They showed that higher levels in the hierarchy

learn to predict visual features that extend across many CRFs in the lower levels (e.g., tree trunks or horizons). Hence, higher visual areas come to predict that visual stimuli will span the receptive fields of cells in lower visual areas. In this setting, a stimulus that is confined to a CRF would elicit a strong prediction error signal (because it cannot be predicted). This provides a simple explanation for the findings of Hupé et al. (1998) and Bullier et al. (1996): when feedback connections are deactivated, there are no top-down predictions to explain responses in lower areas, leading to a disinhibition of responses in earlier areas when—and only when—stimuli can be predicted over multiple CRFs. selleckchem How might the inhibitory effect of feedback connections be mediated? The established view is that extrinsic corticocortical connections are exclusively excitatory (using glutamate as their excitatory neurotransmitter), although recent evidence suggests that inhibitory extrinsic connections exist and may play an important role in synchronizing distant regions (Melzer et al., 2012). However, one important

route by which feedback connections could mediate selective inhibition is via their termination in L1 (Anderson and Martin, 2006; Shipp, 2007): layer 1 is sometimes referred to as acellular due to its pale appearance with Nissl staining (the classical method

for separating layers that selectively labels cell bodies). Indeed, a recent study concluded that L1 contains less than 0.5% of all cells in a Y-27632 clinical trial cortical column (Meyer et al., 2011). These L1 cells are almost all inhibitory and interconnect strongly with each other via electrical isothipendyl connections and chemical synapses (Chu et al., 2003). Simultaneous whole-cell patch-clamp recordings show that they provide strong monosynaptic inhibition to L2/3 pyramidal cells, whose apical dendrites project into L1 (Chu et al., 2003; Wozny and Williams, 2011). This means that L1 inhibitory cells are in a prime position to mediate inhibitory effects of extrinsic feedback. The laminar location highlighted by these studies—the bottom of L1 and the top of L2/3—has recently been shown to be a “hotspot” of inhibition in the column (Meyer et al., 2011). Indeed, a study of rat barrel cortex, which stimulated (and inactivated) L1, showed that it exerts a powerful inhibitory effect on whisker-evoked responses (Shlosberg et al., 2006). These studies suggest that corticocortical feedback connections could deliver strong inhibition, if they were to recruit the inhibitory potential of L1. In terms of the excitatory and modulatory effect of feedback connections, predictive input from higher cortical areas might have an important impact via the distal dendrites of pyramidal neurons (Larkum et al., 2009).