Temperature is an unavoidable environmental cue that affects the metabolism and behavior of any creature on Earth, yet how animals perceive temperature is poorly understood. The nematode Caenorhabditis elegans "memorizes" temperatures, and this stored information modifies its subsequent migration along a temperature gradient. We show that the olfactory neuron designated AWC senses temperature. Calcium imaging revealed that AWC responds to temperature changes and that response thresholds differ depending on the temperature to which the animal was previously exposed. In the mutant with impaired heterotrimeric guanine nucleotide-binding protein (G protein)-mediated signaling, AWC was hyperresponsive to temperature, whereas the AIY interneuron (which is postsynaptic to AWC) was hyporesponsive to temperature. Thus, temperature sensation exhibits a robust influence on a neural circuit controlling a memory-regulated behavior.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. We previously showed that the expression of dynactin 1, an axon motor protein regulating retrograde transport, is markedly reduced in spinal motor neurons of sporadic ALS patients, although the mechanisms by which decreased dynactin 1 levels cause neurodegeneration have yet to be elucidated. The accumulation of autophagosomes in degenerated motor neurons is another key pathological feature of sporadic ALS. Since autophagosomes are cargo of dynein/dynactin complexes and play a crucial role in the turnover of several organelles and proteins, we hypothesized that the quantitative loss of dynactin 1 disrupts the transport of autophagosomes and induces the degeneration of motor neuron. In the present study, we generated a Caenorhabditis elegans model in which the expression of DNC-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model. Thus, our results suggest that decreased expression of dynactin 1 induces motor neuron degeneration and that the transport of autophagosomes is a novel and substantial therapeutic target for motor neuron degeneration.
Thermotaxis is a model to elucidate how nervous systems sense and memorize environmental conditions to regulate behavioral strategies in Caenorhabditis elegans. The genetic and neural imaging analyses revealed molecular and cellular bases of this experience-dependent behavior. Surprisingly, thermosensory neurons themselves memorize the sensed temperatures. Recently developed techniques for optical manipulation of neuronal activity have facilitated the revelation that there is a sophisticated information flow between sensory neurons and interneurons. Further studies on thermotaxis will allow us to understand the fundamental logics of neural processing from sensory perceptions to behavioral outputs.
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