A hyperpolarizing neuron recruits undocked innexin hemichannels to transmit neural information in Caenorhabditis elegans.

While depolarization of the neuronal membrane is known to evoke the neurotransmitter release from synaptic vesicles, hyperpolarization is regarded as a resting state of chemical neurotransmission. Here, we report that hyperpolarizing neurons can actively signal neural information by employing undocked hemichannels. We show that UNC-7, a member of the innexin family in Caenorhabditis elegans, functions as a hemichannel in thermosensory neurons and transmits temperature information from the thermosensory neurons to their postsynaptic interneurons. By monitoring neural activities in freely behaving animals, we find that hyperpolarizing thermosensory neurons inhibit the activity of the interneurons and that UNC-7 hemichannels regulate this process. UNC-7 is required to control thermotaxis behavior and functions independently of synaptic vesicle exocytosis. Our findings suggest that innexin hemichannels mediate neurotransmission from hyperpolarizing neurons in a manner that is distinct from the synaptic transmission, expanding the way of neural circuitry operations.

AWC thermosensory neuron interferes with information processing in a compact circuit regulating temperature-evoked posture dynamics in the nematode Caenorhabditis elegans.

Elucidating how individual neurons encode and integrate sensory information to generate a behavior is crucial for understanding neural logic underlying sensory-dependent behavior. In the nematode Caenorhabditis elegans, information flow from sensory input to behavioral output is traceable at single-cell level due to its entirely solved neural connectivity. C. elegans processes the temperature information for regulating behavior consisting of undulatory posture dynamics in a circuit including two thermosensory neurons AFD and AWC, and their postsynaptic interneuron AIY. However, how the information processing in AFD-AWC-AIY circuit generates the posture dynamics remains elusive. To quantitatively evaluate the posture dynamics, we introduce locomotion entropy, which measures bandwidth of the frequency spectrum of the undulatory posture dynamics, and assess how the motor pattern fluctuates. We here found that AWC disorders the information processing in AFD-AWC-AIY circuit for regulating temperature-evoked posture dynamics. Under slow temperature ramp-up, AWC adjusts AFD response, whereby broadening the temperature range in which animals exhibit fluctuating posture undulation. Under rapid temperature ramp-up, AWC increases inter-individual variability in AIY activity and the fluctuating posture undulation. We propose that a compact nervous system recruits a sensory neuron as a fluctuation inducer for regulating sensory-dependent behavior.

OLA-1, an Obg-like ATPase, integrates hunger with temperature information in sensory neurons in C. elegans.

Animals detect changes in both their environment and their internal state and modify their behavior accordingly. Yet, it remains largely to be clarified how information of environment and internal state is integrated and how such integrated information modifies behavior. Well-fed C. elegans migrates to past cultivation temperature on a thermal gradient, which is disrupted when animals are starved. We recently reported that the neuronal activities synchronize between a thermosensory neuron AFD and an interneuron AIY, which is directly downstream of AFD, in well-fed animals, while this synchrony is disrupted in starved animals. However, it remained to be determined whether the disruption of the synchrony is derived from modulation of the transmitter release from AFD or from the modification of reception or signal transduction in AIY. By performing forward genetics on a transition of thermotaxis behavior along starvation, we revealed that OLA-1, an Obg-like ATPase, functions in AFD to promote disruption of AFD-AIY synchrony and behavioral transition. Our results suggest that the information of hunger is delivered to the AFD thermosensory neuron and gates transmitter release from AFD to disrupt thermotaxis, thereby shedding light onto a mechanism for the integration of environmental and internal state to modulate behavior.

Neural Coding of Thermal Preferences in the Nematode Caenorhabditis elegans.

Animals are capable to modify sensory preferences according to past experiences. Surrounded by ever-changing environments, they continue assigning a hedonic value to a sensory stimulus. It remains to be elucidated however how such alteration of sensory preference is encoded in the nervous system. Here we show that past experiences alter temporal interaction between the calcium responses of sensory neurons and their postsynaptic interneurons in the nematode Caenorhabditis elegansC. elegans exhibits thermotaxis, in which its temperature preference is modified by the past feeding experience: well-fed animals are attracted toward their past cultivation temperature on a thermal gradient, whereas starved animals lose that attraction. By monitoring calcium responses simultaneously from both AFD thermosensory neurons and their postsynaptic AIY interneurons in well-fed and starved animals under time-varying thermal stimuli, we found that past feeding experiences alter phase shift between AFD and AIY calcium responses. Furthermore, the difference in neuronal activities between well-fed and starved animals observed here are able to explain the difference in the behavioral output on a thermal gradient between well-fed and starved animals. Although previous studies have shown that C. elegans executes thermotaxis by regulating amplitude or frequency of the AIY response, our results proposed a new mechanism by which thermal preference is encoded by phase shift between AFD and AIY activities. Given these observations, thermal preference is likely to be computed on synapses between AFD and AIY neurons. Such a neural strategy may enable animals to enrich information processing within defined connectivity via dynamic alterations of synaptic communication.

Age-dependent changes in response property and morphology of a thermosensory neuron and thermotaxis behavior in Caenorhabditis elegans.

Age-dependent cognitive and behavioral deterioration may arise from defects in different components of the nervous system, including those of neurons, synapses, glial cells, or a combination of them. We find that AFD, the primary thermosensory neuron of Caenorhabditis elegans, in aged animals is characterized by loss of sensory ending integrity, including reduced actin-based microvilli abundance and aggregation of thermosensory guanylyl cyclases. At the functional level, AFD neurons in aged animals are hypersensitive to high temperatures and show sustained sensory-evoked calcium dynamics, resulting in a prolonged operating range. At the behavioral level, senescent animals display cryophilic behaviors that remain plastic to acute temperature changes. Excessive cyclase activity of the AFD-specific guanylyl cyclase, GCY-8, is associated with developmental defects in AFD sensory ending and cryophilic behavior. Surprisingly, loss of the GCY-8 cyclase domain reduces these age-dependent morphological and behavioral changes, while a prolonged AFD operating range still exists in gcy-8 animals. The lack of apparent correlation between age-dependent changes in the morphology or stimuli-evoked response properties of primary sensory neurons and those in related behaviors highlights the importance of quantitative analyses of aging features when interpreting age-related changes at structural and functional levels. Our work identifies aging hallmarks in AFD receptive ending, temperature-evoked AFD responses, and experience-based thermotaxis behavior, which serve as a foundation to further elucidate the neural basis of cognitive aging.

Multistage slow relaxation in a Hamiltonian system: The Fermi-Pasta-Ulam model.

The relaxation process toward equipartition of energy among normal modes in a Hamiltonian system with many degrees of freedom, the Fermi-Pasta-Ulam (FPU) model is investigated numerically. We introduce a general indicator of relaxation σ which denotes the distance from equipartition state. In the time evolution of σ, some long-time interferences with relaxation, named "plateaus," are observed. In order to examine the details of the plateaus, relaxation time of σ and excitation time for each normal mode are measured as a function of the energy density ε0=E0/N. As a result, multistage relaxation is detected in the finite-size system. Moreover, by an analysis of the Lyapunov spectrum, the spectrum of mode energy occupancy, and the power spectrum of mode energy, we characterize the multistage slow relaxation, and some dynamical phases are extracted: quasiperiodic motion, stagnant motion (escaping from quasiperiodic motion), local chaos, and stronger chaos with nonthermal noise. We emphasize that the plateaus are robust against the arranging microscopic state. In other words, we can often observe plateaus and multistage slow relaxation in the FPU phase space. Slow relaxation is expected to remain or vanish in the thermodynamic limit depending on indicators.