Identification of ocular dominance domains in New World owl monkeys by immediate-early gene expression.

Ocular dominance columns (ODCs) have been well studied in the striate cortex (V1) of macaques, as well defined arrays of columnar structure that receive inputs from one eye or the other, whereas ODC expression seems more obscure in some New World primate species. ODCs have been identified by means of eye injections of transneuronal transporters and examination of cytochrome oxidase (CO) activity patterns after monocular enucleation. More recently, live-imaging techniques have been used to reveal ODCs. Here, we used the expression of immediate-early genes (IEGs), protooncogene, c-Fos, and zinc finger protein, Zif268, after monocular inactivation (MI) to identify ODCs in V1 of New World owl monkeys. Because IEG expression is more sensitive to activity changes than CO expression, it is capable of revealing activity maps in all layers throughout V1 and demonstrating brief activity changes within a couple of hours. Using IEGs, we not only revealed apparent ODCs in owl monkeys but also discovered a number of unique features of their ODCs. Distinct from those in macaques, these ODCs sometimes bridged to other columns in layer 4 (Brodmann layer 4C). CO blobs straddled ODC borders in the central visual field, whereas they centered ODC patches in the peripheral visual field. In one case, the ODC pattern continued into V2. Finally, an elevation of IEG expression in layer 4 (4C) was observed along ODC borders after only brief MI. Our data provide insights into the structure and variability of ODCs in primates and revive debate over the functions and development of ODCs.

[A 70-year-old male exhibiting parkinsonism-hyperpyrexia syndrome during levodopa carbidopa intestinal gel (LCIG) treatment and suspected carbidopa allergy due to positive drug-induced lymphocyte stimulation test (DLST)].

A 70-year-old male who has medical history of Parkinson's disease for 26 years admitted to our hospital for trial of levodopa carbidopa intestinal gel (LCIG) therapy because of severe dyskinesia and frequent wearing-off. He developed deterioration when he was treated with one of the levodopa (LD) decacrboxylase inhibitor compounds in the past. Five days after LD had changed into equivalent dose of LD/carbidopa (CD), high fever with hyperCKemia appeared. He was diagnosed as having Parkinsonism-hyperpyrexia syndrome (PHS). Exchange of LD/CD to LD drugs improved the symptoms quickly. Four days after LCIG administration, PHS reappeared. Simultaneously, the patient developed sepsis and disseminated intravascular coagulation (DIC). Thrombocytopenia did not improve after recovery from infection and DIC. Anti-PA IgG and drug-induced lymphocyte stimulation test (DLST) against LCIG showed positive. Exchange of LCIG to LD drugs and intravenous methylprednisolone administration improved the symptoms and thrombocytopenia. CD induced type II and type IV allergy were suspected. This case offers a caution that physicians should be aware of drug allergy in cases of which unexpected symptoms occurred in altering one LD compound to another.

Development and Reorganization of Orientation Representation in the Cat Visual Cortex: Experience-Dependent Synaptic Rewiring in Early Life.

To date, numerous mathematical models have been proposed on the basis of some types of Hebbian synaptic learning to account for the activity-dependent development of orientation maps as well as neuronal orientation selectivity. These models successfully reproduced orientation map-like spatial patterns. Nevertheless, we still have questions: (1) How does synaptic rewiring occur in the visual cortex during the formation of orderly orientation maps in early life? (2) How does visual experience contribute to the maturation of orientation selectivity of visual cortical neurons and reorganize orientation maps? (3) How does the sensitive period for orientation plasticity end? In this study, we performed animal experiments and mathematical modeling to understand the mechanisms underlying synaptic rewiring for experience-dependent formation and reorganization of orientation maps. At first, we visualized orientation maps from the intrinsic signal optical imaging in area 17 of kittens reared under single-orientation exposure through cylindrical-lens-fitted goggles. The experiments revealed that the degree of expansion of cortical domains representing the experienced orientation depends on the age at which the single-orientation exposure starts. As a result, we obtained the sensitive period profile for orientation plasticity. Next, we refined our previously proposed mathematical model for the activity-dependent self-organization of thalamo-cortical inputs on the assumption that rewiring is caused by the competitive interactions among transient synaptic contacts on the same dendritic spine. Although various kinds of molecules have been reported to be involved in such interactions, we attempt to build a mathematical model to describe synaptic rewiring focusing on brain-derived neurotrophic factor (BDNF) and its related molecules. Performing computer simulations based on the refined model, we successfully reproduced orientation maps reorganized in kittens reared under single-orientation exposure as well as normal visual experience. We also reproduced the experimentally obtained sensitive period profile for orientation plasticity. The excellent agreement between experimental observations and theoretical reproductions suggests that the BDNF-induced competitive interaction among synaptic contacts from different axons on the same spine is an important factor for the experience-dependent formation and reorganization of orientation selectivity and orientation maps.

Experience-dependent orientation plasticity in the visual cortex of rats chronically exposed to a single orientation.

We used the intrinsic signal optical imaging technique to assess the effect of orientation-restricted visual experience on response properties of the rat visual cortex. We placed young animals wearing goggles fitted with plano-convex cylindrical lenses in a stimulus-enriched environment for 3 weeks. Experienced orientation was over-represented in the visual cortex, which was associated with the under-representation of orthogonal orientation. These findings suggest that chronic exposure to a single orientation can modify orientation preferences even in rats lacking in orderly arrangement of preferred orientations.

Roles of visual experience and intrinsic mechanism in the activity-dependent self-organization of orientation maps: theory and experiment.

It is widely accepted that functional maps in the mammalian visual cortex such as ocular dominance columns and orientation columns are formed depending on neural activity. There is still, however, controversy on how much visual experience contributes to the map formation during development. In the present study, we address this issue from mathematical modeling and experimental investigation. Using a model of activity-dependent self-organization of geniculo-cortical afferent inputs, we showed that spontaneous activity in the LGN can produce orientation maps, while the exposure to drifting gratings results in sharply segregated orientation maps as observed in cat visual cortex. The restricted exposure to a single orientation of the grating led to the over-representation of the exposed orientation, which was moderated by the contribution of learning based on the spontaneous activity. These theoretical results were confirmed by intrinsic optical recordings from area 18 of kittens reared under various visual conditions.

Constraint on the number of synaptic inputs to a visual cortical neuron controls receptive field formation.

To date, Hebbian learning combined with some form of constraint on synaptic inputs has been demonstrated to describe well the development of neural networks. The previous models revealed mathematically the importance of synaptic constraints to reproduce orientation selectivity in the visual cortical neurons, but biological mechanisms underlying such constraints remain unclear. In this study, we addressed this issue by formulating a synaptic constraint based on activity-dependent mechanisms of synaptic changes. Particularly, considering metabotropic glutamate receptor-mediated long-term depression, we derived synaptic constraint that suppresses the number of inputs from individual presynaptic neurons. We performed computer simulations of the activity-dependent self-organization of geniculocortical inputs with the synaptic constraint and examined the formation of receptive fields (RFs) of model visual cortical neurons. When we changed the magnitude of the synaptic constraint, we found the emergence of distinct RF structures such as concentric RFs, simple-cell-like RFs, and double-oriented RFs and also a gradual transition between spatiotemporal separable and inseparable RFs. Thus, the model based on the synaptic constraint derived from biological consideration can account systematically for the repertoire of RF structures observed in the primary visual cortices of different species for the first time.