Spillover-Mediated Transmission at Inhibitory Synapses Promoted by High Affinity α6 Subunit GABAA Receptors and Glomerular Geometry

synapses. Spillover of transmitter introduces a divergence of information flow superimposed on that produced by divergence in the wiring of synaptic connections. In the case of glutamate, it may also have significant implications for our understanding of the mechanisms Although a modulation of excitatory transmission by Summary GABA spillover has been observed in the hippocampus (Isaacson et al., 1993), little is known about whether Divergence and convergence of synaptic connections spillover-mediated transmission occurs at inhibitory syn-make a crucial contribution to the information pro-apses. We therefore studied inhibitory transmission at cessing capacity of the brain. Until recently, it was a synapse that seems anatomically specialized to pro-thought that transmitter released at a synapse af-mote spillover: the Golgi cell to granule cell synapse in fected only a specific postsynaptic cell. We show here the cerebellar cortex (Figures 1A and 1B), which has that spillover of inhibitory transmitter at the Golgi to been suggested to play a key role in regulating informa-granule cell synapse produces significant cross-talk tion processing by the cerebellum (Marr, 1969). This to non-postsynaptic cells, which is promoted both by synapse is localized within a glomerulus (Há mori and the anatomical specialization of this glomerular syn-apse and by the presence of the high affinity ␣ 6 subunit-1989). Each glomerulus is centered on the large, axonal containing GABA A receptor in granule cells. Cross-talk terminal of a glutamatergic mossy fiber afferent. The is manifested as a novel slow rising and decaying small mossy fiber terminal is surrounded by granule cell den-amplitude inhibitory postsynaptic current (IPSC) that drites that arise from 50–60 distinct granule cells, each can also contribute a long-lasting component to more of which sends a single dendrite to each glomerulus. typical IPSCs, which is prolonged by inhibition of the Intermingled with, but somewhat more peripheral to, this granule cell dendrite corona are numerous Golgi neuronal GABA transporter GAT-1. Because of the cell axon terminals that form GABAergic synapses with long duration of IPSCs generated by spillover, the total the granule cell dendrites. This mesh of dendritic and charge carried is three times that of IPSCs generated axonal processes is wrapped by a glial sheath. GABA by directly connected terminals. GABA spillover within released at Golgi to granule cell synapses is probably the mossy fiber glomerulus may play an important role confined within the glomerulus by the glial sheath, and in regulating the number of granule cells active in the …