We also observed increased bursting of complex spikes in the HCN1 knockout mice. Complex bursts are known to be important for information coding in hippocampus (Lisman, 1997) and bursts with shorter intervals are known to elicit LTP (Larson et al., 1986) and have an important role in synaptic plasticity (Thomas et al., 1998). We see a significant increase in complex bursting of CA1 place cells whereas CA3 place cells show
only a small, statistically insignificant increase in bursting, probably due to their low level of HCN1 expression. Complex bursts are thought to depend on the firing of dendritic Ca2+ spikes (Kamondi et al., 1998a). The increased CA1 bursting is consistent with the observation that the dendritic spikes are enhanced in CA1 neurons (Tsay et al., 2007). HCN1 channels are required for the large selleck products Ih in the stellate neurons of layer II of EC (Garden et al., 2008) where they regulate low-frequency membrane potential oscillations (Giocomo and Hasselmo, 2009). Forskolin order Therefore, one cannot rule out the possibility that the bursting properties of the hippocampal neurons could be driven by grid cell inputs. The results on the HCN1 knockout mice thus reveal
a series of phenotypic changes in learning and memory, on the one hand, and place cell properties on the other. Comparison of changes in CA1 and CA3 place cells indicate that these alterations are likely to reflect both changes in the entorhinal cortex grid cell inputs to these neurons as well as, in the case of CA1, a direct influence of HCN1 intrinsic to the place cell. Taken together with the results of Giocomo et al. (2011) on how HCN1 deletion alters grid cell properties, these results provide strong evidence that the firing properties of grid cells are important determinants of the properties of the downstream hippocampal place cells. Moreover, these properties are likely to contribute to the action of HCN1 to constrain spatial learning and memory. Forebrain restricted HCN1 KO mice (HCN1f/f,cre) and control littermates (HCN1f/f)
in a hybrid 50:50% C57BL/6J:129SVEV background were bred and raised in the New York State Psychiatric Institute animal care others facilities as described (Nolan et al., 2004 and Nolan et al., 2003). Mice were studied between 3 and 6 months of age and weighed about 26–37 g at the time of electrode implantation surgery. The littermates were housed in groups of not more than five per cage. Following surgery, all mice were individually housed under 12 hr light/dark cycle and provided with food and water ad libitum. All breeding and housing procedures conformed to National Institute of Health (NIH) standards using protocols approved by the Institutional Animal Care and Use Committee (IACUC).