Astrocytic mGluR5 Modulation of Synaptic Transmission

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

9986954 McCarthy The goal of this proposal is to test the hypothesis that astrocytes dynamically modulate synaptic transmission within the CNS. A conditional knockout of the metabotropic glutamate receptor subtype 5 (mGluR5), a receptor subtype known to modulate synaptic transmission in the hippocampus, will be made. This receptor subtype is known to be important in the development of long term potentiation (LTP), a process thought to be involved in learning and memory. To accomplish this, the Cre/loxP system that enables gene knockout in a cellular and temporally-restricted manner will be used. Astrocytes comprise about 50% of the mammalian brain and their processes ensheathe most neuronal synapses. Historically, astrocytes generally have been considered to be passive cells primarily involved in maintaining an environment conducive for neuronal function. However, recent studies indicate that astrocytes in situ not only exhibit neurotransmitter receptors but also release neurotransmitters in a calcium-dependent manner. Several laboratories, including our own, have reported that astrocytes in situ respond to synaptically released neurotransmitter. Further, most neurotransmitters known to modulate synaptic efficacy activate astrocytic receptors in the same synaptic field. Importantly, a large percentage of the different neurotransmitters released in brain are involved in modulating synaptic transmission. The picture emerging is that astrocytes exhibit properties that would enable them to actively participate in synaptic transmission and play an important role in modulating synaptic transmission. A definitive demonstration that astrocytes in situ actively modulate synaptic transmission via a receptor-dependent process would markedly change our view of neurotransmission within brain.