Spontaneous Activity of Dopaminergic Retinal Neurons

Abstract

Dopaminergic local circuit neurons in the retina (DA cells) show robust, spontaneous, tetrodotoxin-sensitive pacemaking. To investigate the mechanism underlying this behavior, we characterized the sodium current and a subset of the potassium currents in the cells in voltage-clamp experiments. We found that there is a persistent component of the sodium current in DA cells which activates at more depolarized potentials than the transient component of the current. The transient component was completely inactivated at -50 mV, but DA cells remained able to fire spontaneous action potentials when potassium channels were partially blocked and the membrane potential remained above -40 mV. Based on these electrophysiological data, we developed a reduced computer model that reproduced the major features of DA cells. In simulations at the physiological resting potential, the persistent component of the sodium current was both necessary and sufficient to account for spontaneous activity, and the major contribution of the transient component of the sodium current was to initiate the depolarization of the model cell during the interspike interval. When tonic inhibition was simulated by lowering the input impedance of the model cell, the transient component played a larger role.

Differential distribution of voltage‐gated calcium channels in dopaminergic neurons of the rat retina

“…In those cells, it is found at presynaptic terminals and is known to mediate transmitter release (reviewed in Heidelberger et al, 2005). In the dopaminergic neuron, our localization of ␣1F channels to the dopaminergic perikaryon is consistent with patch clamp studies, which identify a high-voltage activated calcium channel as the predominant calcium fluxing channel of the dopaminergic cell body (Steffen et al, 2003) and with the finding that dihydropyridine antagonists inhibit dopamine release from the perikaryon (Puopolo et al, 2001). Tamura et al (1995) found that dihydropyridine antagonists inhibited retinal dopamine release by about 10%, consistent with a minor role for the dopaminergic perikarya in overall release of dopamine.…”

Roles of Subthreshold Calcium Current and Sodium Current in Spontaneous Firing of Mouse Midbrain Dopamine Neurons

“…These oscillations are calcium-dependent and, at least in some cases, occur at a frequency similar to the frequency of spontaneous firing of full-blown spikes under control conditions, as if normal pacemaking is driven by an underlying oscillation whose depolarizing phase is entirely attributable to calcium current. In a variety of other types of pacemaking neurons, including dopaminergic neurons in the retina and in the olfactory bulb (Feigenspan et al, 1998;Steffen et al, 2003;Puopolo et al, 2005), there appears to be a strong contribution from subthreshold "persistent" sodium current to the spontaneous depolarization between spikes. It has been argued that subthreshold persistent sodium current might necessarily be present in all neurons that have large transient sodium currents (Taddese and Bean, 2002) (but see Astman et al, 2006).…”

Voltage-Gated Sodium Channels Improve Contrast Sensitivity of a Retinal Ganglion Cell

“…However, the experimental paradigm used here was designed to minimize the effect of one contrast on the response to the next by presenting different contrasts in a random sequence separated by 3-5 s of the stimulus-off period and by discarding the first trial in the next block of trials (see Materials and Methods). A related possibility is that TTX, by blocking spiking activity in the dopaminergic amacrine cell and thus the release of dopamine (Steffen et al, 2003), might reduce specific adaptational effects of dopamine at high contrasts on Na ϩ channels (Hayashida and Ishida, 2004), thereby enhancing responses. This possibility seems unlikely, because dopamine diffuses slowly throughout the retina and thus with a stimulus protocol designed to reduce adaptational effects would persist for all contrasts.…”