Cadmium inhibits calcium activity in hippocampal CA1 neurons of freely moving mice

Cadmium (Cd) is a ubiquitous toxic heavy metal and a potential neurotoxicant due to its wide use in industrial manufacturing processes and commercial products, including fertilizers. The general population is exposed to Cd through food and smoking due to high transfer rates of Cd from contaminated soil. Cd has been shown to mimic calcium ions (Ca2+) and interfere with intracellular Ca2+ levels and Ca2+ signaling in in vitro studies. However, nothing is known about Cd's effects on Ca2+ activity in neurons in live animals. This study aimed to determine if Cd disrupts Ca2+ transients of neurons in CA1 region of the hippocampus during an associative learning paradigm. We utilized in vivo Ca2+ imaging in awake, freely moving C57BL/6 mice to measure Ca2+ activity in CA1 excitatory neurons expressing genetically encoded Ca2+ sensor GCaMP6 during an associative learning paradigm. We found that a smaller proportion of neurons are activated in Cd-treated groups compared with control during fear conditioning, suggesting that Cd may contribute to learning and memory deficit by reducing the activity of neurons. We observed these effects at Cd exposure levels that result in blood Cd levels comparable with the general U.S. population levels. This provides a possible molecular mechanism for Cd interference of learning and memory at exposure levels relevant to U.S. adults. To our knowledge, our study is the first to describe Cd effects on brain Ca2+ activity in vivo in freely behaving mice. This study provides evidence for impairment of neuronal calcium activity in hippocampal CA1 excitatory neurons in freely moving mice following cadmium exposure.