Inhibitory Control of LTP and LTD: Stability of Synapse Strength

• Published in: Journal of neurophysiology 1999-04, Vol.81 (4), p.1559-1566
• Main Authors: Steele, Philip M, Mauk, Michael D
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Action Potentials - drug effects; Action Potentials - physiology; Animals; Electric Stimulation; Electrophysiology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; GABA Antagonists - pharmacology; gamma-Aminobutyric Acid - physiology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Neural Inhibition - physiology; Neuronal Plasticity - physiology; Picrotoxin - pharmacology; Pyramidal Cells - chemistry; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - physiology; Receptors, N-Methyl-D-Aspartate - physiology; Synapses - chemistry; Synapses - drug effects; Synapses - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.1999.81.4.1559

W. M. Keck Center for the Neurobiology of Learning and Memory; and the Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77030 Steele, Philip M. and Michael D. Mauk. Inhibitory control of LTP and LTD: stability of synapse strength. Although much is known about the induction of synaptic plasticity, the persistence of memories suggests the importance of understanding factors that maintain synaptic strength and prevent unwanted synaptic changes. Here we present evidence that recurrent inhibitory connections in the CA1 region of hippocampus may contribute to this task by modulating the relative ability to induce long-term potentiation and depression (LTP and LTD). Bath application of the -aminobutyric acid (GABA) type A agonist muscimol to hippocampal slices increased the range of frequencies that produce LTD, whereas in the presence of the GABA type A antagonist picrotoxin LTD was induced only at very low stimulation frequencies (0.25-0.5 Hz). Because one source of GABAergic input to CA1 pyramidal cells is via recurrent inhibition, we tested the prediction that elevated postsynaptic spike activity would increase feedback GABA inhibition and favor the induction of LTD. By using an induction stimulation of 8 Hz, which alone produced no net change in synaptic strength, we found that stimulation presented during antidromic activation of pyramidal cell spikes induced LTD. This effect was blocked by picrotoxin. The influence of recurrent inhibition on LTP and LTD displays properties that may decrease the potential for self-reinforcing, runaway changes in synapse strength. A mechanism of this sort may help maintain patterns of synaptic strengths despite the ongoing opportunities for plasticity produced by synapse activation.