Does knowing where neurons are headed tell you what they do?

April 4, 2015

In our lab meeting this week, we read a paper by Nuo Li, Karel Svoboda. These guys have been probing the function of a secondary motor area, ALM, for a while now, and have previously implicated it as playing a role in sensory guided movements, especially those following a delay. Here, they delved in deeper, asking how neurons within ALM drive movements. The work started with a puzzling observation: when you record neurons within ALM, they are a mixed bag in terms of what makes them respond: some respond in advance of movements to the contralateral side and others respond in advance of movements to the ipsilateral side. Here’s the weird part: when you disrupt this area, contralateral movements are particularly affected. This new result tackles that disconnect.

What these guys found is that mixednature14178-f4 bag of neurons that is apparent during recording is actually comprised of two populations, each with its own response properties. Some neurons (the green ones in the figure) project to brainstem nuclei, while others (the purple ones) project to ALM on the other side. Importantly, the former group is distinct: those neurons tend to respond preferentially in advance of contralateral movements, and when you stimulate them specifically, a contralateral bias is observed.

This is a big deal for a few reasons. First, the experiments leveraged really cool tools that made it possible to selectively activate a projection-defined population of neurons. Second, it suggests that the heterogeneity of responses that electrophysiologists observe might be partly explained by the projection target of each recorded neuron. A population might only appear to be heterogeneous because traditional electrophysiology experiments don’t tell the experimenter anything about where neurons are projecting. However…  I don’t know whether this will always be the case. When I was a graduate student with Steve Lisberger, I used antidromic stimulation, a classic technique also used in the current paper, to identify extrastriate cortex neurons projecting to the frontal cortex. In my (admittedly small) population, the response properties of projection neurons didn’t differ in any obvious way from the general population. So it may be that projection target can predict some properties of neurons in some areas, but that even a group of neurons with a shared target can nonetheless be very heterogeneous.

A final thought: while discussing this paper in lab meeting, it was fun telling the students and postdocs in my lab about my own experiences identifying projection neurons and using the collision test to demonstrate the direction of the connectivity. It turns out that, back in the day, I actually made a movie of this! The lab claims it was clarifying, so I include it here for educational and amusement purposes.


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Fairhall lab

Computational neuroscience at the University of Washington

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Neural Coding and Computation Lab @ Princeton University

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Perceptual decision-making at Cold Spring Harbor

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