There’s No “The” in “Neural Code”

homer

One of the central, and most misunderstood, goals of the BRAIN Initiative is to understand how brains represent information. But, when people talk about cracking “the neural code,” what do they mean? It’s a reasonable metaphor, since it’s clear that brain activity in people (and animals) somehow represents the outside world in some abstract and non-trivial way. But there is really no single neural code. Not for different animals, and not even for different neurons within a single nervous system.

To really understand how different neural codes can be, we have to take a step back and look at how neurons represent their inputs, starting with one of the simplest of codes. Imagine you’ve got that glowing radioactive ingot that Homer Simpson fumbles around with. It’s in a lead-lined room on a table and you stand with your Geiger counter several feet away. What do you hear? Let’s say you are far enough away that you don’t hear anything, though you imagine if you waited around long enough in that position a stray particle might hit the collector and you would hear a single pop. So you move the wand closer and the sensor’s speaker starts to come to life, like the beginning of a hail storm on a tin roof. At some point there is a steady, though not regular, chatter that seems to max out as you touch the wand to the ingot. If you measured the number of pops-per-second from the Geiger counter, and plotted it against the distance of the wand from the ingot, it would probably look something like this:

sigmoid3

Now let’s say Lenny is in the next room (no windows) listening to your Geiger counter output. It’s his job to figure out how far away the rod is from the ingot at any given moment just from listening to the popping sounds on the speaker. You can imagine that if the radioactivity of the ingot is pretty constant, and with a little training, Lenny should be able to figure this out after a while. That is to say, given a certain rate of popping, Lenny can guess the distance reasonably accurately. So the pop-rate of the counter’s speaker is a code for the distance of the wand from the ingot. So the counter is transmitting information about an attribute of the world (the distance of the wand from the radioactive source). In this case, the information is contained only in the pop-rate, and not in the individual timing of pops (which are random), so that implies that Lenny has to listen to the speaker for a while to get an estimate of the rate (the presence or absence of the pop in a small time window doesn’t tell him much).

What this thought experiment describes is essentially one of the simplest and most common of neural codes, especially in sensory and motor systems. Imagine instead of a Geiger counter, you are listening to the activity of a neuron embedded in the skin that measures pressure. Like the Geiger counter, the information from most neurons is conveyed by discrete all-or-nothing events called action potentials (or spikes), so in this case you’d hear a pop pop pop on your audio monitor and that would tell you how much pressure was being put on the skin around the cell. With the proper experimentation, you’d be able to make a graph relating spike rate (say, in spikes per second) to pressure (maybe in pounds per square inch), and then you could estimate one from observing the other. That’s a neural code. This particular system is called a rate code, for obvious reasons, and because it’s so common in sensory systems and also for certain theoretical reasons, it’s essentially the default model of neural coding in many cases. Importantly, while it is easiest to grasp in terms of sensory coding, rate codes can also be used to describe the output of the nervous system, where motor neurons drive muscles in a process that converts spike rate into muscle contraction.

While rate codes are likely fundamental to most nervous systems, at least as a default hypothesis. When systems neuroscientists or BRAIN Initiative scientists suggest using techniques like calcium imaging, they are at least tentatively endorsing the centrality of rate codes. Because calcium imaging relies on relatively slow ion dynamics, it provides a reasonable readout for spike rate as a measure of neural activity, but it cannot resolve action potential timing in fine detail. Still, there are many neural subsystems in many different animals that appear to rely on more precise spike timing to relay information, and understanding these requires different techniques. I’ll describe some of these alternative coding strategies in future posts.

Photo Credit: The Simpsons opening sequence, under fair use guidelines.

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~ by nucamb on April 22, 2013.

9 Responses to “There’s No “The” in “Neural Code””

  1. Nice post! One could argue that the sensitivity of various Ca++ indicators has been getting faster, and in some systems can be used to detect very precisely the timing of individual spikes. Also, voltage imaging techniques have been improving, so detecting subthreshold events will also improve.

    • Yes, it’s certainly possible for those indicators (or other similar techniques) to advance to finer temporal resolutions, and everyone would be very happy if that came to pass. I simply wanted to point out how a certain technique embodied an assumption about the important time scale of neural coding.

      • the newest VSD from the Tsien group is quite nice… see this paper with fig. from my labmate there. I was sitting in the room when we first tested it and got single-spikes and subthreshold PSPs. very cool. No one’s talking much about it since it’s new and not yet genetically targetable, but developing this sort of thing is hopefully what BRAINI is about in the short term:

        http://www.pnas.org/content/109/6/2114.full

        (another figure here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403542/ )

      • Nice. That looks like a great advance in addressing some of the signal/noise issues with the old VSDs (for other readers, that stands for voltage-sensitive dyes). As they point out in the paper, they still need some kind of genetic targeting to keep from labeling everything (as the old dyes do). That is one of the nice things about the Ca dyes. They tend to show cell bodies well without washing out too much from non-specific fluorescence of the neuropil.

  2. Nice post.

  3. I can’t imagine them only focussing on measuring calcium signals. The idea is to use nanoparticles to respond to changes in the physiology. That doesn’t necessarily have to be clacium ions – calcium imaging works well for fluorescence imaging, but that is hardly an option when the goal is to image whole, living human brains. It could as well be potassium or sodium ions or voltage in itself… or neurotransmitter release… or neuromodulator release. All of those would make sense in a different context. Much more sense than calcium imaging, actually. Voltage imaging is not used as often, because it involves toxic dyes. This could be very different with nanoparticles.

    • No they certainly had never proposed focusing only on Ca signals, but Ca imaging is the technology that produces the highest cell counts at present. Typically, calcium imaging has been used in systems neuroscience (as opposed to cellular neuroscience, for example) as a readout of, or proxy for, the underlying spike rate. It’s certainly at least theoretically possible that you could measure other ions, but if you believe that action potentials attributable to individual neurons are the currency of neural coding and computation, then measuring neurotransmitter/neuromodulator release would mean you have to trace the release back to the source (which seems inefficient as a strategy to me).

      While I think the goal of measuring large-scale cell-specific activity in human brains is great in the _very_ long run, none of the BRAINI technologies are likely to be useful (or ethically defensible) for that purpose any time in the near future. As a case in point, there’s no reason to assume a priori that nanoparticles/nanowires would be any less toxic that voltage-sensitive dyes. Perhaps as with the proposals to send volunteers on a one-way mission to Mars, you might have people who would volunteer to have more invasive/experimental methods used. At present, though, there is no institutional review board that would allow that (and for good reason, really).

  4. Great topic and post. Will be a tough one considering nobody has even cracked the simple caw of the crow. Sure it can take slightly different tone, loudness, duration, and timing, but what I would stress is its extreme dependence on context (ie environment, either the organism’s surroundings or the neuron’s surroundings) so therefore any description of a code would also have to be big enough to include substantial portions of the environment. In that case it is virtually the same to say that the code might as well be assumed to be written anew in any given situation. That would perhaps be an easier assumption that to try then to assume certain codes apply to certain regions and times. Rather than looking for, or remembering any codes, assume there is no code, and apply the caws or spikes to whatever is at hand in the environment in any way you can imagine. That way if a crow migrates to a new clan, his “good stuff” caw, is not their “bad stuff” caw

  5. […] Rate codes are among the simplest ways to interpret the activity of neurons as they represent information in brains. Essentially, the stronger the stimulus, the more active the neuron, meaning that it fires more action potentials in given period of time. But what does that mean exactly? Answering that question requires diving into some cellular biology. […]

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