Experience-dependent changes in function and anatomy of adult barrel cortex

Manipulations of sensory input to vibrissal mechanoreceptors can modify columnar functioning of the barrel cortex in adult animals. In mice, partial vibrissectomy sparing one row of vibrissae in young adults results 7 days later in an increase in the functional cortical column activated by the spared whiskers and visualized with 2-deoxyglucose autoradiography. The increase in the extent of the labelled area is visible in all cortical layers, but particularly in layer V, where the metabolic labelling is more intense in the representation of the spared vibrissae. Two months after vibrissectomy the enlargement of the labelled area is accentuated. Deprivation of a row of vibrissae results in a decrease in the areal extent of its cortical representation. Investigations of cortico-cortical connections carried out in living slices of the barrel cortex of mice 2 months after vibrissectomy sparing one row of whiskers, revealed elongation and increased branching of axons originating in the spared cortical column. The dendritic spine density was increased on the basal dendrites of layer V pyramidal neurons of the spared column and decreased on layer III apical dendrites of the deprived column. Thus, prolonged changes in functional activation of adult barrel cortex are accompanied by rearrangement of cortico-cortical circuitry.     

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [14C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine (l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.     

Neonatal serotonin depletion modifies development but not plasticity in rat barrel cortex

Effects of serotonin depletion (induced by neonatal injection of 5,7-dihydroxytryptamine) upon dimensions of cortical barrels and their metabolic activation, and upon effects of neonatal vibrissectomy sparing row C, were examined in 1-month-old rats. Dimensions of row C barrels, and of [14C]2-deoxyglucose (2-DG) labelling in the cortex obtained after stimulation of the row C vibrissae, were measured. Serotonin depletion did not change dimensions of barrels, but reduced the extent of 2-DG labelling of cortical representation of the row C whiskers by 30%. Vibrissectomy sparing this row resulted in an expansion of the row C barrels and of 2-DG labelling in the barrel cortex that were similar in both control and serotonin-depleted rats.     

GABAergic neurons in barrel cortex show strong, whisker-dependent metabolic activation during normal behavior

Electrophysiological data from the rodent whisker/barrel cortex indicate that GABAergic, presumed inhibitory, neurons respond more vigorously to stimulation than glutamatergic, presumed excitatory, cells. However, these data represent very small neuronal samples in restrained, anesthetized, or narcotized animals or in cortical slices. Histochemical data from primate visual cortex, stained for the mitochondrial enzyme cytochrome oxidase (CO) and for GABA, show that GABAergic neurons are more highly reactive for CO than glutamatergic cells, indicating that inhibitory neurons are chronically more active than excitatory neurons but leaving doubt about the short-term stimulus dependence of this activation. Taken together, these results suggest that highly active inhibitory neurons powerfully influence relatively inactive excitatory cells but do not demonstrate directly the relative activities of excitatory and inhibitory neurons in the cortex during normal behavior. We used a novel double-labeling technique to approach the issue of excitatory and inhibitory neuronal activation during behavior. Our technique combines high-resolution 2-deoxyglucose (2DG), immunohistochemical staining for neurotransmitter-specific antibodies, and automated image analysis to collect the data. We find that putative inhibitory neurons in barrel cortex of behaving animals are, on average, much more heavily 2DG-labeled than presumed excitatory cells, a pattern not seen in animals anesthetized at the time of 2DG injection. This metabolic activation is dependent specifically on sensory inputs from the whiskers, because acute trimming of most whiskers greatly reduces 2DG labeling in both cell classes in columns corresponding to trimmed whiskers. Our results provide confirmation of the active GABAergic cell hypothesis suggested by CO and single-unit data. We conclude that strong activation of inhibitory cortical neurons must confer selective advantages that compensate for its inherent energy inefficiency.     

Experience-dependent plasticity in adult rat barrel cortex

This study tested the hypothesis that the receptive fields (RFs) of neurons in the adult sensory cortex are shaped by the recent history of sensory experience. Sensory experience was altered by a brief period of "whisker pairing": whiskers D2 and either D1 or D3 were left intact, while all other whiskers on the right side of the face were trimmed close to the fur. The animals were anesthetized 64-66 h later and the responses of single neurons in contralateral cortical barrel D2 to stimulation of whisker D2 (the center RF) and the four neighboring whiskers (D1, D3, C2, and E2; the excitatory surround RF) were measured. Data from 79 cells in four rats with whiskers paired were compared to data from 52 cells in four rats with untrimmed whiskers (control cases). During the period of whisker pairing, the RFs of cells in barrel D2 changed in three ways: (i) the response to the center RF, whisker D2, increased by 39%, (ii) the response to the paired surround RF whisker increased by 85-100%, and (iii) the response to all clipped (unpaired) surround RF whiskers decreased by 9-42%. In the control condition, the response of barrel D2 cells to the two neighboring whiskers, D1 and D3, was equal. After whisker pairing, the response to the paired neighbor of D2 was more than twice as large as the response to the cut neighbor of D2. These findings indicate that a brief change in the pattern of sensory activity can alter the configuration of cortical RFs, even in adult animals.     

The expression of B-50/GAP-43 and GFAP after bilateral olfactory bulbectomy in rats

In the present study we investigated the effect of a two-stage bilateral lesion of the olfactory bulb (OB) in rats on the regeneration ability of peripheral olfactory neurons and their reinnervation capacity in the spared OB. The outgrowth of newly-generated olfactory axons as well as the maturation of their terminal synaptic field was detected by immunohistochemistry of the growth-associated phosphoprotein B-50/GAP-43. In addition, the glial response to the surgery was monitored by an immunohistochemical marker for astrocytes, glial fibrillary acidic protein (GFAP). In neonatal rats (P3-P5), the right OB was removed, then three months later the contralateral side was ablated. Six days after the second operation the animals were transcardially perfused. Their brains were embedded in paraplast, serially sectioned and processed for histological and immunohistochemical observations. After neonatal OB ablation, homogeneous B-50-immunoreactivity (BIR) was found in the forebrain, olfactory axons and ectopic glomeruli localized in the small OB remnant-like structures and in the regenerated neuroepithelium. A strong GFAP response was revealed in the brain cortex as well as in the newly-formed olfactory axons and glomeruli-like structures of the OB remnants. After adult OB ablation strong BIR was observed in olfactory axons, while remaining glomerular structures were only faintly stained. The neuroepithelium revealed signs of massive degenerative processes with a substantial decrease in BIR. The GFAP-positive astrocytes were scattered throughout the entire OB remnant and were prominent in the glomeruli-like structures and adjacent frontal cortex. In the present study, we applied GAP-43 and GFAP immunohistochemistry to characterize the responses of individual olfactory components after two-stage olfactory bulbectomy. Furthermore, this model of OB ablation characterized by two immunohistochemical markers could elucidate certain molecular mechanisms involved in the regeneration and/or plasticity of the olfactory system.     

Dendritic pattern in mouse barrel field after a neonatal vibrissal follicles removal: MAP-2 immunohistochemistry

A distribution of dendrites was studied in mouse barrel field after a neonatal unilateral partial lesion of vibrissal follicles using anti-MAP-2 immunohistochemistry. The effect of a neonatal vibrissal follicles removal was studied in adult mice: barrels corresponding to intact follicles were enlarged whereas those representing removed follicles had not developed. MAP-2 immunopositive profiles were considered to be dendritic clusters and their packing density (a number per unit area) was calculated in an enlarged barrel and compared to a control barrel in a contralateral hemisphere. A decrease in the packing density of large dendritic clusters (area over 10 microns 2), presumably arising from layer V, was observed in an enlarged barrel in comparison to its control counterpart. This result may indicate a rearrangement of a dendritic pattern in mouse barrel field after a selective neonatal lesion of vibrissal follicles.     

Unmyelinated innervation of sinus hair follicles in rats

Unmyelinated nerve fibres comprise approximately one third of the innervation of rodent sinus hair follicles but their function is unknown. They may play a role as high-threshold sensory fibres, or may be autonomic efferents controlling the vascular sinus. In the present experiments capsaicin and surgical sympathectomy were used to establish whether these unmyelinated fibres are afferent fibres or autonomic efferents. The deep vibrissal nerves of mystacial follicles (C1 and C4) and a non-mystacial follicle (the postero-orbital, PO) were assessed in normal adult animals (n = 6) and compared with those treated with neonatal capsaicin (n = 6) or bilateral superior cervical ganglionectomy (n = 7). In capsaicin-treated animals, counts of fibres in the deep vibrissal nerves from all follicles showed normal numbers of myelinated axons, but approximately 80% reduction in unmyelinated fibres (normal mean +/- SD: C1 94 +/- 10, C4 89 +/- 9, PO 85 +/- 6; after neonatal capsaicin: C1 17 +/- 8, C4 16 +/- 6, PO 18 +/- 6; n = 6, P < 0.001 for all follicles). After sympathectomy there was no significant reduction in myelinated or unmyelinated fibre numbers. Labelling of PO follicles with WGA-HRP showed minimal numbers of labelled cells (0-10) within the superior cervical ganglion, also suggesting minimal sympathetic innervation. This sparse sympathetic supply to the follicle was further demonstrated by a lack of tyrosine hydroxylase reactivity within the follicle complex; tissues outside the dermal capsule showed reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishment of patterned thalamocortical connections does not require nitric oxide synthase

Subplate neurons are early-generated neurons that project into the overlying neocortex and are required for the formation of ocular dominance columns. A subset of subplate neurons express nitric oxide synthase (NOS) and produce nitric oxide (NO), a neuronal messenger thought to be involved in adult hippocampal synaptic plasticity and also in the establishment of certain specific connections during visual system development. Here, we examine whether the NOS-containing subplate neurons are involved in ocular dominance column formation in the ferret visual system. Ocular dominance columns form in ferrets between postnatal day 35 (P35) and P60. NOS expression in the visual subplate is low at birth, increases to a maximum at the onset of ocular dominance column formation, and falls thereafter. Nevertheless, blockade of NOS with daily injections of nitroarginine from P14 to P56 fails to prevent the formation of ocular dominance columns, although NOS activity is reduced by >98%. To test further a requirement for NOS in the patterning of connections during CNS development, we examined the cortical barrels in the somatosensory system of mice carrying targeted disruptions of NOS that also received injections of nitroarginine; cortical barrels formed normally in these animals. In addition, barrel field plasticity induced by whisker ablation at birth was normal in nitroarginine-injected NOS knock-out mice. Thus, despite the dynamic regulation of NOS in subplate neurons, NO is unlikely to be essential for the patterning of thalamocortical connections either in visual or somatosensory systems.     

Galactolipase and chilling sensitivity of plants

We assessed the effects of a dietary protein restriction (5% vs. 20% casein in diet) initiated at conception and imposed during the first 2 weeks of rat gestation on postnatal brain development. At the end of the malnutrition period, protein-restricted animals exhibited significantly smaller fetal body weight and brain cortical thickness than controls. At birth and thereafter, body weight was normalized in the progeny. Similarly, brain weight and cytoarchitecture were normal in postnatal animals. In contrast, we observed, during the first 2 postnatal weeks, several abnormalities of brain development which affected all the studied areas for most of the studied parameters: (i) delayed astrocytogenesis as shown by a reduced GFAP staining; (ii) delayed production of hyaluronan in the extracellular matrix studied with binding of biotinylated hyaluronectin; (iii) abnormal neuronal differentiation as shown by reduced expression of MAP-5 and increased expression of MAP-1; (iv) abnormal synaptogenesis as shown by the increased expression of synaptophysin in the basal ganglia; (v) decreased programmed cell death. In adult prenatally protein-restricted animals, all the above parameters were normalized excepted MAP-1 labeling which remained high. In addition, we observed slight alterations of the ventilatory response to hypoxia in adult animals. The present study demonstrates that early protein malnutrition during embryonic development induces multiple, transient alterations of brain development. However, the almost complete normalization in adults of brain architecture and differentiation as well as our physiological data strongly suggest a remarkable plasticity of the developing brain following an early aggression.     

Local anesthetic treatment significantly attenuates acute pain responding but does not prevent the neonatal injury-induced reduction in adult spinal behavioral plasticity.

Recent findings indicate that neonatal injury results in decreased spinal plasticity in adult subjects (E. E. Young, K. M. Baumbauer, A. E. Elliot, & R. L. Joynes, 2007). Previous research has shown that acute manipulations of pain processing (i.e., administration of formalin, carrageenan, capsaicin) result in a loss of spinal behavioral plasticity (A. R. Ferguson, E. D. Crown, & J. W. Grau, 2006). Moreover, neonatal injury results in a lasting reduction in adult spinally mediated plasticity resembling the deficit seen following acute manipulations in adults (E. E. Young et al., 2007). The present study was designed to determine whether the effects of neonatal injury could be prevented by lidocaine administration during the initial healing period. Subjects (injured or uninjured) received lidocaine or saline on 1 of 4 administration schedules (preinjury only, postinjury only, for 24 hr postsurgery, or for 72 hr postsurgery). Results demonstrated that lidocaine administration did not prevent the hypersensitivity and reduced spinal plasticity associated with neonatal injury. This suggests that (a) the mechanisms underlying neonatal injury are independent of peripheral input in the initial healing period and (b) lidocaine is ineffective at preventing long-term spinal plasticity changes following neonatal injury. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

BDNF and NT-3 applied in the whisker pad reverse cortical changes after peripheral deafferentation in neonatal rats

It has been known for a long time that subcortical input drives the specification of cortical areas. Molecular signals mediating this instructive effect from the periphery are poorly understood. In foetal or neonatal rats, ablation of whisker follicles, transection of the infraorbital nerve, inhibition of axonal transport, but not impulse activity blockade, prevent formation of barrels in the primary somatosensory cortex (S1). These findings suggest that a chemical signal, possibly arising from the skin or the follicle, may be responsible for somatotopic pattern formation in S1. Neurotrophins promote survival and differentiation of primary sensory neurons, and are expressed in the whisker pad during development. Neonatal rats received gelfoam impregnated with NGF, BDNF or NT-3 under the whisker pad following surgical denervation of whisker rows D and E on P0. Barrel formation in S1 was assessed on P7 by acetylcholinesterase histochemistry and 5-HT-immunohistochemistry. BDNF and NT-3, but not NGF, promoted development of the cortical barrels corresponding to denervated whiskers. Furthermore, BDNF and NT-3 prevented the lesion-induced expansion of row C barrels, while NGF appeared to promote row C expansion. Our results suggest that BDNF and NT-3 arising from the whisker pad are involved in the formation and/or maintenance of the barrel pattern in S1. These findings are potentially relevant for the prevention of sensory disturbances possibly due to reorganization of central sensory circuits after peripheral nerve lesions in humans.     

Differential cholinoceptor subtype-dependent activation of signal transduction pathways in neonatal versus adult rat atria

In this study, we investigated the expression and distribution of muscarinic cholinergic receptors (mAChRs) and the different signaling pathways associated with mAChR activation in atria isolated from adult and neonatal rats. Carbachol stimulation of mAChRs in both neonatal and adult rat atria led to a negative inotropic response with activation of phosphoinositide hydrolysis, an increase in cyclic GMP levels, and a decrease in cyclic AMP production. However, compared with adult atria, neonatal atria showed hypersensitivity in the contractile effect induced by carbachol. Pharmacological analysis with mAChR antagonists indicated that M1 and M2 mAChR subtypes are important mediators of the response to carbachol in neonatal atria. In contrast, in adult atria the effect of the agonist was coupled only to the M2 mAChR subtype. Moreover, an increased number of total mAChRs was labeled in neonatal atrial membranes compared with those of adults. Although a predominant M2 mAChR population is expressed in atria at both stages of development studied, competition binding parameters calculated for carbachol indicated the presence of high-affinity binding sites, with higher affinity in neonates than in adults. These results suggest that the differences observed between neonatal and adult atria in their response to a cholinergic agonist may be related to differential expression of mAChR subtypes and/or changes in functional coupling of mAChR subtypes during development.     

Neonatal whisker removal reduces the discrimination of tactile stimuli by thalamic ensembles in adult rats

Simultaneous recordings of up to 48 single neurons per animal were used to characterize the long-term functional effects of sensory plastic modifications in the ventral posterior medial nucleus (VPM) of the thalamus following unilateral removal of facial whiskers in newborn rats. One year after this neonatal whisker deprivation, neurons in the contralateral VPM responded to cutaneous stimulation of the face at much longer minimal latencies (15.2 +/- 8.2 ms, mean +/- SD) than did normal cells (8.8 +/- 5.3 ms) in the same subregion of the VPM. In 69% of these neurons, the initial sensory responses to stimulus offset were followed for up to 700 ms by reverberant trains of bursting discharge, alternating in 100-ms cycles with inhibition. Receptive fields in the deafferented VPM were also atypical in that they extended over the entire face, shoulder, forepaw, hindpaw, and even ipsilateral whiskers. Discriminant analysis (DA) was then used to statistically evaluate how this abnormal receptive field organization might affect the ability of thalamocortical neuronal populations to "discriminate" somatosensory stimulus location. To standardize this analysis, three stimulus targets ("groups") were chosen in all animals such that they triangulated the central region of the "receptive field" of the recorded multineuronal ensemble. In the normal animals these stimulus targets were whiskers or perioral hairs; in the deprived animals the targets typically included hairy skin of the body as well as face. The measured variables consisted of each neuron's spiking response to each stimulus differentiated into three poststimulus response epochs (0-15, 15-30, and 30-45 ms). DA quantified the statistical contribution of each of these variables to its overall discrimination between the three stimulus sites. In the normal animals, the stimulus locations were correctly classified in 88.2 +/- 3.7% of trials on the basis of the spatiotemporal patterns of ensemble activity derived from up to 18 single neurons. In the deprived animals, the stimulus locations were much less consistently discriminated (reduced to 73.5 +/- 12.6%; difference from controls significant at P < 0.01) despite the fact that much more widely spaced stimulus targets were used and even when up to 20 neurons were included in the ensemble. Overall, these results suggest that neonatal damage to peripheral sense organs may produce marked changes in the physiology of individual neurons in the somatosensory thalamus. Moreover, the present demonstration that these changes can profoundly alter sensory discrimination at the level of neural populations in the thalamus provides important evidence that the well-known perceptual effects of chronic peripheral deprivation may be partially attributable to plastic reorganization at subcortical levels.     

Alterations in receptive field properties of superior colliculus cells produced by visual cortex ablation in infant and adult cats

To determine if functional alterations in the superior colliculus might account for recovery of visual behaviors following visual cortex removal in infant cats, the receptive field characteristics of single units in the superior colliculus of cats whose visual cortex was removed within the first week of life were compared with those of cats which sustained visual cortex lesions in adulthood and with those of normal cats. In the normal superior colliculus, 90% of all cells responded to moving stimuli irrespective of shape or orientation. Sixty-four percent of these units were directionally selective, responding well to movement in one direction but poorly or not at all to movement in the opposite direction. Ninety percent of units were binocular, the vast majority of these responding equally to stimulation of either eye or showing only slight preference for stimulation of the contralateral eye. Responses to stationary flashes of light were observed in only 33% of all visually activated cells in the normal superior colliculus. After visual cortex ablation in adult cats, only six percent of movement sensitive cells were directionally selective. Binocular preference was shifted following adult visual cortex lesions such that sixty percent of all cells responded exclusively or predominantly to stimulation of the contralateral eye. Seventy-one percent of all visually responsive units responded to stationary lights flashed on or off within their receptive field boundaries. Lesions limited primarily to area 17 had the same effect as larger lesions of visual cortex. Infant visual cortex lesions resulted in receptive field alterations similar to those observed after adult ablation. Only fifteen percent of motion sensitive units were directionally selective. Seventy-one percent responded exclusively or predominantly to stimulation of the contralateral eye. Seventy-six percent of visually responsive cells were activated by stationary light. Lesions largely confined to area 17 produced the same alterations as more extensive lesions of visual cortex. Thus, no evidence was found that the superior colliculus is involved in the functional reorganization presumed to occur following visual cortex ablation in infant cats. Recovery of visual behaviors following neonatal injury may therefore not involve alterations in the receptive fields of single cells.     

Effect of neonatal capsaicin and infraorbital nerve section on whisker-related patterns in the rat trigeminal nucleus

In the present study, we investigated the effect of neonatally administered capsaicin on whisker-related pattern formation in the rat trigeminal complex. Both normal whisker-related patterns of barrelettes and the modified patterns seen after neonatal section of the infraorbital nerve were assessed. Capsaicin caused no change in the pattern or size of cytochrome oxidase (CO) barrelettes in the principal trigeminal nucleus (Vp) or trigeminal nucleus interpolaris (Vi) or caudalis (Vc). Injections of horseradish peroxidase (HRP) or wheatgerm agglutinin conjugated to HRP (WGA-HRP) into the posteroorbital (PO) whisker follicle in vehicle-treated animals showed that WGA labelled a larger number of trigeminal ganglion cells than HRP (203 +/- 23; cf. 158 +/- 19), with an increased labelling of small-diameter neurons (HRP: 25.9 +/- 7.7 microm; WGA: 23.2 +/- 7.2 pm). Capsaicin caused a loss of smaller diameter cells but had no effect on the location, cross-sectional area, or rostrocaudal extent of the transganglionically labelled HRP terminations in Vp, Vi, Vc, and cervical dorsal horn. WGA-HRP labelling revealed similar, but less dense, central terminal areas as HRP and an additional area of superficial terminals in the caudal medulla; these were also unaffected by capsaicin treatment. After infraorbital nerve section, CO patches and transganglionically labelled afferent terminations, corresponding to innervated nonmystacial whiskers, were approximately doubled in size. Capsaicin had no effect on the increased size of these spared whisker patches or their afferent terminal areas. These results suggest that barrelette formation is not dependent on unmyelinated afferents and that the changes in response properties seen after capsaicin, such as increased receptive fields, reflect functional changes rather than anatomical expansion of afferent terminal areas.     

Hormonal modulation of genital reflexes in male and masculinized female dogs.

When testosterone propionate (TP) is administered to adult, neonatally castrated male dogs and to adult females with masculinized genitalia produced by prenatal and neonatal exposure to androgen, both types of animals are unsuccessful in their attempts to copulate with receptive females. In the present experiment, 6 neonatally castrated male and 10 genitally masculinized female beagles were tested before and after TP treatment for responses to manual stimulation of the genitalia. An additional experimental group consisted of 6 males castrated as adults, and there was a control group of 5 normal males. After a series of TP injections (5 mg/kg), neonatally castrated males, adult castrates, and genitally masculinized females exhibited complete and strong erectile and ejaculatory reflexes. Erect penis lengths of neonatally castrated males and masculinized females were significantly shorter than those of normal males or of males castrated as adults. It is suggested that the failure of males castrated at birth, and of genitally masculinized females, to insert and lock when mounting receptive females is due to incomplete penile development and not to incomplete "organization" of spinal reflex mechanisms. (12 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Possible effect of pneumoperitoneum on the spreading of colon cancer tumor cells

Development of the central somatosensory system is profoundly modulated by the sensory periphery. Cauterization of facial whiskers alters the segregation pattern of barrels in rodents only during a few days just after birth (critical period). Although a molecular basis of the segregation of barrel neurons and the critical period for the anatomical plasticity observed in layer IV barrel neuron is not clear yet, the accumulating evidence suggests that neurotrophins modulate synaptic connections including central nervous system. In this study, we showed by in situ hybridization that mouse barrel side neurons express brain-derived neurotrophic factor (BDNF) mRNA and both catalytic and non-catalytic forms of trkB mRNA. Cautery of row C vibrissae on the right side of the face within 24 h after birth (post natal day 0, PND0) reduced the expression of BDNF and trkB mRNA from the division region between the contralateral row C barrels at PND7. The vibrissae in row A, C, and E were cauterized at PND0 followed by quantitative RT-PCR for BDNF and trkB mRNA with total RNA isolated from the barrel region at PND7. The result showed that BDNF, but not trkB, mRNA was increased several-fold in the contralateral barrel region. These data suggest that the expression of BDNF mRNA is differentially regulated between injured barrels and actively innervated barrels. The differential expression of the mRNA encoding neurotrophins and their receptors may be important in regulating the injury-dependent re-segregation of barrels.     

Neuronal subpopulations of developing rat hippocampus containing different calcium-binding proteins behave distinctively in trimethyltin-induced neurodegeneration

The present study investigates, by immunocytochemistry, the behavior of different neuronal subpopulations of the developing rat hippocampus, selectively labeled by the calcium-binding proteins calbindin D28-k (CB), parvalbumin (PV), and calretinin (CR), in neurodegenerative processes induced by the neurotoxicant trimethyltin (TMT). Previous studies on adult rats indicated that CB-immunoreactive (IR) neurons were affected by TMT, while PV- and CR-IR neurons were selectively spared. The present findings show that only CR-IR neurons are spared in developing rats, and in addition the number of CR-IR neurons are significantly higher in the DG of treated animals. On the contrary, PV-IR neurons, spared in adult rats, were affected by TMT during development. CB-IR neurons were affected also in developing rats, as in adults. The different postnatal time-courses of calcium-binding protein expression in relationship to the time of TMT administration (presence of CR but absence of PV) could have a role in the different behavior of CR- and PV-IR cells in developing rats.     

Characterization of the effect of 2-deoxy-D-glucose(2-DG) on the immune system

This study was designed to characterize the effects of the metabolic stress of administration of 2-deoxy-d-glucose (2-DG, 500 mg/kg) on immune function. Male Lewis rats were exposed to one or five injections (one every 48 h) of 2-DG. Control rats received saline injections. Administration of 2-DG induced a reduction of total leukocytes in the spleen, thymus, and blood. The reduction was most prominent in animals that received five injections of 2-DG. The ratio of CD4(+)/CD8(+) in the spleen was decreased due to a significant increase of CD8(+) T-cell subpopulation. Additionally, 2-DG induced a suppression of mitogenic responsiveness and IFN-gamma production in both whole blood and spleen lymphocytes. The production of IL-1 and IL-2 was significantly reduced in the blood, but not in the spleen. Conversely, there was a significant increase in nitric oxide production in cultures of Con A-, PHA-, and LPS-stimulated splenocytes from 2-DG-injected animals compared with saline-injected controls. In blood cultures stimulated with Con A and PHA, the nitric oxide production of the group that received five injections of 2-DG was significantly higher than in the group that received one injection of 2-DG or saline. These results demonstrated that the metabolic stress 2-DG induced a downregulation of Th 1 cellular immune function in a manner similar to physical and psychological stressors. Additionally, the use of 2-DG in rats provided an important model with which to study metabolic stress.