No evidence for intracellular magnetite in putative vertebrate magnetoreceptors identified by magnetic screening.

The cellular basis of the magnetic sense remains an unsolved scientific mystery. One theory that aims to explain how animals detect the magnetic field is the magnetite hypothesis. It argues that intracellular crystals of the iron oxide magnetite (Fe3O4) are coupled to mechanosensitive channels that elicit neuronal activity in specialized sensory cells. Attempts to find these primary sensors have largely relied on the Prussian Blue stain that labels cells rich in ferric iron. This method has proved problematic as it has led investigators to conflate iron-rich macrophages with magnetoreceptors. An alternative approach developed by Eder et al. [Eder SH, et al. (2012) Proc Natl Acad Sci USA 109(30):12022-12027] is to identify candidate magnetoreceptive cells based on their magnetic moment. Here, we explore the utility of this method by undertaking a screen for magnetic cells in the pigeon. We report the identification of a small number of cells (1 in 476,000) with large magnetic moments (8-106 fAm(2)) from various tissues. The development of single-cell correlative light and electron microscopy (CLEM) coupled with electron energy loss spectroscopy (EELS) and energy-filtered transmission electron microscopy (EFTEM) permitted subcellular analysis of magnetic cells. This revealed the presence of extracellular structures composed of iron, titanium, and chromium accounting for the magnetic properties of these cells. Application of single-cell CLEM to magnetic cells from the trout failed to identify any intracellular structures consistent with biogenically derived magnetite. Our work illustrates the need for new methods to test the magnetite hypothesis of magnetosensation.

Dopamine signals encode internally determined subjective value regardless of externally indicated reward attributes.

The dopamine reward prediction error signal is known to be subjective but has so far only been related to explicit external stimuli and rewards. However, personal choices are based on private internal values of the rewards at stake. Without indications of an agent's private internal value, we do not know whether dopamine neurons, or any reward neurons, encode the internal value. The well-established Becker-DeGroot-Marschak (BDM) auction-like mechanism allows participants to place bids for freely stating their private internal value for a good. BDM bids are known to reflect the agent's true internal valuation, as inaccurate bidding results in suboptimal reward ('incentive compatibility'). In our experiment rhesus monkeys placed BDM bids for juice rewards without specific external constraints. Their bids for physically identical rewards varied trial by trial and increased overall for larger rewards. Responses of midbrain dopamine neurons followed the trial-by-trial variation of bids despite constant, explicitly predicted reward amounts; correspondingly, the dopamine responses were similar when the animal placed similar bids for different reward amounts. Support Vector Regression demonstrated accurate prediction of the animal's bids by as few as twenty dopamine neurons, demonstrating the validity of the dopamine code for internal reward value. Thus, dopamine responses reflect the instantaneous internal subjective reward value rather than the value imposed by external stimuli.