Activation of nicotinic acetylcholine receptors patterns network activity in the rodent hippocampus

1. Intracellular and extracellular recordings front area CA3 of rat and mou se hippocampal slices revealed two distinct modes of synchronous network ac tivity in response to continuous application of muscarinic acetylcholine re ceptor (mAChR) agonists. At low concentrations (e.g. 0.1-1 mu M oxotremorin e-M), 'burst-mode' activity comprised regular individual AMPA receptor-medi ated depolarizing events, each generating several action potentials. At hig her concentrations (5-50 mu M), 'theta-mode' prevailed in which ordered clu sters of depolarizing theta-frequency oscillations occurred. 2. Whilst theta-mode activity was abolished by the mAChR antagonist atropin e (5 mu M), the nicotinic acetylcholine receptor (nAChR) antagonists tubocu rarine (100 mu m), mecamylamine (100-500 mu M) and dihydro-beta-erythroidin e (250 mu M) converted this mode of activity to burst-mode. 3. Likewise, disruption of synaptically available ACh using inhibitors of c holine uptake (hemicholinium-3; 20-50 mu M) or vesicular ACh transport (ves amicol; 50 mu M) converted theta-mode into burst-mode activity. 4. Hippocampal slices prepared 2-3 weeks after transection of the primary c holinergic efferent pathway from the medial septum exhibited reduced vesicu lar ACh transporter immunoreactivity but still supported nAChR-dependent th eta-mode activity suggesting that ACh released from this pathway was not cr itical for the activation of these receptors. 5. In summary ACh-mediated activation of nAChRs tailors the pattern of netw ork activity into theta-frequency depolarizing episodes as opposed to synch ronized individual events at much lower frequencies.