Both functional and anatomical techniques have been applied to study intrinsic (intracortical) and extrinsic connections.

We will emphasize the insights from recent studies that combine both techniques. The seminal work of Douglas and Martin (1991), in the cat visual system, produced a model of how information flows through the cortical column. Douglas and Martin recorded intracellular potentials from cells in PLX-4720 in vivo primary visual cortex during electrical stimulation of its thalamic afferents. They noted a stereotypical pattern of fast excitation, followed by slower and longer-lasting inhibition. The latency of the ensuing hyperpolarization distinguished responses in supragranular and infragranular layers. Using conductance-based models, they showed that a simple model could reproduce these responses. Their model contained superficial and deep pyramidal cells with a common pool of inhibitory cells. All three neuronal populations received thalamic drive and were fully interconnected. The deep pyramidal cells received relatively weak thalamic drive but strong inhibition (Figure 1). These interconnections allowed the circuit to amplify transient thalamic inputs to generate sustained activity in the cortex, while maintaining a balance between excitation and inhibition, two tasks that

must be solved by any cortical circuit. Their circuit, although based on recordings from cat visual cortex, was also proposed selleck as a basic theme that might be present and replicated, with minor variations, throughout the cortical sheet (Douglas et al., 1989). Subsequent studies have used intracellular recordings and histology to measure spikes (and depolarization)

in pre- and postsynaptic cells, whose cellular morphology can be determined. This approach quantifies both the connection probability—defined as the number of observed connections divided by total number of pairs recorded—and connection strength—defined in terms of postsynaptic responses. Thomson et al. (2002) used these techniques to study layers 2 to 5 (L2 to L5) of the cat and rat visual systems. The most frequently connected cells were located in the same to cortical layer, where the largest interlaminar projections were the “feedforward” connections from L4 to L3 and from L3 to L5. Excitatory reciprocal “feedback” connections were not observed (L3 to L4) or less common (L5 to L3), suggesting that excitation spreads within the column in a feedforward fashion. Feedback connections were typically seen when pyramidal cells in one layer targeted inhibitory cells in another (see Thomson and Bannister, 2003 for a review). While many studies have focused on excitatory connections, a few have examined inhibitory connections. These are more difficult to study, because inhibitory cells are less common than excitatory cells, and because there are at least seven distinct morphological classes (Salin and Bullier, 1995).