Bo Deng University of Nebraska-Lincoln Topics: Circuit Basics Circuit Models of Neurons --- FitzHuge-Nagumo Equations --- Hodgkin-Huxley Model --- Our Models Examples of Dynamics --- Bursting Spikes --- Metastability and Plasticity --- Chaos --- Signal Transduction Joint work with undergraduate and graduate students: Suzan Coons, Noah Weis, Adrienne Amador, Tyler Takeshita, Brittney Hinds, and Kaelly Simpson Circuit Basics Q = Q(t) denotes the net positive charge at a point of a circuit. I = dQ(t)/dt defines the current through a point. V = V(t) denotes the voltage across the point. Analysis Convention: When discussing current, we first assign a reference direction for the current I of each device. Then we have: I > 0 implies Q flows in the reference direction. I < 0 implies Q flows opposite the reference direction. Review of Elementary Components Capacitors A capacitor is a device that stores energy in an electric potential field. Q Inductors An inductor is a device that stores (kinetic) energy in a magnetic field. dI/dt Inductor dI d 2Q V L L 2 dt dt Resistors A resistor is an energy converting device. Two Types: Linear Obeying Ohm’s Law: V=RI, where R is resistance. Equivalently, I=GV with G = 1/R the conductance. Variable Having the IV – characteristic constrained by an equation g (V, I )=0. I g (V, I )=0 V Kirchhoff’s Voltage Law The directed sum of electrical potential differences around a circuit loop is 0. To apply this law: 1) 2) Choose the orientation of the loop. Sum the voltages to zero (“+” if its current is of the same direction as the orientation and “-” if current is opposite the orientation). Kirchhoff’s Current Law The directed sum of the currents flowing into a point is zero. To apply this law: 1) 2) Choose the directions of the current branches. Sum the currents to zero (“+” if a current points toward the point and “-” if it points away from the point). Example By Kirchhoff’s Voltage Law with Device Relationships and substitution to get or Circuit Models of Neurons I = F(V) 0 C 1 Excitable Membranes • Kandel, E.R., J.H. Schwartz, and T.M. Jessell Principles of Neural Science, 3rd ed., Elsevier, 1991. • Zigmond, M.J., F.E. Bloom, S.C. Landis, J.L. Roberts, and L.R. Squire Fundamental Neuroscience, Academic Press, 1999. Neuroscience: 3ed Hodgkin-Huxley Model Kirchhoff’s Current Law - I (t) -I (t) (Non-circuit) Models for Excitable Membranes • Morris, C. and H. Lecar, Voltage oscillations in the barnacle giant muscle fiber, Biophysical J., 35(1981), pp.193--213. • Hindmarsh, J.L. and R.M. Rose, A model of neuronal bursting using three coupled first order differential equations, Proc. R. Soc. Lond. B. 221(1984), pp.87--102. • Chay, T.R., Y.S. Fan, and Y.S. Lee Bursting, spiking, chaos, fractals, and universality in biological rhythms, Int. J. Bif. & Chaos, 5(1995), pp.595--635. • Izhikevich, E.M Neural excitability, spiking, and bursting, Int. J. Bif. & Chaos, 10(2000), pp.1171--1266. (also see his article in SIAM Review) Our Circuit Models Equations for Ion Pumps By Ion Pump Characteristics with substitution and assumption to get Dynamics of Ion Pump as Battery Charger Equivalent IV-Characteristics --- for parallel sodium channels Passive sodium current can be explicitly expressed as Equivalent IV-Characteristics --- for serial potassium channels Passive potassium current can be implicitly expressed as 0 A standard circuit technique to represent the hysteresis is to turn it into a singularly perturbed equation Examples of Dynamics --------- Bursting Spikes Metastability & Plasticity Chaotic Shilnikov Attractor Signal Transduction Geometric Method of Singular Perturbation Small Parameters: 0 < e << 1 with ideal hysteresis at e = 0 both C and l have independent time scales Rinzel & Wang (1997) Bursting Spikes C = 0.005 Metastability and Plasticity Terminology: A transient state which behaves like a steady state is referred to as metastable. A system which can switch from one metastable state to another metastable state is referred to as plastic. Metastability and Plasticity Neural Chaos C = 0.005 gNa = 1 dNa = - 1.22 v1 = - 0.8 v2 = - 0.1 ENa = 0.6 gK = 0.1515 dK = -0.1382 i1 = 0.14 i2 = 0.52 EK = - 0.7 C = 0.5 C = 0.5 l = 0.05 g = 0.18 e = 0.0005 Iin = 0 Myelinated Axon with Multiple Nodes Inside the cell Outside the cell Signal Transduction along Axons Neuroscience: 3ed Neuroscience: 3ed Neuroscience: 3ed Circuit Equations of Individual Node dV C C I I Na f K VC EK I A ext dt l I S VC g I A I A I S l I A VC g I A I e I V E h Na Na Na Na C Coupled Equations for Neighboring Nodes • Couple the nodes by adding a linear resistor between them 1 VC2 VC1 dVC 1 1 1 1 Iext I Na f K VC EK I A C R1 dt 1 dI A l I 1 V 1 g I 1 S C A dt 1 dI S l I 1A VC1 g I 1A dt 1 dI Na VC1 E1Na hNa I 1Na e dt dV 2 VC2 VC1 2 2 2 2 C C I Na f K VC EK I A R1 dt dI 2 A l I 2 V 2 g I 2 S C A dt dI 2 S l I 2 V 2 g I 2 A C A dt dI 2 Na V 2 E 2 h I 2 e Na Na Na C dt The General Case for N Nodes This is the general equation for the nth node In and out currents are derived in a similar manner: dVCn n1 I n f V n E n I n I n C Iout in Na K C K A dt dI An l I Sn VCn g I An dt dI Sn l I An VCn g I An dt n dI n h In e Na VCn ENa Na Na dt I if n 1 ext n1 n Iout V V n1 C C if n 1 n 1 R n1 n VC VC if 1 n N Iinn Rn if n N 0 C=.1 pF (x10 pF) C=.7 pF C=.7 pF Transmission Speed C=.1 pF C=.01 pF Closing Remarks: The circuit models can be further improved by dropping the serial connectivity of the passive electrical and diffusive currents. Existence of chaotic attractors can be rigorously proved, including junction-fold, Shilnikov, and canard attractors. Can be fitted to experimental data. Can be used to form neural networks. References: A Conceptual Circuit Model of Neuron, Journal of Integrative Neuroscience, 2009. Metastability and Plasticity of Conceptual Circuit Models of Neurons, Journal of Integrative Neuroscience, 2010.