Metabotropic receptor stimulation coupled to weak tetanus leads to long-term potentiation and a rapid elevation of cytosolic protein kinase C activity.

We have previously shown that short-term potentiation (STP) inducing weak tetanus induces long-term potentiation (LTP) when it is coupled with activation of metabotropic glutamate (mGlu) receptors by trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) in rat CA1 slices. In the present study, we examined if this conversion of STP to LTP involves activation of protein kinase C (PKC). Two minutes but not 30 min after coupling, there was a significant increase in the activator-dependent PKC activity in the cytosolic fraction. STP induction or t-ACPD application did not change PKC activity. There was no activity increase in the membrane fraction. STP was also induced by a co-application of gamma-amino-3-hydroxy-5-methyllisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA). Coupling this STP with t-ACPD, however, did not result in an LTP or PKC activity increase, indicating a requirement for synaptic activity. A rapid and transient (< 5 min) increase in cytosolic PKC activity was also seen after the induction of LTP by stronger tetanic stimulation. No LTP tested in the present study was accompanied by activator-independent, persistent increases in PKC activity. STP induction depends on NMDA receptor activation, and the activation of mGlu receptors results in the production of intracellular second messengers. Our results therefore indicate that these separate components may add and bring about PKC activation and LTP.

Enhancement of extracellular protein concentrations during long-term potentiation in the rat hippocampal slice.

The possibility that the enhancement of extracellular protein concentrations during long-term potentiation is related to the maintenance of long-term potentiation was examined in area CA1 of rat hippocampal slices. First, we found that during the 3 h after induction, long-term potentiation maintenance was correlated with a persistent enhancement of extracellular protein concentrations. Second, when the protein synthesis inhibitor cycloheximide was applied 10-15 min before long-term potentiation induction, the drug blocked both the maintenance of long-term potentiation and the elevation of extracellular protein concentrations. These results suggest that the elevation of extracellular protein concentrations requires new protein synthesis. The results further indicate that the newly synthesized proteins may play a role in the maintenance of long-term potentiation.

Developmental study of [3H]TCP and [3H]glycine binding sites in the rat hippocampus.

The postnatal development of [3H]thienylphencyclidine ([3H]TCP) sites in rat hippocampus has been studied autoradiographically and with membrane preparations. [3H]TCP binding increased progressively from birth to adulthood; this is due to a change in the maximal number of sites (Bmax) but not in the affinity (Kd). A different developmental pattern was found for strychnine-insensitive [3H]glycine binding which also increased after birth, but reached adult levels earlier than [3H]TCP binding. The ontogenesis of TCP or glycine sites also differed from that previously described for N-methyl-D-aspartate (NMDA) sites in the hippocampus. In neonatal, as in adult hippocampus, [3H]TCP binding was enhanced by NMDA or glycine and reduced by Mg2+. We suggest that TCP sites are functionally coupled to the NMDA receptor-ion channel complex in developing as in mature hippocampus, but that there are developmental changes in the receptor channel complex.