The aim of this investigation was to examine the mechanisms implicated in the processes of learning and memory in the rodent hippocampus using electrophysiological recording techniques to monitor CA1 pyramidal cell activity. In the presence of ionotropic glutamate and g-aminobutyric acid (GABA) receptor antagonists, stimulation of the septohippocampal cholingeric afferents, in stratum oriens, produced a slow excitatory postsynaptic potential (EPSP). Subsequent pharmacological classification established that this response was mediated by activation of muscarine acetylcholine receptors (mAChR) and as such this response was termed an EPSP_M. Specific blockers of voltage-gated Ca²⁺ channels, w-conotoxin GVIA and w-agatoxin IVA, revealed that the release of ACh necessary to evoke the EPSP_M was mediated by activation of both N- and P/Q-type Ca²⁺ channels. Blockade of presynaptic 4-AP-senstivie K⁺ channels further enhanced the release of ACh. A previous report had shown that mAChR-mediated synaptic transmission could be modulated by adenosine A₁ receptor activation but had not examined the precise cellular mechanisms underlying this effect. Investigations have revealed that the activation of A₁ receptors inhibited the EPSP_M irrespective of the Ca²⁺ channel supporting this response and that there maybe a partial involvement of 4-AP sensitive K⁺ channels. As adenosine A₁ receptors are known to act via the G-protein, G_i/o, we also investigated the involvement of cAMP in the inhibition of the EPSP_M. It was demonstrated that forskolin stimulated increases in cAMP partially occluded and 8-Br cAMP application fully occluded the adenosine A₁ receptor-mediated inhibition of the EPSP_M. Most synapses are under the regulation of a variety of GPCRs. In this respect we also demonstrated that opioid receptor agonists could modulate the EPSP_M. Interestingly, it was found that opioid agonists acting at a presynaptic m-opioid receptor caused an enhancement of the EPSP_M although the mechanism of how this is achieved is unclear.