EFFECT OF TWO NEW TRIPEPTIDES ON THE HIPPOCAMPUS IN RATS

Experiments on hippocampal slices in rats showed that, in contrast to piracetam (100 µM to 10 mM), two new tripeptides, i.e. H-asparagil-glutamyl-proline-OH and H-asparagil-glutamyl-arginin-OH (concentrations 500 µM, 1 and 2.5 mM respectively), strengthened the orthodrome population responses in field СА1. In all three concentrations the effect of H-asparagil-glutamyl-proline-OH was stronger than of the other tripeptide. That is both tripeptides facilitate synaptic transmission within the Schaffer collaterals-pyramidal neurons system in hippocumpal field CA1. Similarly to piracetam (100 µM, within 15 minutes) these tripeptides supported short-term potentiation of the hippocampal synaptic transfer by N-methyl-D-aspartate (NMDA). Specific NMDA-receptors antagonist D-AP5 cancelled the NMDA effect fully which infers that the observed effect is achieved through activation of NMDA-receptors. Effect from H-asparagil-glutamyl-proline-OH excelled equally piracetam and H-asparagil-glutamyl-arginin-OH; H-asparagil-glutamyl-arginin-OH excelled piracetam only.

Activity-dependent differences in function between proximal and distal Schaffer collaterals

Axon conduction fidelity is important for signal transmission and has been studied in various axons, including the Schaffer collateral axons of the hippocampus. Previously, we reported that high-frequency stimulation (HFS) depresses Schaffer collateral excitability when assessed by whole-cell recordings from CA3 pyramidal cells but induces biphasic excitability changes (increase followed by decrease) in extracellular recordings of CA1 fiber volleys. Here, we examined responses from proximal (whole-cell or field-potential recordings from CA3 pyramidal cell somata) and distal (field-potential recordings from CA1 stratum radiatum) portions of the Schaffer collaterals during HFS and burst stimulation in hippocampal slices. Whole-cell and dual-field-potential recordings using 10–100-Hz HFS revealed frequency-dependent changes like those previously described, with higher frequencies producing more drastic changes. Dual-field-potential recordings revealed substantial differences in the response to HFS between proximal and distal regions of the Schaffer collaterals, with proximal axons depressing more strongly and only distal axons showing an initial excitability increase. Because CA3 pyramidal neurons normally fire in short bursts rather than long high-frequency trains, we repeated the dual recordings using 100–1,000-ms interval burst stimulation. Burst stimulation produced changes similar to those during HFS, with shorter intervals causing more drastic changes and substantial differences observed between proximal and distal axons. We suggest that functional differences between proximal and distal Schaffer collaterals may allow selective filtering of nonphysiological activity while maximizing successful conduction of physiological activity throughout an extensive axonal arbor.