Effects of a Cav2.2 inhibitor on spatial and non-spatial short-term memory

Abstract

Neuronal voltage-gated calcium channels (VGCCs), including Cav2.1 and Cav2.2, mediate the presynaptic machinery responsible for vesicular release of neurotransmitters. However, the role of different VGCCs in neural circuits underlying spatial and non-spatial short-term memory remains poorly understood. Previous report has shown that Cav2.1-mediated signaling is required on spatial memory in a hippocampus-related object location test but has little effect on nonspatial memory in a perirhinal cortex-related object recognition test. Thus, Cav2.2-mediated functions need to be clarified. This study examined whether Cav2.2-mediated signaling plays a role in spatial and non-spatial short-term memory. Intracerebroventricular injection of the Cav2.2 inhibitor ω-conotoxin GVIA (5 pg/ side) in mice resulted in deficits in object location and recognition tests indicative of short-term memory. These results indicate that different VGCCs have different effects on memory performance.

Disruption of spatial cognition by intra-accumbens injection of Cav2.2 inhibitor

“…We have shown that Cav2.1-regulated glutamatergic signaling in the hippocampus [11] and NAc [12] is important in short-term spatial learning. We have also demonstrated the importance of hippocampal Cav2.2-regurated signaling in spatial short-term memory [13]. Previous reports have showed that Cav2.1 and Cav2.2 are present at high concentrations in the hippocampus and NAc [14] involved in spatial short-term memory formation.…”

Cav2.2-mediated NMDA receptor signaling in short-term memory

“…We showed that a subthreshold dose of CPP significantly decreased the spontaneous alteration behaviors when combined with a subthreshold dose of ω-conotoxin GVIA, although administration of CPP or ω-conotoxin GVIA alone was ineffective in the Y maze test [14,15,17]. The precise regulation of Ca 2+ signaling through Cav2.2 plays an important role in neuronal circuits [3].…”

“…We used 5mg/kg as a subthreshold dose of CPP in this study. On the other hand, among mice received intra-hippocampal or intraaccumbens injection of 0, 1, 5, or 10pg/side ω-conotoxin GVIA, mice received 5 or 10pg/side ω-conotoxin GVIA in both regions triggered a spatial short-term memory deficit [14,15]. To examine the effect of subthreshold doses of ω-conotoxin GVIA on Y-maze test, we injected 0, 0.1, 1, or 5pg/side ω-conotoxin GVIA into hippocampus or NAc.…”

“…The C57BL/6J mice were provided by Charles River Japan (Kanagawa, Japan). The mice were given free access to water and food pellets (CRF-1; Oriental Yeast Co. Ltd., Tokyo, Japan) and were housed under a 12/12-h light/dark cycle (lights on from 08:00 to 20:00) at 23 ± 1°C and [14,15,17]. In our previous study, we examined four groups of mice, including four groups each of mice that were given systemic injections of 0, 2.5, 5, or 10mg/kg CPP.…”

“…Our previous reports have showed that Cav2.1-regulated glutamatergic signaling in the hippocampus [12] and NAc [13] is important in short-term spatial learning. We have also demonstrated the importance of Cav2.2-regurated signaling in the hippocampus [14] and NAc [15] for spatial short-term memory. However, the role of Cav2.2-regurated glutamatergic signaling in the neural circuits underlying spatial short-term memory has not been studied.…”