Graphical AbstractHighlights d NSM is an enteric serotonergic neuron that is activated by food ingestion d Two ASIC channels, DEL-7 and DEL-3, mediate feedinginduced NSM activation d Activation of NSM neurons drives slow locomotion while animals feed d Changes in NSM response dynamics alter foraging behavior dynamics A sensory mechanism for food sensing and feeding-associated behaviors is mediated by two ASIC ion channels. SUMMARYAnimals must respond to the ingestion of food by generating adaptive behaviors, but the role of gutbrain signaling in behavioral regulation is poorly understood. Here, we identify conserved ion channels in an enteric serotonergic neuron that mediate its responses to food ingestion and decipher how these responses drive changes in foraging behavior. We show that the C. elegans serotonergic neuron NSM acts as an enteric sensory neuron that acutely detects food ingestion. We identify the novel and conserved acid-sensing ion channels (ASICs) DEL-7 and DEL-3 as NSM-enriched channels required for feeding-dependent NSM activity, which in turn drives slow locomotion while animals feed. Point mutations that alter the DEL-7 channel change NSM dynamics and associated behavioral dynamics of the organism. This study provides causal links between food ingestion, molecular and physiological properties of an enteric serotonergic neuron, and adaptive feeding behaviors, yielding a new view of how enteric neurons control behavior. This paper SWF64 C. elegans: delThis paper SWF65 (Continued on next page) e1 Cell 176, 85-97.e1-e6, January 10, 2019 Continued REAGENT or RESOURCE SOURCE IDENTIFIER C. elegans: del

To sense the outside world, some neurons protrude across epithelia, the cellular barriers that line every surface of our bodies. To study the morphogenesis of such neurons, we examined the C. elegans amphid, in which dendrites protrude through a glial channel at the nose. During development, amphid dendrites extend by attaching to the nose via DYF-7, a type of protein typically found in epithelial apical ECM. Here, we show that amphid neurons and glia exhibit epithelial properties, including tight junctions and apical-basal polarity, and develop in a manner resembling other epithelia. We find that DYF-7 is a fibril-forming apical ECM component that promotes formation of the tube-shaped glial channel, reminiscent of roles for apical ECM in other narrow epithelial tubes. We also identify a requirement for FRM-2, a homolog of EPBL15/moe/Yurt that promotes epithelial integrity in other systems. Finally, we show that other environmentally exposed neurons share a requirement for DYF-7. Together, our results suggest that these neurons and glia can be viewed as part of an epithelium continuous with the skin, and are shaped by mechanisms shared with other epithelia.

The basolateral complex of the amygdala (BLA) is critical for the acquisition and expression of Pavlovian fear conditioning in rats. Nonetheless, rats with neurotoxic BLA lesions can acquire conditional fear after overtraining (75 trials). The capacity of rats with BLA lesions to acquire fear memory may be mediated by the central nucleus of the amygdala (CEA). To examine this issue, we examined the influence of neurotoxic CEA lesions or reversible inactivation of the CEA on the acquisition and expression of conditional freezing after overtraining in rats. Rats with pretraining CEA lesions (whether alone or in combination with BLA lesions) did not acquire conditional freezing to either the conditioning context or an auditory conditional stimulus after extensive overtraining. Similarly, post-training lesions of the CEA or BLA prevented the expression of overtrained fear. Lastly, muscimol infusions into the CEA prevented both the acquisition and the expression of overtrained fear, demonstrating that the effects of CEA lesions are not likely due to the destruction of en passant axons. These results suggest that the CEA is essential for conditional freezing after Pavlovian fear conditioning. Moreover, overtraining may engage a compensatory fear conditioning circuit involving the CEA in animals with damage to the BLA.Pavlovian fear conditioning is an important model for studying the neural mechanisms contributing to emotional learning and memory (Davis 1992;LeDoux 2000;Maren 2001Maren , 2005a. In this paradigm, a conditioned stimulus (CS), such as a tone, is presented with an aversive unconditional stimulus (US), such as a footshock. The pairing of the CS and the US comes to elicit conditioned fear responses (CRs), including increased heart rate, blood pressure, acoustic startle, and somatomotor immobility (i.e., freezing). It is now well established that the amygdala is critical for this form of learning (Fendt and Fanselow 1999 In contrast, the medial division of the CEA (CEm) has been posited to be the primary output structure of the amygdala. The CEA receives information from the LA via the intercalated nuclei, and it also receives direct projections from the BL and thalamus. The CEm, in turn, projects to brain areas involved in the production of the CR, including the periaqueductal gray and the lateral hypothalamus, which mediate freezing and cardiovascular response, respectively (LeDoux et al. 1988). However, recent studies suggest that the CEA may also have a role in the acquisition of conditional fear (Goosens and Maren 2003;Maren 2005a;Wilensky et al. 2006), and it is anatomically positioned to serve this role (Pare et al. 2004). These findings lend support to two competing models of information processing within the amygdala during learning. In the serial model, information about the CS and US enter and are associated within the BLA, and this information is then transmitted to the CEA for the expression of fear. Alternatively, the parallel model proposes that the BLA and CEA both perform associative function...

Remodelling neuronal connections by synaptic activity requires membrane trafficking. We present evidence for a signalling pathway by which synaptic activity and its consequent Ca2+ influx activate the small GTPase Ral and thereby recruit exocyst proteins to postsynaptic zones. In accord with the ability of the exocyst to direct delivery of post‐Golgi vesicles, constitutively active Ral expressed in Drosophila muscle causes the exocyst to be concentrated in the region surrounding synaptic boutons and consequently enlarges the membrane folds of the postsynaptic plasma membrane (the subsynaptic reticulum, SSR). SSR growth requires Ral and the exocyst component Sec5 and Ral‐induced enlargement of these membrane folds does not occur in sec5−/− muscles. Chronic changes in synaptic activity influence the plastic growth of this membrane in a manner consistent with activity‐dependent activation of Ral. Thus, Ral regulation of the exocyst represents a control point for postsynaptic plasticity. This pathway may also function in mammals as expression of activated RalA in hippocampal neurons increases dendritic spine density in an exocyst‐dependent manner and increases Sec5 in spines.