Comment on “Disruption in the Inhibitory Architecture of the Cell Minicolumn: Implications for Autism”

Abstract

Narrow neural columns have been suggested to be a neuroanatomical abnormality in autism. A previous hypothetical explanation, an unbalance between excitatory and inhibitory lateral feedback in the neocortex, has been found to be difficult to reconcile with the relatively high comorbidity of autism with epilepsy. Two alternative explanations are discussed, an early low capacity for producing serotonin, documented in autism, and insufficient production of nitric oxide. An early low level of serotonin has in animal experiments caused narrow neural columns. Insufficient nitric oxide is known from neural network theory to cause narrow neural columns.

Using Perceptual Signatures to Define and Dissociate Condition-Specific Neural Etiology: Autism and Fragile X Syndrome as Model Conditions

“…Bertone et al's (2005) demonstration of both enhanced and diminished extraction of spatial information was interpreted as the result of atypical neural connectivity within the primary visual cortex (or V1), and interactions with adjacent early cortices. Among the available neural computational models suggesting hypersensitivity in autism (Cohen 1994;McClelland 2000), they argued that the most biologically plausible type of atypical local connectivity congruent with their results is that of strong or excessive lateral inhibition (Gustafsson 1997a, b;Gustafsson 2004), resulting in the inadequate formation of cortical feature maps consisting of neural columns as feature detectors (presented within the context of Kohonen-type (Kohonen 1995), self-organizing maps). Such atypical lateral connectivity would in theory (1) alter early spatial filtering characteristics in autism (i.e., increase tuning of orientation-selective mechanism in V1) and (2) enhance detection capabilities for luminancedefined information by minimizing the signal strength (i.e., luminance-modulation) needed to perceive a stimulus within noise (the implication of short-range feedback connectivity also discussed in Bertone et al 2005).…”

The Neuropathology of Autism

“…Minicolumns are functional modular arrangements of neurons that span most or all neocortical layers of the brain and serve to organize neurons in a defined space and have similar response properties [105, 106]. They are part of a larger macrocolumnar system which is thought to be important in generalization whereas smaller minicolumns may facilitate discrimination [103, 107]. The smaller peripheral neuropil space of minicolumns in ASD has hypothesized impact GABAergic innervation to the minicolumnar neurons and thus may interfere with signal processing and differentiation [103], but further studies are needed.…”

“…Of interest are Gustafsson's comments that narrower minicolumnar organization in autism may, alternatively, be due to an early low capacity for producing serotonin (5-HT) as described in autism [112, 113] as such alterations in minicolumn structure have been seen in lab animals with lower 5-HT levels. Another alternative hypothesis is due to insufficient nitric oxide, which has been shown from neural network analysis to cause narrower neural columns [107]. More recently, Casanova and colleagues conducted a comprehensive analysis of Nissl-based photo mosaics from a number of cerebral cortical areas in autism [114].…”

The Serotonergic System: Its Role in Pathogenesis and Early Developmental Treatment of Autism

“…In contrast, patients with autism demonstrate -until the age of 5- a reduced capacity for synthesis, which, however, increases to reach and overcome adults’ values by the age of 15 [23]. Therefore, the hyperserotonemia, which probably appears in older patients, does not actually develop before an age when most diagnoses of autism have been already made [45]. …”

“…The very detailed focusing, along with the failure to recognize broader contexts of information are probably some of the functional consequences of narrow minicolumns [10]. A tentative case for the explanation of this narrowing can be made for serotonergic disturbances [45]. …”