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

✍ Scribed by You-Ming Lu; Franco A. Taverna; Rita Tu; Cameron A. Ackerley; Yu-Tian Wang; John Roder

Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
369 KB
Volume
38
Category
Article
ISSN
0887-4476

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✦ Synopsis

The functional role of the abundant Zn 2ϩ found in some hippocampal synapses has been an enigma. We show here, using N-[6-methoxy-8-quinolyl]-P-toluenesulfonamide (TSQ) staining, that chelatable-Zn 2ϩ can be removed from hippocampal synaptic boutons using dietary depletion or with Zn 2ϩ chelators. A chronic dietary deficiency of bouton Zn 2ϩ 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 Ϯ 28% of baseline value in control (mean Ϯ SEM, n ϭ 10), and 118 Ϯ 12% in Zn 2ϩ -deficient rats (mean Ϯ SEM, n ϭ 12, P Ͻ 0.01). In the deficient rats with Zn 2ϩ supplements, mossy fiber LTP returned to normal levels. The acute depletion of bouton Zn 2ϩ in the hippocampal slice with membrane-permeable Zn 2ϩ chelators, dithizone, or diethyldithiocarbamic acid (DEDTC) blocked the induction of mossy fiber LTP. The mean amplitudes of EPSCs after tetanus were 194 Ϯ 22% of baseline value in control (n ϭ 5), compared to 108 Ϯ 14% in dithizone (n ϭ 6) and 101 Ϯ 12% in DEDTC (n ϭ 5). The averaged value of LTP, at the associational commisural fiber-CA3 synapses, was 193 Ϯ 20% in the control (n ϭ 6), compared to 182 Ϯ 21% (n ϭ 6, P Ͼ 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 Zn 2ϩ was applied immediately following dithizone. Our results indicate that the endogenous Zn 2ϩ is specifically required for LTP induction at the mossy fiber input into CA3 neurons.

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