Thus, Bafilomycin A1 molecular weight CA3PC dendrites may efficiently amplify less coherent (but still coincident) synaptic inputs, such as those provided by activity of a memory-coding ensemble structured by theta-gamma oscillation during exploratory behavior. NMDA spikes have a special relationship with burst firing in that bursting input

is a particularly effective stimulus and the spikes themselves enhance bursting output (Polsky et al., 2009). These properties fit with the well-known bursting properties of CA3PCs (Ranck, 1973, Buckmaster and Amaral, 2001 and Mizuseki et al., 2012). Our results are in accordance with the recent report of Kim et al. (2012) that demonstrated that thick CA3PC dendrites can actively generate INCB018424 price local Na+ spikes upon dendritic current injection. In contrast to that study, we stimulated synaptic inputs by two-photon glutamate uncaging in thin dendrites of CA3PCs. While we also detected local dendritic Na+ spikes, we found that Na+ spikes were relatively weak as measured at the soma (especially in the apical arbor) and that supralinearity of integration was rather provided by

NMDARs, a mechanism that could not be studied by the direct current injection used by Kim et al. (2012). Although favoring the initiation of dendritic spikes, the morphological structure of CA3PCs (frequent branching of the apical trunk to several thinner trunks) may lead to strong attenuation of fast Na+ spikes as they propagate to the soma, while slower NMDA spikes should be less affected. Modifiable dendritic K+ currents have been widely implicated in the regulation of synaptic plasticity and dendritic function (Shah et al., 2010). The A-type K+ current received much interest for promoting localized alterations in dendritic function (Frick et al., 2004 and Losonczy et al., 2008), while less attention has been focused on the role of other K+ channels. GIRK channels are activated by various Gi-protein-coupled receptors (Lüscher and Slesinger, 2010), are abundant in dendrites and spines of CA3PCs in Rolziracetam tight association with GABABRs (Gähwiler and Brown, 1985, Sodickson and Bean, 1996,

Lüscher et al., 1997, Koyrakh et al., 2005 and Kulik et al., 2006), and have been recorded in the apical trunk of CA1 and cortical pyramidal neurons (Chen and Johnston, 2005, Takigawa and Alzheimer, 1999, Breton and Stuart, 2012 and Palmer et al., 2012). Consistent with the above data, we found robust, though variable, expression of functional GIRK channels in CA3PC basal distal dendrites. Due to the intrinsic voltage dependency of their conductance, dendritic IRK currents may be well positioned to favor nonlinear processing of spatiotemporally clustered synaptic inputs. High IRK conductance at Vrest reduces input resistance and the time and length constants, thereby limiting integration of distributed synaptic inputs.