On optogenetics

Go Baxter!

Mark Baxter

I’ve kind of wanted for a while to write something about methodology in behavioral/cognitive neuroscience (I want to reclaim “cognitive neuroscience” from being code for human fMRI, but that’s another post). Optogenetic technology – using light-activated ion channels or other proteins to manipulate neural activity – has swept many areas of neuroscience in the last few years as it has become widely distributed and successfully implemented in many laboratories. 

There is no doubt that the ability to manipulate neural activity with extremely high temporal and spatial resolution is revolutionary and promises many advances in understanding neural information processing. However, I think we’re at a point in this technology where all the exuberance about it is leading to a certain amount of mindlessness in experimental design and interpretation.

I was really delighted by reaction norm’s post about optogenetics and the dangers of oversimplifying what happens when you start to modify neurophysiology…

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Pattern Separation: What’s The Problem?!

I can’t believe I am writing a blog. Well, one entry at least, we’ll see where it goes from here. Maybe I’ll write about my two Big Obsessions: Science and Music. We’ll see.

For now, over on twitter (@Timothy_Bussey) we’ve been having a nice conversation about “pattern separation”. As you may know this putative process/construct/computation is suddenly of great interest to neuroscientists in part because it has been associated with adult neurogenesis (which itself is the topic of what has become a bit of a research sub-industry). There is even a website devoted to pattern separation!


So what is pattern separation? I think the website provides as good a definition of it as any:

 “The process of reducing interference among similar inputs by using non-overlapping representations.“

The classic example of the kind of interference pattern separation reduces involves car parking. If I ask you about something you did 3 days ago, you can probably give me a good answer. But if you park your car in the same multi-story car park every day, and I ask you where you parked your car 3 days ago, it is exceedingly difficult. The memories of parking your car every day are so similar that they are difficult to discriminate, and become confused in memory. Pattern separation is process that helps to reduce this confusion – we’d be a lot more confused about all sorts of memories if we didn’t have it!

Seems straightforward enough. However in “the field” there seems to be considerable confusion about, amongst other things, how people “define” pattern separation, if indeed they do (see below), and how it is best studied experimentally.

I thought I’d write down my preliminary thoughts about this because actually — I don’t see any problem at all! From where I’m coming from, the study of pattern separation seems to me to be nothing new or out of the ordinary. So I am very surprised by the confusion. Let me try to explain.

I am a behavioural/cognitive neuroscientist; my degrees are in Psychology. In behavioural/cognitive neuroscience we have a basic paradigm for working. We postulate a putative process/construct/computation in the brain, e.g., working memory, attention, whatever. Then we devise tasks to try to capture that function, e.g., delayed response, target detection, whatever. We try to have parameters that we can manipulate, e.g., delay, duration of target. If, say, a prefrontal cortex (PFC) damage leads to, say, a delay-dependent impairment in our delayed response task, we take this as evidence that the PFC is involved in working memory.

The behavioural pattern separation experiments — e.g., lesion the dentate gyrus, test on a putative test of pattern separation — are more of the same. As pattern separation putatively results in reducing the confusability, increasing the discriminability, of events, the parameter we manipulate is discriminability of events. There is nothing new under the sun here.

So when, for example, Adam Santoro writes that people, including me (Clelland et al., 2009, Science), define pattern separation as

“the literal behavioral ability to discriminate related stimuli”

and proceeds to rail against such a ‘definition’, I have no idea what he is talking about!

To return to the examples above, people who do those kinds of experiments on, e.g., working memory or attention are not defining delayed response as working memory, or target detection as attention. Those are just tasks, and they are using those tasks as assays of those putative processes/constructs/computations. (Of course one can always argue whether or not these are the right tasks to tap the constructs of interest, but that is a completely different issue.)

Now, having said that, Santoro is right in that some do seem to offer “behavioural” or “psychological” definitions of pattern separation — e.g. Hunsaker & Kesner — but I don’t really get that. There is no need for some separate behavioural definition of pattern separation. There are just tasks that we use to try to tap that putative function. Is this just semantics? I don’t think so; I think it’s important because talking about “behavioural definitions” will just fuel people’s misconception that there is something fundamentally different needed when studying pattern separation. But there isn’t — you don’t need a behavioural definition of pattern separation any more than there is a behavioural definition of working memory or attention.

So, What’s the problem?!

There isn’t one.

Discuss … ?