monday, February 19th, 2007

Postdoctoral/research scientist positions are available in the inter-disciplinary group of Dmitri Chklovskii at the new Janelia Farm Research Campus of the Howard Hughes Medical Institute located in the suburbs of Washington, D.C. Candidates are expected to have a PhD in neuroscience, physics, computer science or electrical engineering. Most of the work is theoretical or computational and is done in collaboration with several experimental laboratories. Successful applicants will work on projects centered on neuronal circuits such as high-throughput reconstruction of wiring diagrams as well as combining structural and physiological data to infer circuit function. Salary will be commensurate with qualifications. For more information about research directions in the group please see: http://www.hhmi.org/research/groupleaders/chklovskii.html
Interested applicants should send their CV and a statement of research interests to mitya (at) janelia.hhmi.org, and arrange for three recommendation letters to be emailed to me.

Amputee Controls And Feels Bionic Arm as Her Own

Friday, February 2nd, 2007

(UPDATE 03-05-2007 - Upon closer inspection, it is clear that while the surgery has enabled the woman to have sensation in the nerves of her missing hand when the surface of her chest is touched, the arm she is fitted with at the time of publication did not relay sensory signals from the arm back to her chest. As soon as she is fitted with an arm that has the appropriate sensors, however, she will not have to undergo further surgery to have this kind of direct feedback. Thanks to astute readers for pointing this out.)

The Guardian reports on an article published today in the Lancet about a successful surgical procedure giving an amputee a bionic arm that both responds to motor commands from her remaining motor nerves to control it and provides sensory feedback to sensory nerves when it is touched. If there was any doubt left, the worlds of neural prosthetics and brain-machine interfaces have officially collided.

The Lancet article is accompanied by two movies of the woman using the arm that you should really check out.

Given the recent progress in the decoding of motor signals from the brain and older progress on sensory feedback from neural prosthetics, this was to be expected. Nonetheless, watching this woman use her arm brings the message home in a visceral way. The spooky thesis of MIT CSAIL’s Rodney Brooks that “we will become a merger between flesh and machines” is one step closer today.

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Do sodium channels behave independently?

Monday, January 29th, 2007

A controversial paper proposed that sodium channels are not statistically independent when they open and close. This may have implications for the speed of neural computation.

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Modeling Time in Computational Neuroscience

Friday, December 29th, 2006

Computational neuroscience is a field where many successful researchers have a strong physics background. So far, the physics approach has provided a strong foundation from which to understand the brain. Recently, however, the influence of a computer science perspective has become more prominent. How can we understand the different perspectives that these disciplines bring to the field? Can we observe the influence of physics methodologies on the modern study of the brain? And if so, what is the consequence of our understanding of the brain through the lens of physics versus the lens of computer science?

One consequence may be the way that computational neuroscience models time in the brain. The study of physics generally conceptualizes time as continuous. Time is something to be plotted on the x-axis of a graph where some other quantity of interest is plotted on the y-axis.

In computer science, on the other hand, real time is rarely conceptualized explicitly. Computer scientists do not plot quantities against time unless they are profiling software for performance purposes, and even then, time is more generally thought of as number of operations. Thinking about operations generally leads computer scientists to think about time as discrete events.

I posit that the distinction between continuous and discrete time creates a foundational difference between the physics approach and the computer science approach to understanding how the brain works. Due to the discrete time conceptualization, computer scientists are more comfortable explaining the function of brain systems in terms of chains of events with definite beginnings and definite ends. Physicists, on the other hand, are more comfortable explaining the brain in terms of dynamics, which do not require definite beginnings or definite ends. Computer scientists care more what the consequence of an event is in the brain, whereas physicists are more concerned with an concise account of the dynamics of what is occurring.

This divide is visible in the distinct modeling approaches of neurons that derive from these two disciplines. The canonical neuronal model contributed by the physics philosophy is the multi-compartmental conductance based (Hodgkin-Huxley like) model. This model is concerned with matching waveforms of current and voltage traces with those that are measured in real neurons. This model helps us to understand how changes of the properties of excitable membranes over time result in changes of neuronal behavior over time. The computational complexity of these models is thought to prevent more than a few hundred neurons modeled in this way from being analyzed concurrently.

Alternatively, the canonical neuronal model contributed by the computer science philosophy is the integrate-and-fire neuron. This model does away with modeling conductances explicitly as functions of time and simply performs a weighted sum of its inputs at each time step. Here a time step is a discrete event whose duration is a parameter of the model. The simplicity of this model allows large networks to be constructed, which are useful for modeling systems of many thousands of neurons.

The physics approach provides insight into the activity of single cells and small networks, whereas the computer science approach provides insight into the activity of large networks. Neither approach is optimal and neither approach provides all the tools that are necessary to truly understand the brain. As these two perspectives are better understood, the field of computational neuroscience can benefit from finding creative ways to merge these two conceptions of time into models that capture both small scale and large scale neuronal activity.

In conclusion, I have demonstrated that what begins as a division between discrete and continuous time amounts to a divide between a bottom-up and a top-down approach. Furthermore, I have shown that understanding the relative contributions of different sciences to computational neuroscience is important for understanding the paradigms that pervade the field.

OpenStim: The Open Noninvasive Brain Stimulator

Tuesday, September 19th, 2006

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