Tonic activity of metabotropic glutamate receptors is involved in developmental modification of short-term plasticity in the neocortex.
Maturation of many synapses of the CNS is characterized by a reduction in initial release probability and associated alterations in short-term plasticity (STP). We investigated the role of tonic activity of metabotropic glutamate receptors (mGluRs) in this process in glutamatergic synapses of rat neocortex. Consistent with previous reports, STP of excitatory postsynaptic currents (EPSCs) evoked by five-pulse stimulation was found to switch from depression at postnatal days 13-17 (P13-17) to facilitation at postnatal days 28-42 (P28-42). (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine, a specific mGluR2/3 agonist, strongly depressed EPSCs both at the early stage and the late stage of cortical development. This was accompanied by a switch from depression to facilitation of STP at the early stage and an increase in facilitation at the late stage. While application of 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl) propanoic acid (LY341495), an mGluR antagonist that is most potent at mGluR2/3, had no significant effect at the early stage, it significantly enhanced EPSC amplitude and reduced short-term facilitation at the late stage. Blocking glutamate transporter activity with l-trans-pyrrolidine-2,4-dicarboxylate (tPDC) significantly reduced EPSC amplitude and short-term depression in the younger group but had no effect in the older specimens. The effect of tPDC was blocked by LY341495. These results suggest that a progressive increase in tonic mGluR activity during postnatal development contributes to a reduction of release probability in excitatory cortical synapses. They also indicate that glutamate transporter activity in the neocortex decreases during postnatal development. This may play a role in increasing tonic activity of mGluRs by increasing ambient glutamate levels in the perisynaptic extracellular space.
Chen
Huan-Xin
HX
Dept. of Neurological Surgery, University of Florida, 100 South Newell Drive, Room L2-100, Gainesville, FL 32610, USA.
Roper
Steven N
SN
D000375:Aging / Q000378:metabolism*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D019579:Neocortex / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects; D013997:Time Factors; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes