Haim Sompolinsky has written an excellent book chapter on the scientific view of free will and choice, pulling in good ideas from physics and neuroscience along with contemporary philosophical commentary.
I think this chapter might be helpful for neuroscientists outside of the lab. Often a dinner table discussion has moved to the idea of “quantum consciousness” or “quantum free will”. Often, someone will mention Roger Penrose, who has become something of a poster boy for this idea that quantum
indeterminacy (eg. Heisenberg’s uncertainty principle) is one possible way that free will is really free. And then, people look around and say, “Well, you’re a neuroscientist. Do we have free will?” (And that’s when I take another big drink or bite while I figure out something semi-coherent to say.)
Sompolinsky does a nice job of evaluating such claims (in the end, he says we cannot rule out the possibility that the brain is an indeterministic system but it seems unlikely) and provides nice scientific insight. In his view, it is far more likely that the brain’s apparent randomness (eg. individual cell spike rasters vary across repeated presentations of the same stimulus) is more simply explained by thermal noise (think of varying channel gating properties) and chaotic brain dynamics. (Recall, a chaotic system is still deterministic; it simply exhibits aperiodic behavior due to exquisite sensitivity to initial conditions. It is difficult to predict the long-term behavior of chaotic systems. The more we know the initial conditions in detail, the better our prediction.) On the other hand, he argues that the relevant length and time scales for neurons (micrometers and milliseconds) are far larger by many orders of magnitude than those of quantum noise. Chaos might amplify such quantum events, but this is far from being the simplest, most parsimonious explanation. Given the current level of neuroscience understanding, this is almost idle speculation. Regardless of the (in)determinacy of the world, Sompolinsky effectively argues against any non-physical, purely mental (ie. dualistic) agent of causation.
Thus, in sum, the world and our brains might not be determined but, even given that, there’s no reason to believe we have any causative ability to change things in the sense of traditional free will. These observations seem right on the mark to me. I hope they bring some insight for others. Or at least a way to fend off the dinner-table-free-will-conversation barrage of questions.
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.
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) , 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) .
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.
It seems Markram is again back to getting some interesting results. Recently a new discovery from the Brain Mind Institute of the EPFL shows that the brain adapts to new experience by unleashing a burst of new neuronal connections, and only the fittest survive. The research further shows that this process of creation, testing, and reconfiguring of brain circuits takes place on a scale of just hours, suggesting that the brain is evolving considerably even during the course of a single day.
The paper can be found Here.
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. Continue reading
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.
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.
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
I’ve been thumbing through pubmed, online resources, and lab members’ collective consciences looking for a complete list of pharmacological agents acting on receptors (i.e. metabotropic glutamate receptors), phenomena (i.e. AMPA receptor desensitization), and any other players that can affect neurotransmission at the synapse. No such list seems to exist.
So, if you have some knowledge to contribute, please add to this list of agents and effects on a new wiki page. Warning: the current format is really simple (any improvements would be welcome), but it’s a first pass at a much needed electrophysiology resource.