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.

Keywords:

• 192IgG-saporin
• acetylcholine
• long-term potentiation
• hippocampus
• septum
• fEPSP

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

Current experiments were approved by the Ethical Committee of the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences (No. 4, 2017). This study was performed in accordance with the ethical principles stated in the European directive (2010/63/EU) and the principles of the Guide for the Care and Use of Laboratory Animals.

Availability of data and materials

All data that was made or analyzed in this study are included in this manuscript. All of the raw data are stored in the Laboratory of the Neurophysiology of learning, Institute of Higher Nervous Activity and Neurophysiology Russian Academy of science. All data used in the current paper are available on reasonable request.

Authors’ contributions

AB and VM designed the study. YD managed the data collection. YD and AB made the statistical analysis. YD wrote the first draft of the manuscript. All authors read, corrected and approved the final version of the manuscript.

Additional information

Funding

The work was supported the Russian Science Foundation under Grant (no. 16-15-10403П).