Indeed, it has recently been suggested that interneurons might assist in the organization of pyramidal cell assemblies during learning (Assisi et al., 2011; Buzsáki, 2010). For instance, the abrupt change of interneuron firing rates observed while the animal is exposed to a novel environment could promote the formation of new maps and the associated reorganization of pyramidal assemblies (Frank et al., 2004; Nitz and McNaughton, 2004; Wilson and McNaughton, 1993). If interneurons have a role in shaping pyramidal cell assemblies, it is possible that spatial learning and the

associated formation of new pyramidal assemblies may be accompanied by alterations in interneuron circuitry as well. One possible circuit change may occur on local pyramidal inputs targeting

MDV3100 interneurons, which itself could contribute to the interneuron firing rate changes during spatial learning. Indeed, glutamatergic synapses targeting GABAergic interneurons in the hippocampus are modifiable in an activity-dependent manner (Alle et al., 2001; Lamsa et al., 2005, 2007; Perez et al., 2001). Given that a single presynaptic pyramidal cell can reliably excite its postsynaptic interneurons in the hippocampus, the modification of pyramidal cell-interneuron connections can exert wide-ranging impact on circuit function (Csicsvari et al., 1998; Fujisawa et al., 2008; Gulyás et al., 1993; Marshall et al., 2002; Maurer et al., learn more 2006; Miles, 1990). In this study, we examined whether old and newly established network assemblies flicker to test the hypothesis that hippocampal map competition occurs

during spatial learning. In addition, we investigated the contribution of inhibitory circuits by testing the hypothesis that the formation of behaviorally-relevant pyramidal cell assemblies involves the modification of inhibitory microcircuits. We found that the flickering of old and new maps takes place during spatial learning. Surprisingly, many interneurons reorganized their firing patterns during learning, unless forming dynamic associations to the new assemblies in relation to the assembly flickering. Moreover, by measuring spike transmission probability between monosynaptic pyramidal cell-interneuron pairs, we assessed changes of local excitatory connections onto these interneurons. We found that pyramidal cell connections to interneurons exhibited map-specific changes that were developed during learning, which in turn can explain the newly formed associations between interneuron firing and pyramidal assemblies. To explore how interneurons change their coupling strength to pyramidal cell assemblies during spatial learning, hippocampus circuit activity from the CA1 pyramidal cell layer was recorded using multichannel extracellular techniques in rats performing a spatial learning task on a cheeseboard maze (see Figure S1 available online; Experimental Procedures; Dupret et al., 2010).