Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex
Authors: Joshua P Taliaferro
Julia Cox
Yupu Liang
Ellia M Miller
Nathan F Parker
Jonathan W Pillow
Michelle Park
Malavika Murugan
Ilana B Witten
Hee Jae Jang
Hong Hur
Alexander R Nectow
Varun Bhave
Journal: Cell (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: calcium imaging; medial prefrontal cortex; nucleus accumbens; optogenetics; social behavior.
Affiliations: Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA., Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA., CCTS Bioinformatics Program, The Rockefeller University, New York, NY 10065, USA., Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA; Center for Statistics and Machine Learning, Princeton University, Princeton, NJ 08544, USA., Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA. Electronic address: .

Abstract:  Social behaviors are crucial to all mammals. Although the prelimbic cortex (PL, part of medial prefrontal cortex) has been implicated in social behavior, it is not clear which neurons are relevant or how they contribute. We found that PL contains anatomically and molecularly distinct subpopulations that target three downstream regions that have been implicated in social behavior: the nucleus accumbens (NAc), amygdala, and ventral tegmental area. Activation of NAc-projecting PL neurons (PL-NAc), but not the other subpopulations, decreased the preference for a social target. To determine what information PL-NAc neurons convey, we selectively recorded from them and found that individual neurons were active during social investigation, but only in specific spatial locations. Spatially specific manipulation of these neurons bidirectionally regulated the formation of a social-spatial association. Thus, the unexpected combination of social and spatial information within the PL-NAc may contribute to social behavior by supporting social-spatial learning. 

Retracted: No

PubPeer comments:
 Methods from this paper were used in the more recent Cameron et al (2019). [There] , I commented that Murugan et al s method for classifying putatively  spatially-selective neurons consists of simple correlation-fishing capable of  validating any assumption, including that some people are psychic. I ve copy-pasted those comments below.  A claim is made about the nature of neural function. The claim is that the activity of a particular neuron u2013 it s firing rate - represents a particular state of affairs in the physical world. That is, that via the photons reflected or emitted from objects entering the eyes, stimulating photoreceptors, etc., this external state of affairs is converted into the firing rate of a particular neuron, and this firing rate is then (somehow) interpreted by other parts of the brain as representing that (far more complex) state of affairs. For this putative neuron s firing rate to signify something in particular, reliably, it must somehow have a label an identifying feature. How is its identity signalled? By its location, its connections? In this case, they must be fixed. But the brain is plastic. And if the neuron is pre-labelled, does that mean it is just hanging out, on stand-by until its special external state of affairs arises? And how are new labels, representing new patterns of stimulation formed? Any time we start to scratch the surface of the neuron-as-detector notion, we open a Pandora s box of problems u2013 problems that reveal the concept as lacking in face-validity, as Teller observed way back in 1984. But it s the only game in town. The method used to investigate these hypothetical neurons functions is entirely immune to the truth or falsity of the underlying assumptions. It is akin to assuming some people have psychic powers, then asking a bunch of people to guess what the next roll of a die will be, or the next two rolls, etc; then declaring those who got it right to be psychic. It doesn t matter whether or not people really are psychic, you ll still get results. Some people u2013 and some neurons - will always beat the odds, by chance, their statements or activities coinciding with the relevant external events. What did the authors do to identify detector-neurons of the type assumed to exist u2013 neurons exhibiting u201cspatial selectivityu201d? They u201cused a Bayesian approach based on a Gaussian process (GP) regression model (Park et al., 2014) adapted for calcium fluorescence imaging data. This model provides a principled statistical framework for quantifying the relationship between spatial position and neural activity and has been described in detail elsewhere (Murugan et al., 2017).u201d So we have to go to Muragan et al (2017) to really learn what s what. A key passage in the methods: u201cTo assess the significance of each neuronu2019s spatial selectivity in the linear 3-chamber assay (Figures 4Du20134G, 5B, and 5C), a cross-validation method (based on leaving out 10% of the data) was used to compare the predicted fluorescence (based solely on the spatial field) with the actual fluorescence. Neurons were classified as having u2018significantu2019 responses when there was significant correlation between the predicted and actual fluorescence (p 0.05).u201d Thus, the existence of u201cspatial selectivityu201d is assumed, and those neurons whose activity (by an ad hoc criterion) happens to coincide with some description of external conditions are u201cclassifiedu201d as having the presumed property. Don t let the reference to u201ccross-validationu201d fool you; failure (of assumptions) is not an option here. Within the 10% of the held out data, whatever proportion of neurons which (post hoc) happened to match u201cpredictionu201d were classified as spatially-selective, and at the permissive standard of p .05. To extend my previous analogy, this seems analogous to taking a bunch of people, assessing their psychic powers as before, while leaving a few of their guesses results to one side. Then, of the people originally meeting the psychic standard (the  prediction is that they are, indeed, psychic), those whose original performances correlate with those held-out data (at a permissive standard of p .05) are classified as psychic. (Even in the context of proper experiments, p .05 has long been considered too permissive, resulting in many u201cfalse positives.u201d In this post hoc context, even a stricter standard would not validate the inferences; in this case, more (false) positives are a feature, not a bug). Would you consider such a procedure evidence that those individuals are psychic? And of course, we have the u201cprincipledu201d Bayesian exercise in post hoc data-fitting. It s a case of protesting too much u2013 there s nothing principled about post hoc data-fitting, Bayesian or otherwise u2013 it never replicates. The analysis is, as is the Bayesian way, built on numerous completely arbitrary assumptions: u201cWe assume neural activity in each time bin given the animalu2019s location follows a Gaussian distribution...u201d This is real bootstrapping - making major assumptions about the complex system you re supposed to be investigating, as a foundation for the conclusions of your investigation... u201cWe set the Gaussian process hyperparameters u03c1 and u03b4 and Gaussian noise variance u03c32 by maximizing marginal likelihood, the conditional probability of the data...u201d (The idea that neurons are u201cnoisyu201d is part of the detector scheme). u201cwe used the maximum a posteriori (MAP) estimate to determine the field for each neuron using standard formulas for the posterior under Gaussian prior and likelihood...u201d Is there any rationale for these choices, are they testable? (No). , 
 The analogy that I make in the comment above is a simple one. That means it should be easy to counter if its wrong. If any of the authors would like to challenge it, I d be happy to have that conversation. ,