Author:
Komendantov Alexander O.,Komendantova Olena G.,Johnson Steven W.,Canavier Carmen C.
Abstract
Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of N-methyl-d-aspartate (NMDA) and GABAA receptors is a crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking Ca2+-activated potassium SK channels can facilitate burst firing. A multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAA receptors as well as the modulation of the SK current on the firing activity. The simulated tonic activation of GABAA receptors was calibrated by taking into account the difference in the electrotonic properties in vivo versus in vitro. Although NMDA-evoked currents are required for burst generation in the model, currents evoked by GABAA-receptor activation can also regulate the firing pattern. For example, the model predicts that increasing the level of NMDA receptor activation can produce excessive depolarization that prevents burst firing, but a concurrent increase in the activation of GABAA receptors can restore burst firing. Another prediction of the model is that blocking the SK channel current in vivo will facilitate bursting, but not as robustly as blocking the GABAA receptors.
Publisher
American Physiological Society
Subject
Physiology,General Neuroscience
Reference87 articles.
1. Amini B, Clark JW, and Canavier CC. Calcium dynamics underlying pacemaker-like and burst firing in midbrain dopaminergic neurons: a computational study. J Neurophysiol 83: 2249-2261, 1999.
2. The GABA and substance P input to dopaminergic neurones in the substantia nigra of the rat
3. Properties and Plasticity of Excitatory Synapses on Dopaminergic and GABAergic Cells in the Ventral Tegmental Area
4. Brodie MS, McElvain MA, Bunney EB, and Appel SB. Pharmacological reduction of small conductance calcium-activated potassium current (SK) potentiates the excitatory effect of ethanol on ventral tegmental area dopamine neurons. J Pharmacol Exp Ther 290: 325-333, 1999.
Cited by
72 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献