Kim, J.; Kang, T.; Song, D.; Yi, S.J. PADWQ Open-Source Project Repository. Available online: https://github.com/SJ-YI/PADWQ_open_source (accessed on 27 March 2021).

Bistable dynamics is a prominent feature of various types of neurons, such as thalamic neurons, sensory neurons, Purkinje cells and motor neurons [ 10, 81– 83]. Such bistable regimes involve the coexistence of different non-oscillatory stable states or different spiking modes, resting states and spiking, spiking and bursting. Detailed analyses also based on mathematical models [ 84– 86] not only showed that calcium current is involved in neuron bistability, as we found in our analysis, but also highlighted the role of the leak current in such behavior. Thus, we further analyzed RMD bistable response by varying the leakage current conductance at fixed .Modeled currents are potassium voltage-gated currents (SHL1, KVS1, SHK1, IRK, KQT3, EGL36, EGL2), calcium voltage-gated currents (EGL19, UNC2, CCA1), calcium-regulated potassium currents carried by big conductance channels (SLO1/SLO2 in combination with EGL19/UNC2) and small conductance channels (KCNL), sodium passive currents (NCA) and non-specific passive currents (LEAK). The majority of currents included in the model (voltage-gated potassium and calcium) are described with the standard mathematical formulation [ 24]: where x denotes a generic ion channel, V x represents the reversal potential for the current passing through the channel x, is the whole-cell maximal conductance associated with x, m x and h x denote activation and inactivation gating variables and the parameters p and q are assumed both equal to 1, unless stated otherwise. where K yx ( K xy) is linked to calcium affinity for channel closing (opening) transition, w yx ( w xy) regulates voltage sensitivity of closing (opening) transition, ( ) denotes the closing (opening) transition rate at 0 mV, and n yx ( n xy) represents the Hill coefficient of the closing (opening) transition. The activation time constant is a function of the same parameters, In this paper, we report, for the first time to the best of our knowledge, a comprehensive biophysical framework for the modeling of C. elegans neurons, which includes the main voltage-gated, ligand-gated and voltage/ligand-gated ion channels [ 13, 15, 17, 19, 36, 57] expressed in a large variety of neuronal and muscle cells in this nematode. In response to current pulses from 0 pA to 10 pA of 50 ms duration ( Fig 7B), RMD shows a threshold-like response, characterized by large excursions of membrane voltage, similarly to AWC ON ( Fig 4C). After stimulus removal, the membrane potential stabilizes at a depolarized state (−46.6 mV), in agreement with experimental data [ 13]. This effect is further discussed below and it is related to an interesting bistable behaviour of RMD.

Sodium (NCA) and non-specific leak currents (LEAK) are modeled as standard passive ohmic currents . A complete list of model equations for currents, steady-state activation and inactivation curves and time constant functions is given in Supplemental material (Eqs A-C in S1 File). Retirement plan participants and IRA owners, including owners of SEP IRAs and SIMPLE IRAs, are responsible for taking the correct amount of RMDs on time, every year from their accounts, and they may face stiff penalties for failure to take RMDs. For defined contribution plan participants, or IRA owners, who die after December 31, 2019, (with a delayed effective date for certain collectively bargained plans), the SECURE Act requires the entire balance of the participant's account be distributed within ten years. This 10-year rule has an exception for a surviving spouse, a child who has not reached the age of majority, a disabled or chronically ill person or a person not more than ten years younger than the employee or IRA account owner. The new 10-year rule applies regardless of whether the participant dies before, on, or after, the required beginning date. The required beginning date is the date an account owner must take their first RMD. The activation of BK channels is dependent on the state of nearby calcium channels [ 51, 52]. When CaV is closed, the opening probability for the corresponding BK channel is almost zero, since the calcium concentration inside the nanodomain is too low to cause a robust activation. The coupling between BK and CaV channel is modeled through the whole BK-CaV complex, for 1:1 stoichiometry [ 51], with the following equations for the opening probability and activation time constants: void set_pid_ROM( int8_t id, int8_t p_kp, int8_t p_ki, int8_t v_kp, int8_t v_ki, int8_t i_kp, int8_t i_ki);

Topics

where D Ca = 250 μm 2 s -1 is the calcium diffusion coefficient, r = 13 nm the radius of the nanodomain, F = 96485 C mol -1 the Faraday constant, is the intracellular buffer rate constant, [ B] tot = 30 μM is the total intracellular buffer concentration, assumed constant over time as required by the EBA. The values of the parameters mentioned above are taken from [ 51], due to the absence of specific data for C. elegans. i Ca is the calcium current through a single open voltage-gated calcium channel: An alternative theory suggests that the rhythmic movements help develop the vestibular system in young children, which can partially explain the high prevalence of RMD in infants. It has been seen that children who have underdeveloped vestibular systems benefit from performing RMD-like movements which stimulate the vestibular system [16] In SK channels, activation and inactivation are modulated by intracellular calcium transients in a microdomain surrounding the channel [ 50]. Since an exhaustive experimental characterization of cytosolic calcium transport and diffusion is still missing for C. elegans neurons, we model the calcium dynamics at the microscale based on a simplified mass balance equation [ 55, 68]. We take into account calcium inflow through voltage-sensitive channels ( I Ca) and outflow due to membrane exchangers removal, such as SERCA, Na +-Ca 2+ exchangers, and plasma membrane Ca 2+-ATPases [ 70]. In addition, we set an equilibrium concentration equal to a physiological baseline in zero current conditions, discarding source terms in case of current inversion to avoid concentrations lower than the baseline. This switching dynamics models compensatory cellular mechanisms avoiding too low intracellular calcium: Khan, H.; Kitano, S.; Frigerio, M.; Camurri, M.; Barasuol, V.; Featherstone, R.; Caldwell, D.G.; Semini, C. Development of the lightweight hydraulic quadruped robot—MiniHyQ. In Proceedings of the 2015 IEEE International Conference on Technologies for Practical Robot Applications (TePRA), Woburn, MA, USA, 11–12 May 2015; pp. 1–6. [ Google Scholar]