28Learning to associate malaise with the intake of novel food is critical for survival. Since 29 food poisoning may take hours to affect, animals developed brain circuits to transform the 30 current novel taste experience into a taste memory trace (TMT) and bridge this time lag. Ample 31 studies showed that the basolateral amygdala (BLA), the nucleus basalis magnocellularis 32 (NBM) and the gustatory cortex (GC) are involved in TMT formation and taste-malaise 33 association. However, how dynamic activity across these brain regions during novel taste 34 experience promotes the formation of these memories is currently unknown. We used the 35 conditioned taste aversion (CTA) learning paradigm in combination with short-term 36 optogenetics and electrophysiological recording in rats to test the hypothesis that temporally 37 specific activation of BLA projection neurons is essential for TMT formation in the GC, and 38 consequently CTA. We found that late-epoch (LE, >800ms), but not the early epoch (EE, 700ms), BLA activation during novel taste experience is essential for normal CTA, for early 40 c-Fos expression in the GC (a marker of TMT formation) and for the subsequent changes in 41 GC ensemble palatability coding. Interestingly, BLA activity was not required for intact taste 42 identity or palatability perceptions. We further show that BLA-LE information is transmitted 43 to GC through the BLA→NBM pathway where it affects the formation of taste memories. 44 These results expose the dependence of long-term memory formation on specific temporal 45 windows during sensory responses and the distributed circuits supporting this dependence. 46 47 48 49 50 51 52 4 53 Significance 54Consumption of a novel taste may result in malaise and poses a threat to animals. Since 55 the effects of poisoning appear only hours after consumption, animals must store the novel 56 taste's information in memory until they associate it with its value (nutritious or poisonous).
57Here we elucidate the neuronal activity patterns and circuits that support the processing and 58 creation of novel-taste memories in rats. Our results show that specific patterns of temporal 59 activation in the basolateral amygdala transmitted across brain areas are important for 60 formation of taste memory and taste-malaise association. These findings may shed light on 61 long-term activity-to-memory transformation in other sensory modalities. 62 63 64 Neuronal dynamics 66 67A novel food poses a dilemma to animals: To eat or not to eat? On the one hand a 68 new food may be highly nutritious, but on the other hand it may be toxic and life 69 threatening (Rozin, 1976). To avoid the fatal consequences of poisoning, brain circuits 70 have evolved to quickly detect novel tastes, transform these tastes into novel-taste memory 71 trace (TMT)(Bermudez-Rattoni, 2014) to bridge the time-lag between consumption and 72 malaise, and form a taste-malaise association (termed conditioned taste aversion [CTA]) 73 (Garcia et al., 1955).
74Decades of research have identified ma...