Endogenous Zn2+ is required for the induction of long-term potentiation at rat hippocampal mossy fiber-CA3 synapses

• Published in: Synapse (New York, N.Y.) Vol. 38; no. 2; pp. 187 - 197
• Main Authors: Lu, You-Ming, Taverna, Franco A., Tu, Rita, Ackerley, Cameron A., Wang, Yu-Tian, Roder, John
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.11.2000
• Subjects: hippocampus; long-term potentiation; mossy fiber-CA3 synapse; Zn2; Zn2+ chelator; Zn2+-deficient rat
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/1098-2396(200011)38:2<187::AID-SYN10>3.0.CO;2-R

The functional role of the abundant Zn2+ found in some hippocampal synapses has been an enigma. We show here, using N‐[6‐methoxy‐8‐quinolyl]‐P‐toluenesulfonamide (TSQ) staining, that chelatable‐Zn2+ can be removed from hippocampal synaptic boutons using dietary depletion or with Zn2+ chelators. A chronic dietary deficiency of bouton Zn2+ resulted in the impairment of long‐term potentiation (LTP) at mossy fiber‐CA3 synapses. The averaged normalized fEPSP slope 30 min after tetanus was 209 ± 28% of baseline value in control (mean ± SEM, n = 10), and 118 ± 12% in Zn2+‐deficient rats (mean ± SEM, n = 12, P < 0.01). In the deficient rats with Zn2+ supplements, mossy fiber LTP returned to normal levels. The acute depletion of bouton Zn2+ in the hippocampal slice with membrane‐permeable Zn2+ chelators, dithizone, or diethyldithiocarbamic acid (DEDTC) blocked the induction of mossy fiber LTP. The mean amplitudes of EPSCs after tetanus were 194 ± 22% of baseline value in control (n = 5), compared to 108 ± 14% in dithizone (n = 6) and 101 ± 12% in DEDTC (n = 5). The averaged value of LTP, at the associational commisural fiber‐CA3 synapses, was 193 ± 20% in the control (n = 6), compared to 182 ± 21% (n = 6, P > 0.1) in the presence of dithizone. The blockade of mossy fiber LTP by dithizone was reversible after washout. In addition, normal LTP could be induced by tetanus if exogenous Zn2+ was applied immediately following dithizone. Our results indicate that the endogenous Zn2+ is specifically required for LTP induction at the mossy fiber input into CA3 neurons. Synapse 38:187–197, 2000. © 2000 Wiley‐Liss, Inc.