PCBs reduce long-term potentiation in the CA1 region of rat hippocampus.

Prenatal exposure to polychlorinated biphenyls (PCBs) has been associated with a lower IQ in childhood. We have examined the effects of acute exposure to PCB mixtures and two single congeners on synaptic transmission between Schaffer collaterals and CA1 neurons of the rat hippocampus as well as posttetanic potentiation (PTP), paired pulse facilitation (PPF), and long-term potentiation (LTP). PTP and PPF represent transient increases in transmitter release immediately after stimulation, while LTP is a measure of long-term changes in synaptic plasticity that has been related to learning and memory. LTP, but neither PTP nor PPF, was reduced by Aroclor 1016 in a dose-dependent fashion at concentrations that had little effect on general synaptic transmission. The more highly chlorinated Aroclor 1254 at low concentrations specifically blocked LTP, but at higher concentrations also reduced synaptic transmission. The mono-ortho PCB congener 2,4,4'-trichlorobiphenyl and the coplanar congener 3,3',4,4'-tetrachlorobiphenyl also blocked LTP without effect on PTP or PPF. We conclude that PCBs selectively impair the process of LTP in CA1 neurons of the hippocampus.

Factors in the production of experimental autoimmune myasthenia gravis in acetylcholine receptor immunized rabbits.

The development of experimental autoimmune myasthenia gravis (EAMG) was studied in 10 rabbits which were repeatedly injected with Torpedo acetylcholine receptor (AChR). Serum samples were obtained at various times for determination of complement fixing antibody level, serum complement level and the capacity of serum to inhibit neuromuscular transmission in amphibian muscle (passive transfer inhibiting capacity, PTIC). In seven animals the rise in level of circulating antibody occurred immediately before or in synchrony with the development of EAMG and frequently at such times serum complement rose irregularly. The PTIC was elevated during appearance of EAMG. In some animals a rise in complement fixing antibody level occurred without appearance of EAMG; in two others EAMG appeared without significant rise in antibody level. The data indicate that development of EAMG is associated with the production of antibodies which are capable of depressing neuromuscular transmission by reducing the sensitivity of the postjunctional membranes to acetylcholine. This depression can be potentiated by serum complement. Some but not all of the antibodies produced appear to fix complement when combined with Torpedo AChR. Evidence indicating possible existence of a presynaptic contribution to the development of EAMG is given.

Myasthenia in frogs immunized against cholinergic-receptor protein.

Frogs immunized with cholinergic-receptor protein developed myasthenia in 116--175 days. The muscular weakness was overcome by subcutaneous administration of 20 microgram of neostigmine. Electromyograms showed a decline in action potential amplitude during a 2-Hz train. Nerve stimulation evoked subthreshold end-plate potentials (EPPs) averaging 10.4 +/- 7.4 mV, but at many junctions no EPP was obtained. Miniature EPP amplitude had a modal value of 0.15 mV compared with 0.35 mV for the controls. The corresponding means were 0.24 +/- 0.23 mV and 0.48 +/- 0.23 mV. Microperfusion with edrophonium (5 mg/l) increased the amplitude of EPPs and miniature end-plate potentials (MEPPS). Postjunctional response tested with 20 muM carbamylcholine was 56% of control. Postjunctional response by carbamylcholine iontophoresis gave 19 +/- 22 mV/nC compared with 76 +/- 50 mV/nC for the controls. The data indicate that the neuromuscular transmission deficits in receptor-immunized frogs are mainly postsynaptic in origin, but there may be additional presynaptic contributions. This amphibian model of myasthenia gravis offers many opportunities and advantages in the study of receptor-immunized animals.