Long-term potentiation in the hippocampal CA3 to CA1 synapses may be induced in vivo by activation of septal cholinergic inputs

Abstract

Purpose/aim The role of cholinergic neurotransmission in the hippocampus remains controversial since different studies showed either no influence or its modulatory effect on glutamatergic hippocampal synapses. It remains unclear whether septal cholinergic input can modulate plasticity of synapses formed by CA3 pyramids on CA1 neurons. The aim of the study was to clarify the role of septal input in the development of LTP in this synapse. Materials and methods We recorded in vivo in rats under urethane anesthesia focal excitatory postsynaptic potential (fEPSP) characteristics in CA1 area after stimulation of the ventral hippocampal commissure (VHC), which contains both CA3 axons innervating CA1 neurons and cholinergic axons coming from the medial septum. We performed two series of experiments in which LTP was induced by tetanization of either VHC or medial septal area (MSA). Degeneration of cholinergic neurons in MSA was induced by intraseptal injection of 192IgG-saporin. Results In both experimental series, tetanization induced an increase in fEPSP amplitude which lasted for at least 40 min after tetanic stimulation, although tetanization of VHC induced a larger increase in fEPSP amplitude compared to MSA tetanization. Elimination of septal cholinergic neurons by 192IgG-saporin abolished LTP development in both experimental series. This suppression of LTP in animals with cholinergic deficit was not due to loss of hippocampal neurons. Conclusions Our data suggest that activation of septal cholinergic fibers during tetanization is a critical factor of LTP induction in the hippocampal CA3 to CA1 synapses.