Monday, October 19, 2009

Locations of neurotransmitter regulation

Being a fellow scientist interested in TRP (transient receptor potential) channels, I attended the talk, "Postsynaptic modulation of excitatory transmission via TRPV1 channels at a CNS synapse," presented by AE Chavez in the lab of Pablo Castillo.

I was delighted to hear such a well-rounded, complete talk. TRP channels comprise a huge family of membrane localized ion channels that are involved in numerous processes such as sensory processing (touch, taste, etc.), fear behavior, and sperm mobility. This talk in particular focused upon TRPV1 channels, which are non-selective channels activated by capsaicin and other lipophilic modulators. You may have thought about capsaicin the last time you ate a hot pepper.

Based upon previous data that demonstrated capsaicin's ability to increase mEPSC frequency in dorsal horn neurons of the PNS, the group wanted to further investigate whether capsaicin could have an effect in the CNS, specifically in the dentate gyrus.

Indeed, application of capsaicin caused a decrease in excitatory transmission. However, it's the location of this regulatory process that was so surprising.

Generally, TRPV1 channels are expressed presynaptically in the PNS; however, in the CNS, TRPV1 channels can be expressed postsynaptically. Analysis of mEPSC data demonstrated that capsaicin's effect on neurotransmission was occurring postsynaptically and, at that, was depressing AMPA currents but not NMDA currents. Loading the postsynaptic neuron with BAPTA showed that capsaicin's depressive effects are dependent upon Ca2+

They eventually found that this postsynaptic mechanism involved AMPA receptor internalization in a manner that is dependent upon Ca2+ and dynamin. Additionally, TRPV1 channels were implicated in a postsynaptic form of LTD. If TRPV1 channels are blocked, LTP is facilitated.

Postsynaptic regulation of neurotransmitter release always amazes me. It's reassuring to see such a good example of mutual dependency in the presynaptic-postsynaptic relationship. In addition to receptor internalization or delivery, sometimes it's a retrograde signaling molecule that lies at the heart of neurotransmitter control; for example, 12(S)HPETE at a particular CA3 neuron-interneuron synapse. Nitric oxide is another probable retrograde signal.

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