Technique: Fiber Photometry Calcium Imaging

<<La solitude vivifie ; l’isolement tue.>>

Joseph Roux


Paper: Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation

Fiber photometry calcium imaging is a method that allows us to measure neural activity in a particular population of neurons by means of genetic and fluorescent recording techniques in freely moving mice. First, luminescent calcium indicators (e.g., GCaMP6m in this paper) are genetically expressed in a desired set of neurons. Next, an optic fiber is surgically placed above the population of neurons expressing the calcium indicator. Finally, the optical fiber works in a bidirectional way. That is, the system of optical fibers excites and records the activity of the calcium indicators thanks to a dichroic mirror and a photodetector. More specifically, the fiber excites the GCaMP6m with light at about 470nm and the recorded activity is compared to the baseline of around 410nm or 430nm of background excitation. Notice that such measurements are the overall activity of the entire set of neurons. In addition, fiber photometry is particularly attractive when we want to record the activity of freely moving mice (unlike other methods that require animals to be head-fixed for calcium recording). In general, this technique is useful when dissecting neural circuits because it allows scientists to implant multiple fibers and record the activity of a particular set of neurons when other populations of neurons are excited as well. The real-time recording ability of fiber photometry permits researchers to compare the activity of different neural populations and see what neurons are related to the orchestration of a particular behavior.

The figure below (figure 2 A, B) shows a schematic and real microscopic representation of how fiber photometry was set up in the freely moving mice in this experiment. The researchers in this paper were trying to study how social isolation affected the activity of dorsal raphe nucleus (DRN) dopamine (DA) neurons. In order to do this, they had two experimental groups. One group of mice was socially isolated while the other one was allowed to hang out with other mice. Of course, these mice were previously injected with adeno-associated viral vectors to express GCaMP6m in dopamine neurons of the DRN. Then the individual mice in the fiber photometry set up were presented to a young mouse. The fiber photometry recordings showed that isolated mice had a significantly greater fluorescent response to this new mouse (Figure 2 C). Furthermore, in order to avoid any possible confounds, the authors compared this neural activity to a control: a new object instead of a new mouse in the same experimental setup. Indeed, the response of isolated mice in fiber photometry was greater for the new mouse than for the new object. The authors concluded that, after experiencing social isolation, DA neurons in the DRN have a significant greater activity when exposed to a social stimulus. Of course, this is just a correlation because fiber photometry does not allow us to make conclusions about causation. Optogenetic manipulations would be necessary to corroborate causation.

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Matthews Gillian A, Nieh Edward H, Vander Weele Caitlin M, Halbert Sarah A, Pradhan Roma V, Yosafat Ariella S, Glober Gordon F, Izadmehr Ehsan M, Thomas Rain E, Lacy Gabrielle D, Wildes Craig P, Ungless Mark A, Tye Kay M Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell 164:617-631.