Ectopic release sites lack fast vesicle recycling mechanisms, causing long-term depression of neuron-glial transmission in rat cerebellum.
Classical synaptic transmission occurs at active zones within the synaptic cleft, but increasing evidence suggests that vesicle fusion can also occur outside of these zones, releasing transmitter directly into the extrasynaptic space. The role of such "ectopic" release is unclear, but in the cerebellar molecular layer it is thought to guide the processes of Bergmann glia toward synaptic terminals through activation of glial α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptors. Once surrounding the terminal, the glial process is presumed to limit spillover of neurotransmitter between synapses by rapid uptake of glutamate. We have previously reported that this route for neuron-glial transmission exhibits long-term depression following repetitive stimulation at frequencies in the 0.1-1 Hz range, in ex vivo slices from rat cerebellum. Here, we present evidence that LTD arises because ectopic sites lack the fast recycling mechanisms that operate at the active zone. Consequently, ectopic vesicles constitute an exhaustible pool that is depleted at normal synaptic firing rates and only recovers slowly. This effect is cumulative, meaning that the strength of ectopic transmission provides a read-out of the average frequency of presynaptic firing over several minutes. Glial processes are therefore likely to interact most closely with terminals that fire infrequently; conditions that may promote elimination of, rather than support for, the connection.
Balakrishnan
Saju
S
Laboratory for Molecular Signalling, Babraham Institute, Babraham, Cambridge, United Kingdom.
Jackson
Claire
C
Russell
Noah
N
Bellamy
Tomas C
TC
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000502:physiology*