Abstract
Recent studies have focused attention on mechanisms of spontaneous large-scale wavelike activity during early development of the neocortex. In this study, we describe and characterize synchronous neuronal activity that occurs in cultured cortical networks naturally without pharmacological intervention. The synchronous activity that can be detected by means of Fluo-3 fluorescence imaging starts to develop at the beginning of the second week in culture and eventually includes the entire neuronal population about 1 wk later. A synchronous increase of [Ca2+]i in the neuronal population is associated with a burst of action potentials riding on a long-lasting depolarization recorded in a single cell. It is suggested that this depolarization results directly from synaptic current, which was comprised of at least three different components mediated by AMPA, N-methyl-d-aspartate (NMDA), and GABAA receptors. We never observed a gradually depolarizing pacemaker potential and found no evidence for a change of excitability during inter-burst periods. However, we found evidence for a period of synaptic depression after bursts. Network excitability recovers gradually over seconds from this depression that can explain the episodic nature of spontaneous network activity. Using pharmacological manipulation to investigate the propagation of activity in the network, we show that synchronous network activity depends on both glutamatergic and GABAAergic neurotransmission during a brief period. Reversal potential of GABAA receptor-mediated current was found to be significantly more positive than resting membrane potential both at 1 and 2 wk in culture, suggesting depolarizing action of GABA. However, in cultures older than 2 wk, inhibition of GABAAreceptors does not result in block of synchronous network activity but in modulation of burst width and frequency.
References
49
Referenced
153
10.1113/jphysiol.1993.sp019838
10.1016/S0166-2236(00)01813-0
10.1113/jphysiol.1989.sp017762
10.1016/0166-2236(91)90003-D
10.1113/jphysiol.1992.sp019290
10.1152/jn.1995.74.6.2713
10.1016/0006-8993(96)00052-2
10.1046/j.1460-9568.2002.01904.x
10.1002/(SICI)1096-9861(19970602)382:2<230::AID-CNE7>3.0.CO;2-4
10.1046/j.1460-9568.1999.00804.x
10.1016/S0896-6273(00)80724-2
10.1113/jphysiol.1988.sp016975
10.1016/0896-6273(89)90033-0
10.1111/j.1469-7793.1998.219bu.x
10.1038/74823
10.1152/jn.2000.84.5.2477
10.1111/j.1469-7793.1998.249bu.x
10.1016/S0306-4522(98)00666-6
10.1152/jn.1994.72.1.471
10.1523/JNEUROSCI.18-04-01419.1998
10.1016/0165-0270(94)00116-X
10.1152/jn.2000.83.2.808
10.1152/jn.2000.83.2.828
10.1113/jphysiol.1995.sp020882
10.1038/321519a0
10.1523/JNEUROSCI.15-10-06834.1995
10.1113/jphysiol.1987.sp016883
10.1523/JNEUROSCI.19-08-03007.1999
10.1023/A:1022571025830
10.1016/0896-6273(92)90074-N
10.1523/JNEUROSCI.12-12-04834.1992
10.1038/307462a0
10.1016/S0959-4388(99)80012-9
10.1523/JNEUROSCI.16-20-06414.1996
10.1523/JNEUROSCI.20-02-j0002.2000
10.1152/jn.2001.85.2.620
10.1152/jn.1993.70.4.1606
10.1038/651
10.1016/0304-3940(91)90310-P
10.1113/jphysiol.1992.sp019085
10.1046/j.0953-816x.2001.01636.x
10.1523/JNEUROSCI.21-22-08966.2001
10.1523/JNEUROSCI.20-08-03041.2000
10.1046/j.1460-9568.1999.00697.x
10.1111/j.1460-9568.1997.tb01449.x
10.1523/JNEUROSCI.21-22-08895.2001
10.1038/261720a0
10.1146/annurev.neuro.22.1.29
10.1126/science.1496379
Dates
Type | When |
---|---|
Created | 19 years, 3 months ago (May 30, 2006, 10:06 p.m.) |
Deposited | 5 years, 11 months ago (Sept. 8, 2019, 8:36 p.m.) |
Indexed | 3 days, 2 hours ago (Sept. 4, 2025, 10:11 a.m.) |
Issued | 22 years, 10 months ago (Nov. 1, 2002) |
Published | 22 years, 10 months ago (Nov. 1, 2002) |
Published Print | 22 years, 10 months ago (Nov. 1, 2002) |
@article{Opitz_2002, title={Spontaneous Development of Synchronous Oscillatory Activity During Maturation of Cortical Networks In Vitro}, volume={88}, ISSN={1522-1598}, url={http://dx.doi.org/10.1152/jn.00316.2002}, DOI={10.1152/jn.00316.2002}, number={5}, journal={Journal of Neurophysiology}, publisher={American Physiological Society}, author={Opitz, Thoralf and De Lima, Ana D. and Voigt, Thomas}, year={2002}, month=nov, pages={2196–2206} }