, 2009). Both L2 and L3 excitatory neurons are strongly innervated by L4 neurons, which will also learn more contribute to the sensory responses ( Feldmeyer et al., 2002; Lefort et al., 2009) ( Figure 2D). In addition, L2 neurons also receive a potentially important excitatory input from L5A neurons, whereas L5B neurons make fewer connections with excitatory neurons in L2/3
( Figure 2D) ( Lefort et al., 2009). Although these “noncanonical” synaptic pathways from deeper to superficial cortical layers occur at relatively low probabilities of finding connected pairs of neurons, they may be functionally important since L5 pyramidal neurons fire APs at higher rates than L2/3 excitatory neurons, as discussed above. In future studies, it would
appear to be important selleck kinase inhibitor and interesting to carefully probe for further functional differences between L2 and L3. It is also conceivable that future molecular labels will be able to subdivide L1, L2, and L3 into many further sublaminae. So far we have considered the excitatory glutamatergic neurons, which make up ∼80% of the neocortical neuronal population. The remainder of neocortical neurons are inhibitory GABAergic neurons, which for the most part only have local axonal arborizations and are therefore often termed “interneurons.” The GABAergic neurons show a striking diversity of morphological, molecular, and electrophysiological features (Ascoli et al., 2008). Recently, it has been suggested that the neocortical GABAergic neurons
can be divided into three largely nonoverlapping groups defined by molecular markers (Lee et al., 2010). In L2/3, the largest group of neurons, accounting for ∼50% of the GABAergic population, expresses the ionotropic serotonin receptor 5-HT3AR and nicotinic acetylcholine receptors but does not express parvalbumin or somatostatin. These 5HT3AR-expressing neurons have broad AP waveforms with adapting firing patterns, corresponding to the large class of non-fast-spiking GABAergic neurons reported in GAD67-GFP mice (Gentet et al., 2010, 2012; Avermann et al., 2012; Suzuki and Bekkers, 2010). Here, for simplicity, we will refer to these as 5HT3AR cells, which are likely to include at least two different subclasses of GABAergic neurons, one being the neurogliaform cells, which predominantly signal via volume transmission (Oláh et al., 2009), and the other type being VIP-expressing bipolar Cell neurons, which might preferentially inhibit other GABAergic neurons (Acsády et al., 1996; Dalezios et al., 2002; Staiger et al., 2004). The 5HT3AR neurons can be visualized in BAC transgenic mice expressing GFP under the control of the 5HT3AR promoter (Lee et al., 2010) and the subset of VIP-expressing neurons can be examined using VIP-Cre mice (Taniguchi et al., 2011). The second largest group of L2/3 GABAergic neurons is defined through expression of the calcium-binding protein parvalbumin (PV). These PV cells account for ∼30% of the L2/3 inhibitory neurons.