Thus, the output from late-bursting cells is principally determined by mGluR activation, which always

see more leads to enhancement of bursting, while the output from early-bursting cells is regulated by both mGluR, which leads to suppression of bursting on its own, and mAChRs, which lead to enhancement of bursting during coactivation with mGluRs. It remains possible that another condition, not yet discovered, could result in downregulation of bursting in late-bursting cells, thus completing a suite of conditions that lead to bidirectional modulation of both cell types in the intact brain. Our findings could promote a better understanding of the well-established dichotomy regarding the role of acetylcholine in learning and memory. Decades of work have shown that cholinergic input facilitates hippocampal activity during memory encoding and learning but suppresses activity during memory retrieval and recall (Drever et al., 2011; Hasselmo, 1999; Micheau and Marighetto, 2011). Our results provide a potential framework for studying the mechanisms of this biphasic role of acetylcholine, as the two types of cells that process and transmit hippocampal information can be differentially modulated by mAChR activation. Furthermore, as projections to CA1 from the entorhinal cortex are more

sensitive to mGluR-dependent presynaptic inhibition than mAChR-dependent inhibition (Giocomo and Hasselmo, 2007), there may be differential modulation of separate information streams flowing directly to CA1 from entorhinal cortex and indirectly through the selleck trisynaptic circuit of the hippocampus. Recent work in vivo has shown that cells with a higher propensity to burst are more likely to become place cells (Epsztein et al., 2010). On the surface, this would suggest that early-bursting cells are more likely to become place cells. As most of the cells in the CA1 region

are late bursting (Jarsky et al., 2008), however, whatever and as place cells are abundant in this region (Moser et al., 2008; Nakazawa et al., 2004; O’Keefe, 1976), it seems unlikely that late-bursting cells are not place cells. Rather, it is possible that both cell types can become place cells and that modulation of neuronal firing patterns with forms of plasticity similar to those described here may serve to enhance or suppress excitability, thus affecting which neurons are likely to exhibit place fields in a particular environment. Similarly, modulation of bursting could contribute to the formation of nonspatial behavioral contingencies on firing (Pastalkova et al., 2008; Wood et al., 2000). ACSF consisted of 125 mM NaCl, 2.5 mM KCl, 25 mM NaHCO3, 1.25 mM NaH2PO4, 1 mM MgCl2, 2 mM CaCl2, and 25 mM dextrose (Fisher Scientific). The pH of the ACSF was 7.3 and the osmolarity was 305–320 mOsm. ACSF was oxygenated and pH buffered by constant bubbling with a gas mixture of 95% O2/5% CO2.