A Reconfiguration of Ca_V2 Ca²⁺ Channel Current and Its Dopaminergic D₂ Modulation in Developing Neostriatal Neurons

Abstract

. The modulatory effect of D 2 dopamine receptor activation on calcium currents was studied in neostriatal projection neurons at two stages of rat development: postnatal day (PD)14 and PD40. D 2 -class receptor agonists reduced whole cell calcium currents by about 35% at both stages, and this effect was blocked by the D 2 receptor antagonist sulpiride. Nitrendipine partially occluded this modulation at both stages, indicating that modulation of Ca V 1 channels was present throughout this developmental interval. Nevertheless, modulation of Ca V 1 channels was significantly larger in PD40 neurons. -Conotoxin GVIA occluded most of the Ca 2ϩ current modulation in PD14 neurons. However, this occlusion was greatly decreased in PD40 neurons. -Agatoxin TK occluded a great part of the modulation in PD40 neurons but had a negligible effect in PD14 neurons. The data indicate that dopaminergic D 2 -mediated modulation undergoes a change in target during development: from Ca V 2.2 to Ca V 2.1 Ca 2ϩ channels. This change occurred while Ca V 2.2 channels were being down-regulated and Ca V 2.1 channels were being up-regulated. Presynaptic modulation mediated by D 2 receptors reflected these changes; Ca V 2.2 type channels were used for release in young animals but very little in mature animals, suggesting that changes took place simultaneously at the somatodendritic and the synaptic membranes.

Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses

“…1E) of the ''unitary'' IPSCs recorded from SPN3SPN connections (Fig. 1F) was found (32,(40)(41)(42). First, shape index plots (graphing half widths vs. rise times) of mean IPSCs (GP3NSt, empty circles; SPN3SPN, filled circles) showed no significant differences between these two connections ( Fig.…”

“…IPSCs between SPNs were also recorded after antidromic stimulation of striofugal axons at the globus pallidus (GP) (called the GP3NSt connection to avoid confusion) ( Fig. 1 A) (32,(40)(41)(42) in the presence of glutamate receptor blockers (10 M CNQX plus 50 M APV). These responses were sensitive to 10 M bicuculline (Fig.…”

“…5A) (4,8,48). However, as in other cases, intrinsic quantal variability associated with unitary connections, and other factors, impeded a precise distinction between N (release sites) and P (release probability) (41,51). However, both parameters signal presynaptic mechanisms.…”

“…Calcium dynamics reflects the ''use'' or ''history'' of network activity (1)(2)(3)(4)(5)68). Therefore, presynaptic receptors can be conceived as sensors and regulators of the dynamics and computational properties of circuits, not simply as modifiers of synaptic strength (32,41,69,70).…”

Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons

“…In addition, enhancing Ca 2+ current through Ca V 1 channels would increase the number of action potentials fired to the same stimulus since these channels enhance the depolarization induced by the intracellular current step [5]. That is, in neurons with both A 1 and A 2A receptors, the actions of these receptors would be synergistic for excitability given their action on the different Ca 2+ currents [6,8,9,38,40,42,48]. This inference was also correct, since in about half of the neurons tested ( Fig.…”