Evoked slow muscarinic acetylcholinergic synaptic potentials in rat hippocampal interneurons

The hippocampus receives an extensive cholinergic input from the medial septal nucleus that ramifies throughout all layers and plays a pivotal modulatory role in cognitive function. Although the pharmacological effects of exogenous application of cholinergic agonists have been extensively studied in hippocampal neurons, much less is known about the effects of synaptically released acetylcholine (ACh). In this respect, most studies have focused on the cholinergic afferent input to pyramidal neurons that produces a characteristically slow depolarizing synaptic response mediated by activation of muscarinic ACh receptors (mAChRs). Here we report that cholinergic afferent stimulation also elicits atropine-sensitive synaptic potentials in hippocampal CA1 interneurons but, in contrast to synaptic responses in pyramidal neurons, these are highly diverse in waveform, although can still be classified into five distinct subtypes. The most common response type (i) 64% of cells) consisted of a slow sustained membrane potential depolarization. The other 36% of responses could be subdivided into responses comprising of (ii) a biphasic membrane potential change in which an initial slow hyperpolarization subsequently transforms into a slow depolarization (20%), (iii) a pure, slow hyperpolarization (13%), and (iv) an oscillatory response persisting for several seconds (2%). Interestingly, there were also interneurons totally insensitive to both synaptic and pharmacological cholinergic challenge. Morphological investigation of recorded cells revealed no obvious correlation between responsiveness to cholinergic afferent stimulation and dendritic and axonal arborization. The current study suggests that synaptic release of ACh results in a complex and differential mAChR-mediated modulation of cellular excitability within the hippocampal interneuron population.