Neocortical long-term potentiation and long-term depression: site of expression investigated by infrared-guided laser stimulation.
The synaptic site of expression of long-term potentiation (LTP) and long-term depression (LTD) is still a matter of debate. To address the question of presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct approach, we measured the glutamate sensitivity of apical dendrites of layer 5 pyramidal neurons during LTP and LTD. We used infrared-guided laser stimulation to release glutamate from its "caged" form with high spatial and temporal resolution. Responses to photolytically released glutamate and synaptically evoked EPSPs were recorded with patch-clamp pipettes from the neuronal somata. LTP and LTD could be induced by electrical stimulation at the same synapses in succession. The NMDA receptor-dependent LTD was accompanied by a decrease in the dendritic glutamate sensitivity, suggesting a postsynaptic expression of neocortical LTD. In contrast, LTP was never accompanied by a change in the dendritic glutamate sensitivity. A possible explanation for this finding is a presynaptic expression of neocortical LTP. Another set of experiments corroborated these results: Photolytic application of glutamate with a frequency of 5 Hz caused a long-lasting Ca2+ and NMDA receptor-dependent decrease in the dendritic glutamate sensitivity. In contrast, LTP of dendritic glutamate sensitivity was never induced by photostimulation, despite several experimental modifications to prevent washout of the induction mechanism and to induce a stronger postsynaptic Ca2+ influx. In conclusion, our findings provide strong evidence for a postsynaptic expression of neocortical LTD and favor a primarily presynaptic locus of neocortical LTP.
Department of Clinical Neuropharmacology, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany. Eder@mpipsykl.mpg.de
Matthias
M
Eder
Walter
W
Zieglgänsberger
Hans-Ulrich
HU
Dodt
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005971:Glutamates / Q000494:pharmacology / Q000528:radiation effects; D066298:In Vitro Techniques; D007259:Infrared Rays; D007834:Lasers; D008027:Light; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000295:instrumentation / Q000379:methods; D010782:Photolysis; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012680:Sensitivity and Specificity; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays
C102508:(carboxy-2-nitrobenzyl)glutamic acid; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium