Behavioral forgetting of olfactory learning is mediated by interneuron-regulated network plasticity in Caenorhabditis elegans .

Forgetting is important for animals to manage acquired memories to enable adaptation to changing environments; however, the neural network in mechanisms of forgetting is not fully understood. To understand the mechanisms underlying forgetting, we examined olfactory adaptation, a form of associative learning, in (). The forgetting of diacetyl olfactory adaptation in is regulated by secreted signals from AWC sensory neurons via the TIR-1/JNK-1 pathway. These signals cause a decline of the sensory memory trace in AWA neurons where diacetyl is mainly sensed. To further understand the neural network that regulates this forgetting, we investigated the function of interneurons downstream of AWA and AWC neurons. We found that a pair of interneurons, AIA, is indispensable for the proper regulation of behavioral forgetting of diacetyl olfactory adaptation. Loss of or inactivation of AIA caused the impairment of the chemotaxis recovery after adaptation without causing severe chemotaxis defects in naïve animal. AWA Ca imaging analyses suggested that loss or inactivation of AIA interneurons did not affect the decline of the sensory memory trace after the recovery. Furthermore, AIA responses to diacetyl were observed in naïve and after the recovery, but not just after the conditioning, suggesting that AIA responses after the recovery are required for the chemotaxis to diacetyl. We propose that the functional neuronal circuit for attractive chemotaxis to diacetyl is changed temporally at the recovery phase so that AIA interneurons are required for chemotaxis, although AIAs are dispensable for attractive chemotaxis to diacetyl in naïve animals.Forgetting is important to enable animals to adapt to changing environments; however, the mechanisms of forgetting are poorly understood at the molecular and cellular levels. In this study, we found that a pair of interneurons in the olfactory circuit of are indispensable for behavioral forgetting, but not for regulation of the sensory memory trace, in simple olfactory learning. These findings suggest that neuronal circuits are important for regulating forgetting by managing memory and also for the generation of appropriate behavioral responses.