Retrieval of Context-Associated Memory is Dependent on the Cav3.2 T-Type Calcium Channel

Abstract

Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of this channel in learning and memory, we subjected Cav3.2 homozygous and heterozygous knockout mice and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning, the Morris water-maze and passive avoidance. The Cav3.2 −/− mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2 +/− mice, whereas LTP persisted for only 120 minutes in Cav3.2 −/− mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes, we next performed experiments to knock down local function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil, a T-type channel blocker, exhibited similar behaviors as homozygous knockouts. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel.

The Novel Cognitive Enhancer ST101 Enhances Acetylcholine Release in Mouse Dorsal Hippocampus Through T-type Voltage-Gated Calcium Channel Stimulation

“…However, synapsin I expression in cholinergic nerve terminals has not reported. Chen et al (29) reported that mibefradil infusion into the hippocampus impairs retrieval of context-associated memory. Taken together, activation of T-type VGCCs likely have a critical role in the improvement of hippocampus-dependent memory functions in neurodegenerative diseases.…”

Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system: news from the world of knockout mice

“…The first report about T-type channels and vasodilation came from the group of Kevin Campbell (14). They demonstrated abnormal relaxation in response to ACh and a NO donor.…”

“…(14,60). Unfortunately, both models have neurological defects that have to be kept in mind when studying the cardiovascular system.…”

“…Unfortunately, both models have neurological defects that have to be kept in mind when studying the cardiovascular system. T-type channels are now known to be involved in vascular function being involved in ACh-induced relaxation of coronary and cerebral arteries (Ca v 3.2) (14,36) and contractility in mesenteric and pulmonary vessels (Ca v 3.1) (111). Furthermore, these channels regulate heart rate (Ca v 3.1) (67).…”

Amygdala and Taste Learning

“…In this sense, the hippocampus and the amygdala appear to be specifically involved in the contextual effects on conditioning, depending on the type of learning paradigm. The hippocampus seems to be involved in memory processes and contextual learning [136], mainly in the paradigm of fear conditioning and in spatial tasks, such as the Morris water-maze [137][138][139]. Some reports also suggest that the amygdala is part of the brain mechanism that allows the context to influence fear conditioning [140][141][142] and place conditioning [143].…”