PMID- 15182300 OWN - NLM STAT- MEDLINE DCOM- 20040802 LR - 20131121 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 19 IP - 11 DP - 2004 Jun TI - Irreversible loss of a subpopulation of cortical interneurons in the absence of glutamatergic network activity. PG - 2931-43 AB - In the cerebral cortex of mammals, gamma-aminobutyric acid (GABA)ergic neurons represent 15-25% of all neurons, depending on the species and area being examined. Because converging evidence suggests that activity may play an important role in the neuritic maturation and synaptic function of GABAergic neurons, it is feasible that activity plays a role in the regulation of the proportion of GABAergic neurons. Here we provide direct evidence that early in cortical development activity blockade may deplete the network of a subpopulation of GABA immunoreactive neurons characterized by their small size and late generation in vitro. In a period of time coinciding with the emergence of synchronous network activity, the survival and morphological differentiation of GABAergic neurons was influenced by long-term blockade of synaptic activity. While GABA(A) receptor antagonists had a minor promoting effect on interneuronal survival during the second week in vitro, antagonists of ionotropic glutamate receptors strongly impaired survival and differentiation of immature GABAergic interneurons. Interneuronal loss was more severe when N-methyl-D-aspartate receptors were blocked than after blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)/kainate receptors. The decrease in the density of GABAergic neurons was irreversible, but could be prevented by the simultaneous addition of brain-derived neurotrophic factor (BDNF). These results suggest that there is a narrow time window during neocortical development when glutamatergic activity, and specially NMDA receptor stimulation, is crucial to assure survival and maturation of a subpopulation of late developing GABAergic interneurons. FAU - de Lima, Ana Dolabela AU - de Lima AD AD - Otto-von-Guericke Universitat, Medizinische Fakultat, Institut fur Physiologie, 39120 Magdeburg, Germany. ana.delima@medizin.uni-magdeburg.de FAU - Opitz, Thoralf AU - Opitz T FAU - Voigt, Thomas AU - Voigt T LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Calbindin 2) RN - 0 (Calcium-Binding Proteins) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (GABA Antagonists) RN - 0 (Parvalbumins) RN - 0 (S100 Calcium Binding Protein G) RN - 124-87-8 (Picrotoxin) RN - 3KX376GY7L (Glutamic Acid) RN - 40709-69-1 (bicuculline methiodide) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione) RN - 76326-31-3 (2-amino-5-phosphopentanoic acid) RN - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) RN - HG18B9YRS7 (Valine) RN - SY7Q814VUP (Calcium) RN - Y37615DVKC (Bicuculline) SB - IM MH - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology MH - Age Factors MH - Animals MH - Apoptosis/drug effects/*physiology MH - Bicuculline/*analogs & derivatives/pharmacology MH - Calbindin 2 MH - Calcium/metabolism MH - Calcium-Binding Proteins/metabolism MH - Cell Count/methods MH - Cell Size/drug effects/physiology MH - Cells, Cultured MH - Cerebral Cortex/*cytology MH - Drug Interactions MH - Embryo, Mammalian MH - Excitatory Amino Acid Agonists/pharmacology MH - Excitatory Amino Acid Antagonists/pharmacology MH - GABA Antagonists/pharmacology MH - Glutamic Acid/*metabolism MH - Immunohistochemistry/methods MH - In Situ Nick-End Labeling/methods MH - Interneurons/classification/*cytology/metabolism MH - Nerve Net/cytology/*metabolism MH - Parvalbumins/metabolism MH - Picrotoxin/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - S100 Calcium Binding Protein G/metabolism MH - Time Factors MH - Valine/*analogs & derivatives/pharmacology MH - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology MH - gamma-Aminobutyric Acid/*metabolism EDAT- 2004/06/09 05:00 MHDA- 2004/08/03 05:00 CRDT- 2004/06/09 05:00 PHST- 2004/06/09 05:00 [pubmed] PHST- 2004/08/03 05:00 [medline] PHST- 2004/06/09 05:00 [entrez] AID - EJN3403 [pii] AID - 10.1111/j.0953-816X.2004.03403.x [doi] PST - ppublish SO - Eur J Neurosci. 2004 Jun;19(11):2931-43. doi: 10.1111/j.0953-816X.2004.03403.x.