The brain stores information in patterns of synaptic connections within large networks of neurons. New information is incorporated into a neural network through the modification of connections via mechanisms that are incompletely understood. One fundamental question is whether individual connections behave independently, or whether they are influenced by the activity of neighboring synapses. Synaptic connections are made through the release of diffusible neurotransmitter molecules that bind to receptors on the recipient neuron; recent evidence suggests that the neurotransmitter may escape the synapse in which it is released and diffuse into neighboring synapses. This """"""""spillover"""""""" of neurotransmitter between synaptic connections would have a profound impact on the information capacity of neural networks and the mechanisms by which they are constructed during development. Work in this laboratory is directed towards determining whether the excitatory neurotransmitter glutamate spills over between synapses in the hippocampus, a major site of learning and memory storage in the brain, and in the retina, where visual stimuli is encoded for transmission along the optic nerve.Using electrophysiological techniques in acutely prepared slices of rat retina and hippocampus, we have found that glutamate escapes the synapse from which it is released and diffuses into neighboring synapses. This diffusion is tightly regulated by glutamate transporters, pump proteins located primarily on glial membranes that bind glutamate and remove it from the cerebrospinal fluid. Moreover, it appears that the electrical state of the recipient neuron influence whether the receptors are responsive to low levels of glutamate released from a distant synapse. Work is continuing to investigate the modulation of these mechanisms and their impact on information processing in networks of neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002986-01
Application #
6413860
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Scimemi, Annalisa (2013) A TRP among the astrocytes. J Physiol 591:9-15
Scimemi, Annalisa; Meabon, James S; Woltjer, Randall L et al. (2013) Amyloid-?1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. J Neurosci 33:5312-8
Scimemi, Annalisa; Diamond, Jeffrey S (2012) The number and organization of Ca2+ channels in the active zone shapes neurotransmitter release from Schaffer collateral synapses. J Neurosci 32:18157-76
Singer, Joshua H; Diamond, Jeffrey S (2006) Vesicle depletion and synaptic depression at a mammalian ribbon synapse. J Neurophysiol 95:3191-8
Diamond, Jeffrey S (2006) Astrocytes put down the broom and pick up the baton. Cell 125:639-41
Zhang, Jun; Diamond, Jeffrey S (2006) Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina. J Comp Neurol 498:810-20
Diamond, Jeffrey S (2005) Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: transmitter uptake gets faster during development. J Neurosci 25:2906-16
Mathews, Gregory C; Diamond, Jeffrey S (2003) Neuronal glutamate uptake Contributes to GABA synthesis and inhibitory synaptic strength. J Neurosci 23:2040-8