, 2012). Together, these technical advances in optical imaging, electrophysiology, molecular genetics, and behavior have helped shed new light

on the functional role of L2/3 in awake behaving mice, which forms the focus of this Review. The vast majority of neocortical neurons (∼80%) are excitatory, releasing glutamate onto their synaptically UMI-77 ic50 connected targets. The types of excitatory neurons in sensory neocortex vary according to laminar position of the cell body (Figure 1A). L1 only contains GABAergic neuronal somata and, of course, many glutamatergic and GABAergic axons, dendrites, and synapses. In the mouse, L1 is ∼125 μm thick, varying across cortical regions. The excitatory neurons in the superficial neocortical layers, L2/3, are densely packed pyramidal neurons with prominent vertically aligned apical dendrites. At the border between L1 and L2, many of the excitatory neurons are modified pyramidal neurons, which can have near horizontal or very short apical dendrites. Excitatory L2/3 neurons locally innervate L2/3 and L5, and have long-range axonal projections that project to distant cortical areas. In mouse Kinase Inhibitor Library neocortex, L2 and L3 have a combined thickness of ∼300 μm. Most two-photon imaging studies have been performed within the upper ∼400 μm of the neocortex

spanning from L1 to L3, since imaging deeper in the brain is technically more challenging (Mittmann et al., 2011). Excitatory neurons in L4 are typically dominated by spiny stellate neurons with small somata and dendrites confined to L4. Excitatory L4 neurons only have local axonal arborizations, prominently innervating excitatory neurons within L4, as well as in all other cortical layers of the same column (Figure 1A) (Lefort et al., 2009). The deep L5 excitatory pyramidal neurons have larger cell bodies and prominent apical dendrites ascending to the superficial layers. The

excitatory L5 neurons receive excitatory input from all other cortical layers and have long-range axonal projections to cortical and subcortical brain regions. Layer 6 contains Exoribonuclease a large diversity of excitatory cell types including pyramidal neurons with vertically aligned apical dendrites reaching L4 and inverted pyramidal neurons. Excitatory neurons in L6 send long-range axonal projections across cortical areas and also innervate the thalamus. In the studies that have directly compared the AP firing rates across different layers, there is growing agreement that L2/3 pyramidal neurons have significantly lower firing rates than excitatory neurons in L4 and L5. Sparse AP firing in the superficial layers was already noted in early whole-cell recording studies carried out under anesthesia (Moore and Nelson, 1998; Zhu and Connors, 1999; Brecht et al., 2003).