Book of Abstracts 18 National Meeting of the British Neuroscience Association

Considerable progress has been made recently in the understanding of the cellular and molecular mechanisms that underlie the coupling between neuronal activity and glucose utilization by the brain. A central role in this coupling is played by astrocytes, which are strategically positioned through (a) processes that largely ensheath synapses and express receptors and reuptake sites for various neurotransmitters including glutamate and (b) through other processes, the astrocytic end-feet, which surround intraparenchymal capillaries and express, among other molecules, glucose transporters. The essential steps in this coupling involve the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase. This process triggers glucose uptake and its glycolytic processing, resulting in the release of lactate from astrocytes, which fuels the neuronal energy demands associated with synaptic transmission. A large body of in vitro and in vivo experimental evidence from our group as well as from others, supports this model often referred to as "the astrocyte-neuron lactate shuttle" (1-5). This body of evidence provides a molecular and cellular basis for interpreting data obtained with functional brain imaging studies. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission. AMPARs containing the GluR-B subunit are expressed in principal neurons and exhibit voltage-independent gating and lack of Ca2+-permeability. These properties derive from the particular pore loop sequence (Q/R site) of GluR-B, which contains an arginine residue resulting from RNA editing. Preventing Q/R site editing of transcripts from only one GluR-B allele remarkably results in epilepsy. Forebrain expression of unedited GluR-B and GluR-B ablation strikingly enhance odor discrimination, probably by increased Ca2+ influx and lateral inhibition at dendrodendritic olfactory bulb synapses. Olfactory memory however is impaired relative to wild type, and the impairment correlates with the extent of GluR-B loss in hippocampus and cortex, but not olfactory bulb. Transgenic expression of GFP-tagged GluR-B in piriform cortex rescues memory, indicating that the olfactory bulb is necessary for odor discrimination but not for olfactory memory. The main partner subunit of GluR-B in principal neurons is GluR-A. Adult GluR-A knockout mice lack tetanus-induced field LTP in CA3-to-CA1 cell connections, but exhibit delayed LTP in a theta-burst paradigm, ultimately reaching wild-type levels. Notably, these mice are profoundly impaired in spatial working but not reference memory. Moreover, a conditional learning task revealed the importance of GluR-A dependent synaptic plasticity in memory systems encoding both spatial and temporal contexts associated with a particular event. BNA'05_abstracts.doc 4 3.01 Developmental expression of immunocytochemical markers in …