PMID- 18339694 OWN - NLM STAT- MEDLINE DCOM- 20080604 LR - 20211020 IS - 1469-7793 (Electronic) IS - 0022-3751 (Print) IS - 0022-3751 (Linking) VI - 586 IP - 9 DP - 2008 May 1 TI - Emergence of brain-derived neurotrophic factor-induced postsynaptic potentiation of NMDA currents during the postnatal maturation of the Kolliker-Fuse nucleus of rat. PG - 2331-43 LID - 10.1113/jphysiol.2007.148916 [doi] AB - The Kolliker-Fuse nucleus (KF) contributes essentially to respiratory pattern formation and adaptation of breathing to afferent information. Systems physiology suggests that these KF functions depend on NMDA receptors (NMDA-R). Recent investigations revealed postnatal changes in the modulation of glutamatergic neurotransmission by brain-derived neurotrophic factor (BDNF) in the KF. Therefore, we investigated postnatal changes in NMDA-R subunit composition and postsynaptic modulation of NMDA-R-mediated currents by BDNF in KF slice preparations derived from three age groups (neonatal: postnatal day (P) 1-5; intermediate: P6-13; juvenile: P14-21). Immunohistochemistry showed a developmental up-regulation of the NR2D subunit. This correlated with a developmental increase in decay time of NMDA currents and a decline of desensitization in response to repetitive exogenous NMDA applications. Thus, developmental up-regulation of the NR2D subunit, which reduces the Mg(2+) block of NMDA-R, causes these specific changes in NMDA current characteristics. This may determine the NMDA-R-dependent function of the mature KF in the control of respiratory phase transition. Subsequent experiments revealed that bath-application of BDNF progressively potentiated these repetitively evoked NMDA currents only in intermediate and juvenile age groups. Pharmacological inhibition of protein kinase C (PKC), as a downstream component of the BDNF-tyrosine kinase B receptor (trkB) signalling, prevented BDNF-induced potentiation of NMDA currents. BDNF-induced potentiation of NMDA currents in later developmental stages might be essential for synaptic plasticity during the adaptation of the breathing pattern in response to peripheral/central commands. The lack of plasticity in neonatal neurones strengthens the hypothesis that the respiratory network becomes permissive for activity-dependent plasticity with ongoing postnatal development. FAU - Kron, Miriam AU - Kron M AD - Department of Neuro and Sensory Physiology, University Medicine Gottingen, Georg August University, Humboldtallee 23, 37073 Gottingen, Germany. FAU - Reuter, Julia AU - Reuter J FAU - Gerhardt, Ellen AU - Gerhardt E FAU - Manzke, Till AU - Manzke T FAU - Zhang, Weiqi AU - Zhang W FAU - Dutschmann, Mathias AU - Dutschmann M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080313 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (NR2B NMDA receptor) RN - 0 (NR2D NMDA receptor) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Aging/drug effects/*physiology MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Excitatory Postsynaptic Potentials/drug effects/*physiology MH - Ion Channel Gating/drug effects/physiology MH - Long-Term Potentiation/drug effects/*physiology MH - Pons/drug effects/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*metabolism PMC - PMC2479556 EDAT- 2008/03/15 09:00 MHDA- 2008/06/05 09:00 PMCR- 2009/05/01 CRDT- 2008/03/15 09:00 PHST- 2008/03/15 09:00 [pubmed] PHST- 2008/06/05 09:00 [medline] PHST- 2008/03/15 09:00 [entrez] PHST- 2009/05/01 00:00 [pmc-release] AID - jphysiol.2007.148916 [pii] AID - 10.1113/jphysiol.2007.148916 [doi] PST - ppublish SO - J Physiol. 2008 May 1;586(9):2331-43. doi: 10.1113/jphysiol.2007.148916. Epub 2008 Mar 13.