Exploring Neuronal Bistability at the Depolarization Block

Many neurons display bistability–coexistence of two firing modes such as bursting and tonic spiking or tonic spiking and silence. Bistability has been proposed to endow neurons with richer forms of information processing in general and to be involved in short-term memory in particular by allowing a brief signal to elicit long-lasting changes in firing. In this paper, we focus on bistability that allows for a choice between tonic spiking and depolarization block in a wide range of the depolarization levels. We consider the spike-producing currents in two neurons, models of which differ by the parameter values. Our dopaminergic neuron model displays bistability in a wide range of applied currents at the depolarization block. The Hodgkin-Huxley model of the squid giant axon shows no bistability. We varied parameter values for the model to analyze transitions between the two parameter sets. We show that bistability primarily characterizes the inactivation of the Na+ current. Our study suggests a connection between the amount of the Na+ window current and the length of the bistability range. For the dopaminergic neuron we hypothesize that bistability can be linked to a prolonged action of antipsychotic drugs.

[1]  A. Hodgkin The local electric changes associated with repetitive action in a non‐medullated axon , 1948, The Journal of physiology.

[2]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[3]  J. Rinzel On repetitive activity in nerve. , 1978, Federation proceedings.

[4]  J. Rinzel,et al.  Control of repetitive firing in squid axon membrane as a model for a neuroneoscillator. , 1980, The Journal of physiology.

[5]  H Hultborn,et al.  Intrinsic membrane properties causing a bistable behaviour of alpha-motoneurones. , 1984, Experimental brain research.

[6]  Huxley Af,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952. , 1990 .

[7]  Steven H. Strogatz,et al.  Nonlinear Dynamics and Chaos , 2024 .

[8]  Germán Mato,et al.  Synchrony in Excitatory Neural Networks , 1995, Neural Computation.

[9]  C. Heckman,et al.  Influence of voltage-sensitive dendritic conductances on bistable firing and effective synaptic current in cat spinal motoneurons in vivo. , 1996, Journal of neurophysiology.

[10]  E Marder,et al.  Memory from the dynamics of intrinsic membrane currents. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. A. Baxter,et al.  Bistability and its regulation by serotonin in the endogenously bursting neuron R15 in Aplysia. , 1996, Journal of neurophysiology.

[12]  Anthony A. Grace,et al.  Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs , 1997, Trends in Neurosciences.

[13]  P. Rompré,et al.  Behavioral Evidence of Depolarization Block of Dopamine Neurons after Chronic Treatment with Haloperidol and Clozapine , 2000, The Journal of Neuroscience.

[14]  Bard Ermentrout,et al.  Simulating, analyzing, and animating dynamical systems - a guide to XPPAUT for researchers and students , 2002, Software, environments, tools.

[15]  J. Hounsgaard,et al.  Intrinsic membrane properties causing a bistable behaviour of α-motoneurones , 2004, Experimental Brain Research.

[16]  Andrey Shilnikov,et al.  Mechanism of bistability: tonic spiking and bursting in a neuron model. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[17]  Andrey Shilnikov,et al.  Coexistence of Tonic Spiking Oscillations in a Leech Neuron Model , 2005, Journal of Computational Neuroscience.

[18]  D. R. Verley,et al.  Bistable behavior originating in the axon of a crustacean motor neuron. , 2006, Journal of neurophysiology.

[19]  Charles J. Wilson,et al.  Transient high-frequency firing in a coupled-oscillator model of the mesencephalic dopaminergic neuron. , 2006, Journal of neurophysiology.

[20]  Anthony A Grace,et al.  Antipsychotic Drugs Rapidly Induce Dopamine Neuron Depolarization Block in a Developmental Rat Model of Schizophrenia , 2011, The Journal of Neuroscience.