Large calcium transients could readily be detected in dendrites and dendritic spines of layer V pyramidal neurons in Thy1-GCaMP2.2c mice and in the somata of layer II/III neurons in Thy1-GCaMP3 transgenic mice. In the CNS, odors are represented as patterns of neural activity encoded by time and space. Previous mapping approaches in the olfactory bulb Autophagy inhibitor have used 2-deoxyglucose staining, intrinsic optical signal imaging, and pH-sensitive exocytosis detection to monitor odor-induced changes in neuronal activity. Such functional mapping strategies can provide temporal and spatial resolution of neuronal activity but to date have primarily reported olfactory nerve presynaptic activity, with little (or no)

contribution from Olaparib price postsynaptic neurons. On the other hand, odor responses imaged by bulk-loaded voltage-sensitive dyes comprise a mixture of both pre- and postsynaptic components and do not show genetic specificity (Friedrich and Korsching, 1998; Spors and Grinvald, 2002). More recently, GCaMP2.0 transgenic mice, driven by a Kv3.1 potassium channel promoter, allowed detection of postsynaptic odor representation within the glomerular cell layer, but responses were relatively weak and did not span a dynamic range of odor concentration or specificity (Fletcher et al., 2009).

In Thy1-GCaMP3 mice, GCaMP3 is expressed strongly in the glomerular and mitral cell layers, and responses to odorants were encoded by distinct sets of glomeruli. Concentration coding involved both graded responses from each activated glomerulus, as well as an increase in the total number of glomeruli that responded. Compared to GCaMP2.0 transgenic mice, baseline expression and odor-induced changes in GCaMP fluorescence was significantly higher in Thy1-GCaMP3 mice.

These findings suggest that the Thy1-GCaMP3 transgenic mouse is an improved Sitaxentan genetic tool to investigate neuronal activity changes within the olfactory system. Although our studies only tested the utility of the Thy1-GCaMP mice in the motor cortex, somatosensory cortex, and the olfactory bulb, GCaMP expression in these mice was widespread ( Figures 1 and 2; Figures S2 and S3), and the strains are likely to be useful for monitoring neuronal activity in many brain areas. Stable expression of GCaMP via transgenic mice will enhance our ability to study how information is processed in both the healthy and diseased brain. Together with the recently generated Cre-inducible GCaMP3 mice ( Zariwala et al., 2012), these tools may provide important insights into disease processes and activity-related pathological changes when combined with animal models of neurological disorders. Furthermore, chronic imaging of various subtypes of neurons with GCaMP will help to pinpoint the important groups of neurons, brain regions, and characteristic abnormalities involved in the onset, progression, and end stages of neurological disorders.