, 1994, Feldmeyer and Sakmann, 2000 and Markram et al., 1997). If the goal, however, is to eventually reveal most, or all, connections within a given area, this method is limited given the few connections

that can be tested in one experiment. To circumvent this problem, we designed an optical technique, a modification of one-photon photostimulation (Callaway and Katz, 1993), that reveals synaptic connections in large numbers and can provide a map of most connections to a neuron in a local area, with single-cell resolution (Nikolenko et al., GDC 0068 2007). Using two-photon uncaging of glutamate in brain slices, one can sequentially activate hundreds of potential presynaptic cells, one by one, and quickly test whether they are connected to a given postsynaptic neuron (Nikolenko et al., 2007). We were interested to apply this two-photon mapping technique to inhibitory circuits and determine the functional structure of inhibitory networks in the neocortex. The cortex has numerous types of GABAergic interneurons (Fairen et al., 1984), which play a determinant role in the regulation of the excitability of pyramidal cells (PCs) and the activity of cortical microcircuits,

by controlling different parts of the axo-dendritic arborization of the PCs check details (Somogyi et al., 1998). One can distinguish many subtypes of inhibitory neurons in neocortical circuits morphologically and physiologically (Gupta et al., 2000, Ascoli et al., 2008 and Yuste, 2005). For this study, we focused on dendritic targeting inhibitory cells,

the somatostatin-expressing interneurons (Kawaguchi and Kubota, 1997 and Wang et al., 2004), which represent approximately 30% of the neocortical interneurons in mouse (Gonchar and Burkhalter, 1997). Somatostatin-positive cells are composed of several subtypes, of which Martinotti neurons are the predominant type (Halabisky et al., 2006 and McGarry et al., 2010). They generally, although not always (Gonchar et al., 2002), contact apical and tufted dendrites of PCs (Kawaguchi and Kubota, 1997 and Wang very et al., 2004). Somatostatin-positive interneurons display low-threshold spiking (Kawaguchi, 1995), generating a global dendritic calcium spike (Goldberg et al., 2004), and can fire spontaneously in a pacemaker fashion, in the absence of any synaptic input (LeBon-Jego and Yuste, 2007). Within neuronal circuits, they control local synaptic inputs of PCs (Murayama et al., 2009 and Silberberg and Markram, 2007) and are recruited by network activity (Kapfer et al., 2007), to the point that they can be activated by a single PC (Kozloski et al., 2001), mediating a strong disynaptic inhibition between PCs (Silberberg and Markram, 2007). These specific morphological and physiological properties suggest that somatostatin-positive interneurons implement a specific function in the microcircuit.