Neurons in the brain continuously communicate with one another by secreting various types of neurotransmitters. Yet sometimes neuronal communication becomes disrupted, which is a major cause of psychiatric disease. A critical event leading to the release of neurotransmitters is the opening of voltage-gated calcium channels at presynaptic terminals. One such channel, the L-type, is implicated in bipolar disorder and schizophrenia. An unusual property of the L-type channel is that it does not participate in the release of neurotransmitters when an animal is in a “naïve” state, but does participate after new information is learned. Despite this insight, it has been unclear what holds the channel back and how it becomes recruited in the process of acquiring knowledge.
This study sought to fill that gap of information. It identified a signaling pathway triggered by the small GTPase enzyme, Rap1, which prevents L-type channels from being inserted into presynaptic terminals. When the researchers eliminated the Rap1-gene in primary cortical neurons, L-type channels were inserted into presynaptic terminals and boosted the release of neurotransmitter, showing that Rap1 is responsible for holding back L-type channels. This insight was demonstrated through the use of live imaging techniques and electron microscopy to visualize neurotransmitter release, calcium influx, and channel insertion into presynaptic terminals.
Alexei Morozov, PhD
The discovery of the signaling pathway that regulates L-type calcium channels will lead to a better understanding of many types of channel-related psychiatric disorders, such as bipolar disorder and schizophrenia.
Researchers were able to use live imaging techniques and electron microscopy to visualize the release of neurotransmitters between neurons directly.
Researchers will seek to determine whether the presence of a mental illness or the learning of new information alters the newly discovered signaling pathway.
Psychiatric disorders linked to a protein involved in the formation of long-term memories
Where to Find It:
Subramanian J, Dye L, Morozov A. Rap1 signaling prevents L-type calcium channel-dependent neurotransmitter release. J Neuroscience, 2013; 33(17):7245–52.