Ueoka, Y. | Search bioRxiv

bioRxiv2023

Revisiting the role of cAMP in Drosophila aversive olfactory memory formation

In the olfactory aversive conditioning of Drosophila melanogaster, an odor, the conditioned stimulus (CS), is associated with electric shock, the unconditioned stimulus (US). The Rutabaga adenylyl cyclase in Kenyon cells (KCs) of the fly brain synthesizes cAMP, which is believed to serve as the coincidence detector synergistically stimulated by calcium/calmodulin evoked by the odor reception and GS released in response to the dopamine signaling elicited by electric shock. However, live imaging analyses revealed that olfactory stimulation itself prompted the activation of dopaminergic neurons and resulted in the elevation of cAMP levels in KCs that received dopamine, regardless of calcium signaling. This finding raises questions about the longstanding and fundamental comprehension of conditioning mechanisms, as the cAMP levels in conditioned stimulus-positive (CS+) KCs could not be distinguished from those in the rest of the KCs. Our findings suggest that cAMP concentrations do not function as a mnemonic engram to CS+ neurons. Rather, the collective dynamics of cAMP are capable of integratively encoding the valence ascribed to odors being perceived at a given time. Furthermore, our investigation revealed that associative conditioning induces modifications in dopamine levels in response to both CS and US, resulting in alterations in cAMP levels. The increase in cAMP exerts a deleterious effect on the acetylcholine transmission from KCs. Accordingly, we postulate that, during conditioning, cAMP depresses KCs, thereby skewing the valence of the CS+ odor towards a more aversive state for the conditioned flies, and ultimately culminating in the formation of aversive memories.

neuroscience↗

bioRxiv2023

Antagonistic regulation of salt and sugar chemotaxis plasticity by a single chemosensory neuron in Caenorhabditis elegans

The nematode Caenorhabditis elegans memorizes various external chemicals, such as ions and odorants, during feeding. Here we find that C. elegans is attracted to the monosaccharides glucose and fructose after exposure to these monosaccharides in the presence of food; however, it avoids them without conditioning. The attraction to glucose requires a left-sided ASE gustatory neuron called ASEL. ASEL activity increases when glucose concentration decreases. Optogenetic ASEL stimulation promotes forward movements; however, after glucose conditioning, it promotes turning, suggesting that after glucose conditioning, the behavioral output of ASEL activation switches toward glucose. We previously reported that chemotaxis toward sodium ion (Na+), which is sensed by ASEL, increases after Na+ conditioning in the presence of food. Interestingly, glucose conditioning decreases Na+ chemotaxis, and conversely, Na+ conditioning decreases glucose chemotaxis, suggesting the reciprocal inhibition of learned chemotaxis to distinct chemicals. The activation of PKC-1, an nPKC {varepsilon}/{eta} ortholog, in ASEL promotes glucose chemotaxis and decreases Na+ chemotaxis after glucose conditioning. Furthermore, genetic screening identified ENSA-1, an ortholog of the protein phosphatase inhibitor ARPP-16/19, which functions in parallel with PKC-1 in glucose-induced chemotactic learning toward distinct chemicals. These findings suggest that kinase-phosphatase signaling regulates the balance between learned behaviors based on glucose conditioning in ASEL, which might contribute to migration toward chemical compositions where the animals were previously fed. Author summaryCaenorhabditis elegans responds to compounds that taste salty, bitter, sour, etc. However, its response to sweet compounds is unclear. Here, we show that C. elegans responds to glucose through a chemosensory neuron called ASEL. C. elegans avoids high concentrations of glucose and learns to approach glucose after feeding in the presence of high glucose, dependent on the action of ASEL. The ASEL neuron has been reported to respond to salt and promotes salt attraction after feeding in the presence of high salt. We find that the feeding-associated attractive responses to glucose and salt are antagonistic. When encountered with a mixture of salt and glucose during feeding, C. elegans changes its chemotactic response toward those chemicals according to the balance of each chemical in the mixture. C. elegans may memorize the concentrations of the chemical mixture during feeding and migrates to the chemical composition previously fed, which may promote opportunities obtaining food. Furthermore, we find that kinase-phosphatase signaling, which modulates neurotransmission, in ASEL is required for chemotaxis based on information processing of salt and glucose.

neuroscience↗