Long-term depression in the developing hippocampus: low induction threshold and synapse nonspecificity.
It was observed that the use of paired-pulse afferent stimulation as test stimulation (0.1-0.02 Hz) in the hippocampal CA1 area in young (1-2 week) rats, but not in older ones, led to declining synaptic activity. We show that such very low-frequency stimulation leads to long-term depression (LTD) initiated by activation of NMDA receptor channels and/or T-type voltage-dependent calcium channels. The depression is initiated within three or four such stimuli, and <10 are sufficient to induce a notable long-term effect. When the paired-pulse stimulation exceeded threshold for postsynaptic spike activation, the depression was preceded by an NMDA receptor-dependent potentiation. Irrespective of whether homosynaptic potentiation or depression occurred, the paired pulse stimulation also induced depression in neighboring synapses alternately activated by single stimuli. These results point to a very high sensitivity for induction of synaptic depression during the neonatal period. They also support the notion that a brief rise in postsynaptic calcium can induce long-term potentiation (LTP) or LTD, a larger rise more likely to induce LTP, as well as that a prolonged modest increase produces selectively only LTD.
Wasling
Pontus
P
Institute of Physiology and Pharmacology, Göteborg University, SE-405 30 Göteborg, Sweden. pontus.wasling@physiol.gu.se
Hanse
Eric
E
Gustafsson
Bengt
B
D000375:Aging / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012684:Sensory Thresholds / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D016194:Receptors, N-Methyl-D-Aspartate