In a recent paper (Ringach, 2007), Dario Ringach presents a novel account of cortical development, addressing a broad range of data on the formation of orientation selectivity and ocular dominance columns in the visual system. The model proposed is based on an abstract (rather than mechanistic) statistical approach to connectivity between retina, LGN, and visual cortex. In Ringach’s model, the probability of establishing connections between regions is primarily dependent on a Gaussian function, where the highest probability occurs if the spatial location of receptive fields overlaps completely (given cells of the same signature – ON or OFF). (A similar probability is also computed to determine synaptic efficacy). The resulting statistical characterizing can concisely account for an impressive amount of developmental data, and is part of a broader trend towards statistical approaches to neural development. For instance, a probabilistic Markov model was recently developed to account for the interplay of genes and activity-based mechanisms in normal and genetically-altered stages of early retinocollicular development (Koulakov & Tsigankov, 2004).



Ultimately, however, while a statistical account can help shed new light on some of the fundamental properties of experimental data, it cannot supersede more mechanistic accounts of these phenomena (Koulakov & Chklovskii, 2001), such as those that incorporate precise biophysical mechanisms, including Hebbian learning (Hebb, 1949) and physical constraints (e.g., minimization of wiring length; Koulakov & Chklovskii, 2001). An examination of some of the limits of Ringach’s statistical account helps to explain why. For example, Ringach’s account leaves open questions such as why initial conditions seeding the maps cannot be fully reversed or disrupted by later activity-dependent influences. Likewise important findings in both retinocollicular and retinogeniculate development such as developmental deficiencies associated with genetic (i.e., knockout and transgenic) manipulations (for a review, see McLaughlin & O'Leary, 2005), as well as manipulations that disrupt spontaneous retinal activity during a brief critical period of development (e.g., McLaughlin et al., 2003; Chandrasekaran et al., 2005; Mrsic-Flogel et al., 2005). Map disruptions caused by knockout manipulations or removal of spontaneous retinal activity (for a review, see McLaughlin & O'Leary, 2005) are not directly addressed by the work of Ringach and likely reside outside the scope of a purely statistical approach.



The lack of an integrated theoretical framework for understanding these findings is a tell-tale sign that many fundamental aspects of both molecular and activity-based influences are still poorly understood. Investigating the mechanisms behind neural development will require a re-examination of several factors that are too often overlooked in the bird’s eye view provided by statistical modeling. For instance, repulsive cell-cell signalling cues responsible for intrinsic axonal competition is a mechanism that is still not clearly understood (Honda, 2003), and many accounts, including that of Ringach, simply assume that axons “swap” position when required to fit a particular statistical goal. By doing so, most extant models have made little attempts to capture a wealth of evidence on the role of neural activity in controlling and shaping the axonal branches responsible for establishing contact points between regions (Uesaka et al., 2005).



Going further, detailed models are also required to address the particular interplay of activity-based and activity-independent mechanisms; while most current models assume that activity-based development is initiated during a phase of development where activity-independent mechanisms no longer play a role, recent evidence suggests just the opposite: the genetically-expressed factors continue to exert an influence well beyond the initial stages of activity-independent development (Cline, 2003). Advances in our understanding of cortical map formation may therefore depend on models that account for the continued influence of molecular guidance cues even after the introduction of neural activity. Overall, mechanistic models may be better suited at explaining how certain basic principles such as Hebbian learning lead to dynamic changes over time, i.e., changes in connectivity and synaptic efficacy, as well as the time-course of influence of molecular versus activity-based processes.



More broadly, although it may appear at first sight that a purely statistical view of visual development is in competition with other alternatives such as Hebbian-based correlation approaches, it is perhaps more likely that they represent two sides of the same coin; while one offers a detailed description of what visual development looks like, the other promises an explanation of how fundamental mechanisms involved in development can account for the final layout of orientation, retinotopic, and ocular dominance maps.



Chandrasekaran A, Plaas D, Gonzalez E, Crair M (2005) Evidence for an instructive role of retinal activity in retinotopic map refinement in the superior colliculus of the mouse. Journal of Neuroscience 25:6929-6938. [http://www.jneurosci.org/...]



Cline, H. 2003. Sperry and Hebb: Oil and Vineagar? Trends in Neurosciences, 26, 655-661.



Goodhill G, Xu J (2005) The development of retinotectal maps: A review of models based on molecular gradients. Network: Computation in Neural Systems 16:5-34.



Hebb D (1949) The Organization of Behavior. New York: Wiley.



Koulakov, AA, Tsigankov, DN. 2004. A stochastic model for retinocollicular map development. BMC Neurosci, 5:30. [http://www.pubmedcentral....]



McLaughlin T, O'Leary D (2005) Molecular gradients and development of retinotopic

maps. Annual Review of Neuroscience 28:327-355.

McLaughlin T, Torborg C, Feller M, O'Leary DDM (2003) Retinotopic map refinement requires spontaneous retinal waves during a brief critical period of development. Neuron 40:1147-1160.



Mrsic-Flogel T, Hofer S, Creutzfeldt C, Cloez-Tayarani I, Changeux J, Bonhoeffer T, Hubener M (2005) Altered map of visual space in the superior colliculus of mice lacking early retinal waves. Journal of Neuroscience 25:6921-6928. [http://www.jneurosci.org/...]



Ringach, 2007. On the origin of the functional architecture of the cortex. PLoS ONE, 2(2), e251.



Uesaka N, Hirai, S., Maruyama, T., Ruthazer, E.S., Yamamoto, N. 2005. Activity dependence of cortical axon branch formation: A morphological and electrophysiological study using organotypic slice cultures. J Neurosci, 25, 1-9. [http://www.jneurosci.org/...]