| Large-scale proteomic analyses of heterogeneous CNS preparations, such as isolated CNS synaptic vesicles, have provided a wealth of information related to synapse specific proteins and synaptic signaling pathways. However, these studies under-represent, or lack entirely, many vesicle and neurotransmitter signaling pathways. In particular, the neuromodulatory adrenergic and cholinergic pathways are often under-represented. In order to better understand the molecules and signaling pathways involved at cholinergic synapses, I have focused on the classic preparation of the electric lobe and electric organ of Torpedo californica. Many lines of evidence support the idea that in addition to acetylcholine, glutamate and ATP are also released from cholinergic synapses. Utilizing a single-vesicle imaging approach, I have found that individual synaptic vesicles from the electric ray possess neurotransmitter transporters for glutamate, ATP, and acetylcholine. These results help to explain neurotransmitter co-release at cholinergic terminals. In addition to classic neurotransmitter, I have discovered that synaptic vesicles in the peripheral nervous system (PNS) and the central nervous system (CNS) possess small ribonucleic acids, including transfer RNA fragments and microRNAs. This discovery suggests that, in addition to releasing neurotransmitters that can induce local changes in postsynaptic membrane polarization, synaptic vesicles may also release small RNAs that can directly regulate local protein synthesis at the postsynaptic cell. |
