Noradrenaline causes a spread of association in the hippocampal cognitive map

Abstract

The mammalian brain stores relationships between items and events in the world as cognitive maps in the hippocampal system. However, the neural mechanisms that control cognitive map formation remain unclear. Here, using a double-blind study design with a pharmacological intervention in humans, we show that the neuromodulator noradrenaline elicits a significant spread of association across the hippocampal cognitive map. This neural spread of association predicts overgeneralisation errors measured in behaviour, and is predicted by physiological markers for noradrenergic arousal, namely an increase in the pupil dilation response and reduced cortical GABAergic tone. Thus, noradrenaline sets the width of the smoothing kernel for plasticity across the cognitive map. Elevated noradrenaline can allow disparate memories to become linked, introducing potential for distortions in the cognitive map that deviate from direct experience. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=137 HEIGHT=200 SRC="FIGDIR/small/610602v3_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@85d4ceorg.highwire.dtl.DTLVardef@564073org.highwire.dtl.DTLVardef@a16111org.highwire.dtl.DTLVardef@ebe1fc_HPS_FORMAT_FIGEXP M_FIG C_FIG