Glutamatergic Transmission And Dendrite Growth

Sensory stimuli and afferent innervation likely regulate dendrite growth through the primary excitatory neurotransmitter glutamate. The effects of glutamatergic synaptic transmission on dendrite growth have been studied using selective antagonists to the glutamatergic receptors subtypes NMDA and AMPA. Similar to studies of altered afferent innervation and TTX, various and, at times, contradictory results have been found. NMDA and AMPA receptor blockade reduces density and turnover of dendritic shaft filopodia in acute neonatal cortical brain slices13, and decreases the motility and length of filopodial on developing RGC dendrites in retinal explants26. In both of these studies, TTX produced different effects than glutamate receptor antagonists in the same preparations, highlighting the potential importance of low levels of spontaneous activity in promoting growth that is completely blocked by receptor antagonists. Studies examining long-term effects of antagonists on growth find that NMDA and AMPA receptor blockade decreases dendrite growth in pyramidal neurons of neonatal rat cortex organotypic cultures53 and tectal neurons in Xenopus tadpoles17'18, and NMDA receptor antagonists suppress dendrite growth in vivo in rat spinal motor neurons54 and supraoptic nucleus55. A developmental shift in glutamate receptor function in dendritogenesis has been shown through in vivo imaging of Xenopus tectum17,18. As developing tectal neurons elaborate dendritic arbors, the glutamatergic synapses on these dendrites undergo concomitant maturation56,57. Immature tectal neurons with small dendritic arbors express predominantly NMDA receptors at retinotectal synapses and express proportionally high levels of 'silent' synapses containing only NMDA receptors. Not surprisingly, at this stage, immature tectal neurons are susceptible to NMDA receptor antagonists, but not AMPA receptor blockade. As tectal neurons grow, AMPA receptors are incorporated into maturing glutamatergic synapses, and AMPA receptor antagonist-induced reduction in dendrite growth is seen. These results demonstrate that basal glutamatergic transmission contributes to dendrite growth and that different glutamate receptor subtypes mediate these influences at different stages of neuronal maturation. This developmental shift in glutamate receptor subtype expression may contribute to contradictory results from studies of receptor blockade on dendrite growth.

Glutamatergic transmission does not only underlie basal growth, but has also been shown to mediate activity-dependent dendritic growth. Both NMDA and AMPA receptor antagonists block filopodial stabilization and dendrite growth of Xenopus tectal neurons elicited by visual stimulation15. A direct effect of glutamate receptor stimulation on filopodia behavior was detected by time-lapse imaging of growing cortical pyramidal neurons in acute neonatal brain slices in response to local exogenous application of glutamate13. Glutamate released from a pipette in close proximity to dendritic shaft filopodia induced filopodial elongation. These filopodia may be detecting and growing toward the increasing glutamate gradient, and therefore may direct dendrite growth to presynaptic release sites.

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