Abstract：
:Spontaneous synchronized bursts of activity play an essential role in the maturation and plasticity of neuronal networks. To investigate the cellular properties that enable spontaneous network activity, we used dissociated cultures of hippocampal neurons that express prolonged network activity bursts. Acute exposure to a low concentration of N-methyl-d-aspartate (NMDA) caused an increase in spontaneous firing rates and intracellular calcium concentration ([Ca(2+)]i). However, in the course of a chronic (>1 day) exposure to NMDA, [Ca(2+)]i recovered back to normal baseline levels, and only sporadic asynchronous calcium transients were detected. Spontaneous network bursts were still absent 1 h after the removal of NMDA, indicating a persistent downregulation of network activity, which did recover eventually 2 days later. This effect of NMDA was activity-dependent as it was blocked by co-application of tetrodotoxin (TTX). The chronic NMDA-treated neurons expressed normal morphology and active membrane properties as well as spontaneous miniature excitatory postsynaptic currents and postsynaptic reactivity to glutamate. However, in response to trains of afferent stimulation in paired recordings, the treated neurons expressed synaptic depression as opposed to synaptic potentiation seen in control cells. Also, treated neurons did not respond to low-intensity electrical field stimulation as did control cells. Finally, Western blot analysis revealed that chronic exposure to NMDA altered presynaptic but not postsynaptic protein expression patterns, suggesting a presynaptic locus of effect. Thus a long-lasting increase in activity downregulates neurotransmitter release to prevent over-excitation of the network and, consequently, blocks the generation of network bursts.
journal_name
J Neurophysioljournal_title
Journal of neurophysiologyauthors
Cohen D,Segal Mdoi
10.1152/jn.91085.2008subject
Has Abstractpub_date
2009-04-01 00:00:00pages
2077-88issue
4eissn
0022-3077issn
1522-1598pii
91085.2008journal_volume
101pub_type
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