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

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.

[A Role of the Wnt Signaling in the Regulation of Brain Function].

The review describes the Writ signaling pathway participation in the embryonic development, such as cell specification, migration and polarity. Recent studies have shown that the Wnt pathway plays one of the key roles in the processes of synaptic plasticity and memory formation. In this review there are evidences of the Wnt cascade involvement in the modulation of synaptic efficacy at both pre- and postsynaptic levels. Here we analyze the role of Wnt ligands in synaptic plasticity and behavior. Finally, we describe that components of Wnt pathways are involved in the development of major neurological and psychiatric disorders, including a neuroprotective role of Wnt proteins in the pathogenesis of Alzheimer's disease.

Administration of nicotinic receptor antagonists during the period of memory consolidation affects passive avoidance learning and modulates synaptic efficiency in the CA1 region in vivo.

We examined whether a non-selective antagonist of nAChRs mecamylamine and selective antagonists of α4ß2-containing nAChRs dihydro-ß-erythroidine (DHßE) and α7-containing nAChRs methyllycaconitine (MLA) affect learning performance and synaptic efficiency in the CA1 area of the hippocampus of freely moving rats during the memory consolidation period. Adult male Wistar rats received mecamylamine (0.5 mg/kg), DHßE (1 mg/kg), MLA (2 mg/kg) or saline immediately after training in a passive avoidance task. Memory retention was examined 24 h after the training. The changes in the latency of the first entry into a dark compartment of a test chamber were chosen as a criterion of learning. The ability of nAChRs antagonists to induce changes in the basal level of focal potentials (fEPSP, field excitatory postsynaptic potential) was estimated before training (baseline), 90 min after the training (consolidation period) and 24 h after the training (retention period). We found that in untrained rats mecamylamine, DHßE and MLA diminished the amplitude of fEPSP within the first 90 min after the injection; similar effect was observed in DHßE- and MLA-treated trained animals. These suppressive effects of DHßE and MLA were associated with memory loss. In contrast, mecamylamine, when applied to trained animals, tended to increase latency to enter the dark chamber and did not influence fEPSP during first 90 min after injection. Thus, the nAChRs antagonists with different selectivity induced different changes in fEPSP and behavior which suggests that nAChRs with different subunit composition are diversely involved in memory consolidation.