Synaptic mechanisms of persistent reverberatory activity in neuronal networks.

Abstract:

:For brain functions such as working memory and motor planning, neuronal circuits are able to sustain persistent activity after transient inputs. Theoretical studies have suggested that persistent activity can exist in recurrently connected networks as active reverberation. However, the actual cellular processes underlying such reverberation are not well understood. In this study, we investigated the basic synaptic mechanisms responsible for reverberatory activity in small networks of rat hippocampal neurons in vitro. We found that brief stimulation of one neuron in a network could evoke, in an all-or-none fashion, reverberatory activity lasting for seconds. The reverberation was likely to arise from recurrent excitation because it was eliminated by partial inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (but not by blockade of NMDA receptors). In contrast, blocking inhibitory transmission with bicuculline enhanced the reverberation. Furthermore, paired-pulse stimuli with interpulse intervals of 200-400 ms were more effective than single pulses in triggering reverberation, apparently by eliciting higher levels of asynchronous transmitter release. Suppressing asynchronous release by EGTA-AM abolished reverberation, whereas elevating asynchronous release by strontium substantially enhanced reverberation. Finally, manipulating calcium uptake into or release from intracellular stores also modulated the level of reverberation. Thus, the oft-overlooked asynchronous phase of synaptic transmission plays a central role in the emergent phenomenon of network reverberation.

authors

Lau PM,Bi GQ

doi

10.1073/pnas.0500717102

keywords:

subject

Has Abstract

pub_date

2005-07-19 00:00:00

pages

10333-8

issue

29

eissn

0027-8424

issn

1091-6490

pii

0500717102

journal_volume

102

pub_type

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