Functional specificity can be defined as any form of synaptic specificity that cannot be explained by axonal and dendritic

topography, cell types, or perhaps even gene expression but instead must relate to the physiology of the pre- and postsynaptic cells. A more accurate term might therefore be local functional connectivity or even local epigenetic specificity. The three types of specificity are of course not perfectly delineated; they nonetheless serve as useful abstractions until we have a better understanding of molecular and activity-dependent influences on neuronal connectivity. The LGN is a particularly well-studied example in which topographic specificity plays some role, but functional specificity comes to dominate the local wiring diagram. The retinal input to the thalamus is one of the classic models Pictilisib cost for the segregation of inputs into both eye-specific layers and retinotopic maps. But even after topographic segregation Lumacaftor order of axonal arbors is

complete, midway through development, there is further synaptic refinement (Tavazoie and Reid, 2000; Chen and Regehr, 2000). At the end of development, there is a very specific network in which multiple overlapping axons make synaptic contact onto distinct and very specific targets. This was demonstrated in a serial-section EM study (Hamos et al., 1987) that 25 years later remains the clearest anatomical illustration of functional specificity in central circuits. As discussed below, and as elaborated in an extraordinary review of the relationship between connectivity and visual function (Cleland, 1986), the mature wiring diagram between retina and LGN must have a crystalline underlying structure based on the geometric tiling of retinal receptive fields. The relationship between cortical wiring and visual function, however, is far more complicated. The generation of orientation-selective visual responses in the cortex is one of the classic problems in visual neuroscience. Neurons in medroxyprogesterone the visual

thalamus (the LGN) respond relatively indiscriminately to stimuli of different orientations, while their postsynaptic targets in the cortex can be exquisitely selective. In the first of their two models of function and connectivity, Hubel and Wiesel outlined how precise connections between thalamus and cortex could generate the orientation-selective responses of cortical simple cells (Figure 1A). In the most famous figure of the 1962 paper, they proposed that LGN cells whose receptive fields were arranged in a row converge onto a simple cell whose receptive field was elongated with the same orientation (Figure 1A). As it turned out, this class of model could be proven with 20th century electrophysiology. In the 1990s, evidence for this model accumulated (Chapman et al., 1991; Reid and Alonso, 1995; Ferster et al., 1996; Priebe and Ferster, 2012).