Such experiments will improve our understanding of how IEG expression is related to cells’ physiological properties. The cell-type specificity of TRAP is Protein Tyrosine Kinase inhibitor a limitation for some applications. For instance, we found that, after visual stimulation, GABAergic cells were underrepresented among the TRAPed population (Figure S4). This is consistent

with prior work using Fos immunostaining in cats and rats (Mainardi et al., 2009; Van der Gucht et al., 2002). TRAPing of GABAergic cells is likely to be dependent on the stimulus and brain region, and we observed robust TRAPing of some inhibitory neuron types, such as olfactory bulb granule cells and striatal medium spiny neurons (Figure 2). Thus, much of TRAP’s cell type specificity is derived from the cell-type specificity of IEG expression. Additional factors, such as the displacement of regulatory elements during gene targeting, cell-type differences in the accessibility

of the effector http://www.selleckchem.com/products/Docetaxel(Taxotere).html locus for recombination, and cell-type differences in the regulation and trafficking of CreERT2 could potentially contribute. Nonetheless, we show that most cell types in the brain can be TRAPed with the current version of the method. Future modifications, such as the development of CreERT2 knockin alleles for IEGs that are expressed in different neuronal types and that are sensitive to different features of neuronal activity (Schoenenberger et al., 2009; Worley et al., 1993), could extend the approach to cell types that currently cannot be robustly TRAPed. Another concern is that our CreERT2 knockin alleles are expected to be null for Fos and Arc. We did not observe any abnormalities in ArcTRAP or FosTRAP mice, and we are not aware of any severe phenotypes in previously generated Arc and Fos heterozygous knockout mice ( Johnson et al., 1992; Paylor et al., 1994; Wang et al., 2006; Wang et al., 1992).

However, some subtle phenotypes of Arc or Fos haploinsufficiency have been reported. These include a low penetrance Cell press of increased seizure susceptibility in Arc+/− mice ( Peebles et al., 2010), and, for Fos+/− mice, increased susceptibility to drug-induced neurotoxicity ( Deng et al., 1999) and attenuated morphological changes associated with kindling stimuli in an epilepsy model ( Watanabe et al., 1996). Although these phenotypes are unlikely to affect many TRAP experiments, alternative knockin or transgenic strategies that do not produce null alleles could mitigate such concerns. Given that considerable recombination is induced in many brain areas that process sensory information even under homecage conditions, the use of sensory deprivation is useful for improving TRAP specificity (Figure 2).