Modulation of extracellular monoamine transmitter concentrations in the hippocampus after weak and strong tetanization of the perforant path in freely moving rats.

Hippocampal long-term potentiation (LTP) is considered as a cellular model of memory formation. Specific, electrical weak tetanization of distinct afferents such as the medial perforant path results in a short-lasting, protein synthesis-independent early-LTP (up to 4 h) within the dentate gyrus. A stronger tetanization leads to late-LTP (>4 h), which is protein synthesis-dependent and requires heterosynaptic activation during its induction, the latter of which can be provided by afferents from cortical brain regions or subcortical nuclei during memory formation in the behaving animal. In particular, noradrenaline (NA) is required for late-LTP in the dentate gyrus and dopamine for late-LTP in the apical CA1-dendrites. However, little is known about the concentrations and temporal dynamics of such neuromodulators like NA, serotonin (5-HT) and dopamine (DA) during LTP. We now implemented the microdialysis method to study this topic after stimulating the dentate gyrus in more detail. A weak tetanus of the perforant path, which normally leads to early-LTP, transiently but significantly decreased the concentration of NA (3 h) and increased the concentration of 5-HT (about 2 h) and DA (about 1 h) in the hippocampus. A strong tetanus, normally resulting in late-LTP, increased concentrations of NA and DA significantly and long-lasting (for about 5 h), whereas 5-HT concentration was increased with a delay (after about 30 min) and only for a short time (30 min). Thus different stimulation protocols resulted in different release patterns of neuromodulators, that may support discriminative processing of incoming information in the hippocampus.