Rat neocortical slice preparation for electrophysiological and pharmacological studies.

A procedure for the preparation and maintenance of rat neocortical slices for in vitro electrophysiological and pharmacological studies is described. Application of L-glutamate increased the spontaneous firing rate of the cells in these slices. Acetylcholine (ACh) slightly elevated the firing in some cells, while showing no effect on others. The agent, however, produced a prolonged facilitation of the effects of glutamate. N-ethyl maleimide (NEM), a sulphydryl reagent, did not alter the firing rate when applied by itself or along with ACh, but it potentiated the firing rate when administered along with glutamate. It is possible that NEM either interfered with glutamate uptake or altered the tissue responsiveness to the amino acid. The present results do not distinguish between these two possibilities.

Verapamil counteracts depression but not long-lasting potentiation of the hippocampal population spike.

In transversely sectioned rat hippocampal slices, population spikes and population "EPSPs" were recorded from CA1 neurones in response to the stimulation of Schaffer collateral and commissural inputs. High frequency tetanic stimulation (400 Hz, 200 pulses) of an input induced LLP of the homosynaptic response without significantly changing the heterosynaptic response. This LLP was not interrupted by either a 400 Hz tetanus given to the heterosynaptic input or by verapamil (0.33 microM) which blocks Ca++ channels, but not transmitter release. A low frequency tetanus (20 Hz, 200 pulses) given to an input induces co-occurring homosynaptic and heterosynaptic depressions of about 20 min duration. This tetanus could also mask an established LLP in homosynaptic or heterosynaptic pathway. Verapamil counteracts homo- and heterosynaptic depressions. The population spike as well as the population "EPSP" were depressed following iontophoretic application of Ca++ (2-100 nA) at the CA1 cell body area. These results indicate that homosynaptic and heterosynaptic depressions are at least partly due to an accumulation of Ca++ into CA1 neurones. An established LLP is not interrupted by LLP of another input. Homo- and heterosynaptic depressions mask, but not reverse, LLP.

Verapamil counteracts the masking of long-lasting potentiation of hippocampal population spike produced by 2-amino-5-phosphonovalerate.

In transversely sectioned rat hippocampal slices the effects of 2-amino-5-phosphonovalerate (APV), presumably a selective N-methyl-DL-aspartate antagonist, were examined on the development of long-lasting potentiation (LLP) of the CA1 population spike produced by Schaffer collateral tetanization (100 Hz, 1 s). APF (100 nA, 5 min), when applied 150-200 micron away from the CA1 cell bodies (apical dendritic area), had no significant effect if the population spike was evoked at 0.1 Hz, but produced a depression of the population spike if a 100 Hz tetanus was given during its iontophoresis. This depressant effect of APV was counteracted by verapamil (0.33 microM, 3 min) and LLP induced by the 100 Hz tetanus was unmasked. It is suggested that APV does not antagonize LLP, but only masks it by allowing CA++ influx into CA1 neurones that induces a depression. The results also raise doubts as to the selectivity of APV as an amino acid antagonist.