Visual Cortex Of Dark-reared Rats Research Articles

Physical exercise is required for environmental enrichment to offset the quantitative effects of dark‐rearing on the S‐100β astrocytic density in the rat visual cortex

After birth, exposure to visual inputs modulates cortical development, inducing numerous changes in all of the components of the visual cortex. Most of the cortical changes thus induced occur during what is called the critical period. Astrocytes play an important role in the development, maintenance and plasticity of the cortex as well as in the structure and function of the vascular network. Visual deprivation induces a decrease in the astroglial population, whereas enhanced experience increases it. Exposure to an enriched environment has been shown to prevent the effects of dark-rearing in the visual cortex. Our purpose was to study the effects of an enriched environment on the density of astrocytes per reference surface at the visual cortex of dark-reared rats, in order to determine if enhanced experience is able to compensate the quantitative effects of visual deprivation and the role of physical exercise on the enrichment paradigm. Pregnant Sprague-Dawley rats were raised in one of the following rearing conditions: control rats with standard housing (12-h light/dark cycle); in total darkness for the dark-rearing experiments; and dark-rearing in conditions of enriched environment without and with physical exercise. The astrocytic density was estimated by immunohistochemistry for S-100beta protein. Quantifications were performed in layer IV. The somatosensorial cortex barrel field was also studied as control. The volume of layer IV was stereologically calculated for each region, age and experimental condition. From the beginning of the critical period, astrocyte density was higher in control rats than in the enriched environment group without physical exercise, with densities of astrocytes around 20% higher at all of the different ages. In contrast, when the animals had access to voluntary exercise, densities were significantly higher than even the control rats. Our main result shows that strategies to apply environmental enrichment should always consider the incorporation of physical exercise, even for sensorial areas such as the visual area, where complex enriched experience by itself is not enough to compensate the effects of visual deprivation.

Effects of Neurotrophins on Synaptic Protein Expression in the Visual Cortex of Dark-Reared Rats

Total lack of visual experience [dark rearing (DR)] is known to prolong the critical period and delay development of sensory functions in mammalian visual cortex. Recent results show that neurotrophins (NTs) counteract the effects of DR on functional properties of visual cortical cells and exert a strong control on critical period duration. NTs are known to modulate the development and synaptic efficacy of neurotransmitter systems that are affected by DR. However, it is still unknown whether the actions of NTs in dark-reared animals involve interaction with neurotransmitter systems. We have studied the effects of DR on the expression of key molecules in the glutamatergic and GABAergic systems in control and NT-treated animals. We have found that DR reduced the expression of the NMDA receptor 2A subunit and its associated protein PSD-95 (postsynaptic density-95), of GRIP (AMPA glutamate receptor interacting protein), and of the biosynthetic enzyme GAD (glutamic acid decarboxylase). Returning dark-reared animals to light for 2 hr restored normal expression of the above-mentioned proteins almost completely. NT treatment specifically counteracts DR effects; NGF acts primarily on the NMDA system, whereas BDNF acts primarily on the GABAergic system. Finally, the action of NT4 seems to involve both excitatory and inhibitory systems. These data demonstrate that different NTs counteract DR effects by modulating the expression of key molecules of the excitatory and inhibitory neurotransmitter systems.

Visual deprivation effects on the s100β positive astrocytic population in the developing rat visual cortex: a quantitative study

After birth, exposure to visual inputs modulates cortical development, inducing numerous changes of all components of the visual cortex. Most of the cortical changes thus induced occur during what is called the critical period. Astrocytes play an important role in the development, maintenance and plasticity of the cortex, as well as in the structure and function of the vascular network. Dark-reared Sprague–Dawley rats and age-matched controls sampled at 14, 21, 28, 35, 42, 49, 56 and 63 days postnatal (dpn) were studied in order to elucidate quantitative differences in the number of positive cells in the striate cortex. The astrocytic population was estimated by immunohistochemistry for S-100β protein. The same quantification was also performed in a nonsensory area, the retrosplenial granular cortex. S-100β positive cells had adult morphology in the visual cortex at 14 dpn and their numbers were not significantly different in light-exposed and nonexposed rats up to 35 dpn, and were even higher in dark-reared rats at 21 dpn. However, significant quantitative changes were recorded after the beginning of the critical period. The main finding of the present study was the significantly lower astroglial density estimated in the visual cortex of dark-reared rats over 35 dpn as well as the lack of difference at previous ages. Our results also showed that there were no differences when comparing the measurements from a nonsensory area between both groups. This led us to postulate that the astrocytic population in the visual cortex is downregulated by the lack of visual experience.

Transplant of Schwann cells allows normal development of the visual cortex of dark-reared rats.

Visual experience is necessary for the correct development of the visual cortex. Dark-rearing from birth affects normal maturation of the functional properties of mammalian visual cortex: cortical cells show rapid habituation to repeated stimulation, decreased orientation selectivity, and enlarged receptive fields. Spatial resolution and response latency are also impaired. Recent experiments have demonstrated that visual deprivation reduces the expression of neurotrophins in the visual cortex. We formulated the hypothesis that visual experience drives the maturation of functional properties of the visual cortex by regulating cortical levels of neurotrophins. If this hypothesis is correct, exogenous supply of neurotrophins during dark-rearing from birth should prevent, or at least ameliorate, the effects of a lack of visual experience. Since Schwann cells are efficient biological minipumps of neurotrophic factors, we transplanted 1.0 or 1.5 x 10(6) Schwann cells or infused vehicle solution as a control into the lateral ventricles of 13 day old rats reared in total darkness from birth until the end of the critical period (postnatal day 45). Single-cell responses and visual-evoked potentials were recorded from the binocular zone of the primary visual cortex of each group. We found that in Schwann cell-transplanted animals all parameters tested were significantly improved upon those of dark-reared control rats and were in the range of normal adult values. Thus, Schwann cell transplant contributed to the normal development of visual response properties in the visual cortex, compensating for a complete absence of visual experience.

Gamma-aminobutyric acid and somatostatin immunoreactivity in the visual cortex of normal and dark-reared rats

Our previous single unit and ultrastructural studies of visual cortex of dark-reared rats revealed an impairment of intracortical inhibitory mechanisms [2,3,5]. Neurochemical changes in inhibitory neurotransmitter and/or neuropeptides, such as gamma-aminobutyric acid (GABA) and somatostatin (SS), respectively, may contribute to the observed alterations. The present study was designed to measure GABA and SS alterations in the visual cortex of the same dark-reared preparation, as possible neurochemical correlates of the changes seen both physiologically and anatomically in previous companion studies. In the present investigation the mean densities of GABA-and SS-immunoreactive neurons in area 17 of dark-reared rats were determined and compared to the density of those of rats reared in normal lighting conditions. Dark-rearing resulted in a significant decrease in the density of GABA-immunoreactive neurons in all cell layers of are 17 of the rat visual cortex; not limited to the thalamorecipient layer(s). There was also a higher mean density of total cortical cells in dark-reared animals. No differences, however, were seen in the density of SS-immunoreactive neurons. The alterations of GABA-immunoreactive neurons in all cortical layers agree with the altered synaptic ultrastructure and physiological responses seen in all cortical layers as reported in our previous companion studies. Taken together, these studies further support the notion of a deficit in intracortical inhibitory mechanisms in the visual cortex of dark-reared adult rats.

Effects of neurotransmitters and hormones on neuronal production of neurotrophins

The neurotrophins NGF, BDNF and NT-3 are relativelyhighly expressed by specific populations of neurons in the central nervous system. The levels of NGF and BDNF mRNAs in the rat hippocampus are up-regulated by activation of glutamate and muscarinic cholinergic receptors, whereas the gabaergic system exerts an inhibitory influence on these mRNA levels. Glucocorticoid hormones specifically increase NGF and NT-3, but not BDNF mRNA levels, in the rat hippocampus. In the rat visual cortex, BDNF mRNA, but not NGF mRNA, levels are decreased by light deprivation or after inhibiting the activity of the retinocortical pathway by tetrodotoxin. Exposure to light rapidly elevates BDNF mRNA in the visual cortex of dark-reared rats. The rapidity and specificity of changes in neurotrophin expression in neurons suggest a possible involvement of these factors in synaptic plasticity during development and in the adult brain.

Regulation of Protein Kinase C Activity by Sensory Deprivation in the Olfactory and Visual Systems

Environmental regulation of sensory function has provided an important model of plastic mechanisms mediating neural information processing. To define potential commonalities in information processing in different systems, we investigated molecular changes elicited by sensory deprivation in the developing rat olfactory and visual systems. Protein kinase C (PKC), an intracellular messenger implicated in synaptic plasticity and memory, was analyzed. Initial, developmental studies indicated that PKC activity in the soluble and particulate fractions of the olfactory bulb increased three- to fourfold from birth to 3 months of age. Unilateral olfactory deprivation prevented the developmental increase in both soluble and particulate PKC activities in the ipsilateral olfactory bulb and piriform cortex, the second-order relay. Phorbol ester binding localized PKC to intrinsic neuronal populations and their dendrites in the control and deprived bulbs. Moreover, PKC was similarly lower in the visual cortex of dark-reared rats than in light-reared controls. The changes in PKC were region specific, as activity was unchanged by either treatment in the parietal cortex, a control area that does not process primary olfactory or visual information. Our results suggest that the important intracellular messenger, PKC, is similarly regulated in entirely different sensory systems by different environmental stimuli. Consequently, different sensory systems may use common molecular mechanisms to process information.

Decreased levels of an astrocytic marker, glial fibrillary acidic protein, in the visual cortex of dark-reared rats: Measurement by enzyme-linked immunosorbent assay

An antibody to glial fibrillary acidic protein (GFAP) (an immunocytochemical marker for astrocytes) has been used in an enzyme-linked immunosorbent assay (ELISA) to determine the amount of GFAP in three visual regions, the dorsal lateral geniculate nucleus (dLGN), the superior colliculus (SC) and the visual cortex (VC) (area 17) of dark-reared (D), normal (N) and light-exposed (L) rats. In all experiments GFAP was also measured in a control non-visual region, the motor cortex (MC) (area 4). No significant differences were found in GFAP in dLGN, SC or MC between D, L or N rats. However, in the visual cortex, the amount of GFAP in N rats was significantly greater than that in D rats (by 32%).

Organization of visual pathways in normal and visually deprived cats.

Organization of visual pathways in normal and visually deprived cats.