Monocular visual deprivation at the critical period modulates photic evoked responses

Photic evoked responses were recorded from the striate cortex of Long-Evens hooded normal (control) rats and from monocular visual deprivation (MD) rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provide comparison between the contralateral and the ipsilateral striate cortex with relation to the monocular deprived eye. The AVER recorded following binocular photic stimulation after 1 month of monocular deprivation demonstrated that the two visual cortexes responded differently. In the contralsteral hemisphere of the visual cortex (related to the MD eye), allthree components (P2, N2 and P3) of the AVER of the MD rats had significant increases M their peak amplitude as compared to the control recordings. In the ipsilateral cortex, the amplitude of component p2 and N2 was significantly reduced as a result of 1 month of MD. Comparing the AVER amplitudes of the two homotopic sites of the visual cortex obtained from the control group reveals no differences between the two hemispheres but markedly significant differences In P2, N2 and P3 components for the MD group. Based on the literature, the possibility that the monocular visual deprivation at the critical period in early developmental stage modulates the AVER as a result from the neurocytolopical alteration from ailering of GABA and ACh within the striate cortex was discussed. In conclusion, the AVER is a reliable and practical method for studying the effects of monocular deprivation and neuroplasticity in the rat visual cortex.     

Effects of monocular occlusion and diffusion on visual system development in the cat

The effects of two forms of monocular deprivation (occlusion or diffusion) on visual system development were investigated. One group of cats monocularly deprived of all form stimulation but permitted diffuse light stimulation (diffusion, n = 4) during development showed a pattern of deficits similar to those reported for monocularly sutured cats. Most cells in the visual cortex were driven exclusively by the non-deprived eye and there were eye-specific deficits in X-cell acuity, proportion of Y-cells, and cell body size (binocular and monocular segment) in the lateral geniculate nucleus (LGN). A second group of cats monocularly deprived of all form and light stimulation (occlusion, n = 4) during development showed a less severe pattern of deficits. There was no acuity loss in LGN X-cells driven by the deprived eye, and cell body shrinkage was of smaller magnitude than in diffusion reared cats and was restricted to the binocular segment. Cortical deficits and LGN Y-cell loss were similar in the two groups. The results are consistent with the idea that monocular occlusion produces only deficits due to binocular competition while monocular diffusion reflects the combined effects of binocular competition and abnormal stimulation.     

Ultrastructural effects of monocular deprivation in the neuropil of nucleus rotundus in the zebra finch: a quantitative electron microscopic study

Ultrastructural effects of monocular deprivation starting at hatching have been studied in the neuropil of nucleus rotundus, the thalamic visual relay station of the tectofugal pathway in birds. Synaptic density, presynaptic terminal size, and length of postsynaptic density (PSD) have been quantified in juvenile (20-day) and adult (100-day) zebra finches. These parameters are mature in 20-day-old zebra finches when reared under normal conditions. Alterations obtained by monocular deprivation were: The synaptic density increases by 35% in the nucleus rotundus of both sides of the brain above normal values in juvenile birds. In adult birds only the deprived side maintains this hypertrophy of synaptic density (33%), the non-deprived side returns to normal values. The presynaptic terminal size remains small in the deprived nucleus of 20-day- and 100-day-old animals, whereas the non-deprived nucleus is not affected. By the age of 20 days the length of PSD in deprived and non-deprived nuclei is not reduced as much as in normally reared zebra finches. By the age of 100 days, however, the PSDs of both sides of monocularly deprived birds show a further reduction of their median length and do not differ from PSDs of zebra finches reared under normal conditions.     

Effects of monocular enucleation at birth upon learning of a vertical—horizontal discrimination in hooded rats

Previously we have demonstrated that adult albino rats with one eye removed at birth (OEB) relearn a black—white discrimination faster than those monocularly enucleated at maturity (OET) when relearning is conducted after lesioning of the visual cortex contralateral to the remaining eye (Type A experiment). This faster relearning phenomenon is considered to be one behavioral expression of the functioning of the expanded uncrossed visual pathways (expanded UXVPs) resulting from monocular enucleation at birth. However, neither OEBs nor OETs were able to master the discrimination when the experiment was conducted without previous learning following the same surgical treatment (Type B experiment). We hypothesized that this occurs because the cues to discriminate might be close to the threshold of discrimination for either the normal UXVPs or the expanded UXVPs. In order to gain insight into the hypothesis, the present study was undertaken using hooded rats as subjects which genetically possess larger and presumably more efficient functioning UXVPs. The questions addressed were as follows: 1) Whether or not the UXVPs can mediate a vertical—horizontal discrimination in OEBs and OETs. 2) If they can, is there any difference in the upper limit of discrimination capacity between the normal UXVPs and the expanded UXVPs? Three experiments were carried out. In the Type A experiment OEBs relearned discrimination of the 10-mm stripes [0.44 cycles/degree (c/d)] faster than OETs (Experiment 1), yet in the Type B experiment neither OEBs nor OETs were capable of acquiring that discrimination (Experiment 2). However, they could originally master the discrimination equally well when the width of stripes was broadened to 30 mm (0.15 c/d). And when the width of stripes was systematically reduced thereafter, the width of the smallest stripes for the expanded UXVPs to discriminate was found to be 6 mm (0.73 c/d) and that for the normal UXVPs 10 mm (0.44 c/d) [Experiment 3]. These findings were discussed in relation to the hypothesis advanced on our previous data in albino rats.     

Susceptibility to monocular deprivation following immersion in darkness either late into or beyond the critical period

An extended duration of darkness starting near the time of birth preserves immature neuronal characteristics and prolongs the accentuated plasticity observed in young animals. Brief periods of complete darkness have emerged as an effective means of restoring a high capacity for neural plasticity and of promoting recovery from the effects of monocular deprivation (MD). We examined whether 10 days of darkness imposed in adulthood or beyond the peak of the critical period could rejuvenate the ability of MD to reduce the size of neuron somata within deprived layers of the cat dorsal lateral geniculate nucleus (dLGN). For adult cats subjected to 10 days of darkness before 7 days of MD, we observed no alteration in neuron size or neurofilament labeling within the dLGN. At 12 weeks of age, MD that followed immediately after 10 days of darkness produced an enhanced reduction of neuron soma size within deprived dLGN layers. For this age we observed that 10 days of darkness also enhanced the loss of neurofilament protein within deprived dLGN layers. These results indicate that, although 10 days of darkness in adulthood does not enhance the susceptibility to 7 days of MD, darkness imposed near the trailing edge of the critical period can restore a heightened susceptibility to MD more typical of an earlier developmental stage. The loss of neurofilament in juveniles exposed to darkness prior to MD suggests that the enhanced capacity for structural plasticity is partially rooted in the ability of darkness to modulate molecules that inhibit plasticity. J. Comp. Neurol. 524:2643–2653, 2016. © 2016 Wiley Periodicals, Inc.     

Effects of autoimmune NGF deprivation in the adult rabbit and offspring

An experimental autoimmune approach to the production of nerve growth factor deprivation, which we have previously described in the rat and guinea pig, has been applied to the rabbit. This species was chosen for study because of several potential advantages. The rabbit produces large litters and has a relatively short gestation period. More importantly, rabbits generate high titers of antibody against mouse NGF and large amounts of maternal antibody are passively transferred to the developing rabbit fetus compared to most other species, particularly the rat. The sympathetic nervous system of adult rabbit immunized against mouse NGF underwent degeneration with up to an 85% decrease in neuronal numbers in the superior cervical ganglion after 10 months of immunization, thus providing further evidence that NGF is required for the survival of mature sympathetic neurons. Despite the fact that newborn rabbits born to anti-NGF producing mothers had much higher titers of anti-NGF than did rats, the effects on the developing sympathetic and sensory nervous systems were not found to be any greater than in rats. Reductions in norepinephrine levels in the heart and spleen of adult rabbits born to anti-NGF producing mothers were greater than in small intestine. Prenatal exposure to maternal anti-NGF caused reductions (up to 70%) in the number of neurons in the dorsal root ganglia. Substance-P immunoreactivity was reduced in the substantia gelatinosa of the spinal cord of rabbit exposed to maternal anti-NGF. These changes, however, were not greater than seen in the rat. We conclide that although the rabbits offers some advantage in the study of the effects of NGF deprivation in the adult animal, it appears less well suited than the rat or guinea pig to the study of the effects of NGF deprivation on development.     

Visual split brain and monocular deprivation in kittens: differentiation between the effects of disuse and of binocular competition in visual cortex cells

To differentiate between the resulting effect of disuse, developmentally induced by deprivation, and the binocular competition effect on cortical cells, visual split brain was performed concurrently with monocular deprivation in kittens. In the experienced hemisphere of the split brain deprived cats (ipsilaterally to the non-deprived eye), there were twice as many visually responsive cortical cells than found in their inexperienced hemisphere (ipsilaterally to the deprived eye); however, these cells were equal in number to that found in the split brain controls. In the monocularly deprived control cats a relation of 3.2 was found between cells driven by the non-deprived and the deprived eye. Visual disuse, therefore, resulting from monocular deprivation, affects cortical cells under complete absence of binocular competition but is greatly enhanced by the latter.     

Retinal ganglion-cell densities and soma sizes are unaffected by long-term monocular deprivation in the cat

Three cats were raised with monocular deprivation for 5.2–7.2 years, and ganglion-cell densities and soma sizes were measured in their flat-mounted retinae. The retinae were Nissl-stained so that ganglion cells could be measured whether or not they maintained normal central projections. Measurements were made in the area centralis, peripheral binocular segment, and monocular segment of the retinae. There were no significant differences between the deprived and non-deprived retinae in the densities or soma-sizes of α cells or other (non-α) ganglion cells at any of these retinal locations. These results support the view that the most distal effects of monocular deprivation occur at the retino-geniculate contact, and they suggest that even after long-term monocular deprivation, effects in the lateral geniculate nucleus do not produce secondary, retrograde changes in the retina.     

睡眠剥夺大鼠大脑皮层和海马nNOS表达的改变在其学习记忆损伤中的作用

目的观察睡眠剥夺（SD）后,大鼠学习记忆能力及大脑皮层和海马神经元型一氧化氮合酶（nNOS）蛋白表达的变化。方法采用小平台水环境法建立大鼠SD模型。观察大鼠经过不同时间SD后,各组“Y”迷宫成绩及大脑皮层和海马nNOS阳性神经元的变化情况。结果（1）“Y”迷宫实验：3组SD组的迷宫成绩较正常笼养对照组（CC）分别下降了24．3％、17．6％和41．9％（P〈0．01）。（2）nNOS阳性神经元数目：在皮层,SDld组较CC组增加了8．7％（P〈0．01）,SD2d组和SD3d组较CC组则减少了9．0％和16．0％（P〈0．01）;在海马CA。区,3个SD组较CC组分别减少了9．4％、16．0％和22．0％（P〈0．01）。结论SD可能通过改变大鼠大脑皮层和海马CA．区nNOS蛋白的表达来损害大鼠学习记忆能力。     

TrkA activation in the rat visual cortex by antirat trkA IgG prevents the effect of monocular deprivation

It has been recently shown that intraventricular injections of nerve growth factor (NGF) prevent the effects of monocular deprivation in the rat. We have tested the localization and the molecular nature of the NGF receptor(s) responsible for this effect by activating cortical trkA receptors in monocularly deprived rats by cortical infusion of a specific agonist of NGF on trkA, the bivalent antirat trkA IgG (RTA-IgG). TrkA protein was detected by immunoblot in the rat visual cortex during the critical period. Rats were monocularly deprived for 1 week (P21–28) and RTA-IgG or control rabbit IgG were delivered by osmotic minipumps. The effects of monocular deprivation on the ocular dominance of visual cortical neurons were assessed by extracellular single cell recordings. We found that the shift towards the ipsilateral, non-deprived eye was largely prevented by RTA-IgG. Infusion of RTA-IgG combined with antibody that blocks p75^NTR (REX), slightly reduced RTA-IgG effectiveness in preventing monocular deprivation effects. These results suggest that NGF action in visual cortical plasticity is mediated by cortical TrkA receptors with p75^NTR exerting a facilitatory role.     

神经生长因子及其两种脑内促生剂对老年大鼠脑内M胆碱能受体的影响

目的 观察神经生长因子(NGF)及其两种脑内促生剂丙戊茶碱(PPF)和左旋乙酰肉毒碱(ALCAR)对老年大鼠脑中M胆碱能受体的影响，进一步探讨NGF抗衰老作用的途径和机制。方法 采用放射配体结合实验检测经脑室注射NGF和分别口服PPF和ALCAR的老年大鼠(24月龄)脑组织中M胆碱能受体的数量和亲和力。结果 脑室注射NGF和口服PPF的老年大鼠脑组织中M受体的结合容量(Bmax)明显高于对照组；而ALCAR治疗组效果不明显。结论 外源性NGF和PPF可使老年大鼠脑组织中M受体的数量增多，进而改善中枢胆碱能系统的功能。     

NGF delays rather than prevents the cholinergic terminal damage and delayed neuronal death in the hippocampus after ischemia

Cerebral ischemia induces damage of cholinergic terminals in the hippocampus, which preceded the delayed neuronal death (DND) of the CA1 pyramidal cells. We investigated the effects of nerve growth factor (NGF) on the cholinergic terminal damage after ischemia. Continuous NGF infusion (0.5 μg/7 days) into the lateral ventricle before and after 5 min ischemia prevented a decrease in choline acetyltransferase (ChAT)-immunoreactivity and disturbance of acetylcholine (ACh) release on the 4th day after ischemia, but not on day 7, i.e., NGF infusion caused delay in the progress of the cholinergic terminal damage. These findings show that the cholinergic terminal damage may result from deficiency of endogenous NGF in an ischemic brain. In addition, we investigated whether NGF would prevent the DND after ischemia. NGF infusion also caused delay in the progress of the DND until day 14. Our results suggested that the neuroprotective effect of NGF on the DND may be secondarily yielded by maintenance of communication between cholinergic terminal and the target CA1 cell, and that prevention of cholinergic terminal damage may be useful for the treatment of cerebrovascular disease.     

Altered behavioral responsivity to morphine during the periadolescent period in rats

The results of previous studies have suggested that periadolescent rats are differentially affected by catecholaminergic agents, when compared with younger or adult animals. Since dopamine-opiate interactions have been demonstrated in rats, the present study was conducted to evaluate the behavioral responsivity of periadolescent and adult rats following doses of morphine ranging from 1 to 10 mg/kg i.p. The responses measured included matrix crossings, rearing, grooming, auto-directed stereotyped behavior and gnawing, and were recorded continuously from 30 to 90 min post-injection. When indicated, scores on each measure were transformed to control for differences observed in the baseline (saline) groups. Analyses of all measures revealed a significant effect of morphine dose, although the shape of the dose-response curve differed for individual responses. In addition, those measures which might be considered locomotor responses (matrix crossing, rearing), as well as grooming, revealed significant main or interactive effects of age. In contrast, those measures characterized as stereotyped behaviors (auto-directed stereotyped behavior and gnawing) revealed no differential effect in periadolescent animals relative to adults. Since locomotor responses and stereotyped behavior have been suggested by previous research to be mediated by the mesolimbic and extrapyramidal dopamine systems, respectively, these results further support the previously suggested hypothesis of the delayed ontogeny of mesolimbic relative to extrapyramidal dopamine pathways.     

Destruction of sympathetic and sensory neurons in the developing rat by a monoclonal antibody against the nerve growth factor (NGF) receptor

The ability of the monoclonal antibody, 192-IgG, directed against the rat nerve growth factor (NGF) receptor to mimic or inhibit the actions of NGF was examined in vitro and in vivo. 192-IgG had no effect on morphology, survival, or protein synthesis rates of sympathetic neuronal cultures. When injected into newborn rats, destruction of sympathetic, but not sensory, neurons was produced. Injection prenatally produced more dramatic destruction of sympathetic neurons and, in addition, destruction of neural crest-derived sensory neurons. Therefore, although 192-IgG had no discernible effects in vitro, it produced a pattern of neuronal destruction in vivo qualitatively similar to that produced by antibodies to NGF itself.     

Behavioral and growth effects induced by low dose methamphetamine administration during the neonatal period in rats

The investigation of methamphetamine exposure during neonatal development in rats has demonstrated that long-term spatial learning deficits are induced. A previous dose-response study showed that administration of 5 mg/kg methamphetamine, four times daily from postnatal days 11 to 20 produced these deficits, although the effects were not as severe as at higher doses of 10 or 15 mg/kg. This study examined concentrations of methamphetamine at or below 5mg/kg given over the same period of time. Five different concentrations of methamphetamine (i.e., 5, 2.5, 1.25, 0.625, or 0) were administered every 2 h four times daily from postnatal days 11 to 20. Body weights, zero maze performance, and Morris water maze learning were examined. A dose-dependent decrease in body weight was observed during the period of methamphetamine administration and these lower weights continued throughout adulthood for the 5, 2.5, and 1.25 mg/kg concentrations, although the adult decreases were negligible. No differences were noted in the zero maze. In the Morris water maze during the acquisition period, dose-dependent differences in spatial orientation were seen, however non-dose related deficits were observed for other parameters. During the shifted platform phase ("reversal"), a similar dose-dependent difference in spatial orientation was observed, although no other effects were noted during this phase. Females performed worse than males regardless of treatment or the phase of learning in the Morris water maze. These data suggest that even lower doses of methamphetamine can alter learning and memory in adulthood, although with less consistent results than with doses higher than 5 mg/kg/dose. These data would caution against even casual use of methamphetamine by women during pregnancy since even low doses could alter the ability of the child to learn.     

Permanent changes in muscle and motoneurones induced by nerve injury during a critical period of development of the rat

The sciatic nerve was crushed in rats at different times during the first two weeks after birth. Following reinnervation the recovery of the fast and slow muscles and their motoneurones was compared. The main factor affecting recovery of muscle weight and tension was the age at which the nerve was crushed; the earlier the injury the greater the impairment. However, recovery also depended upon muscle type. The fast muscles, tibialis anterior and extensor digitorum longus, always recovered less well than the slow soleus muscle. The greatest difference in recovery was seen when the nerve was crushed between 3 and 6 days of age. The fatigue resistance of fast muscles was markedly increased after nerve injury at any time during the first two postnatal weeks and was greatest when the nerve crush was done soon after birth. However, this change was not just related to muscle weakness as the increase in fatigue resistance after nerve crush at 5 and 12 days was similar regardless of the difference in recovery of the muscles. Retrograde labelling of motoneurones with HRP demonstrated that about 60-70% of motoneurones innervating fast or slow muscles were lost following sciatic nerve crush at birth. It is concluded that motoneurone loss probably accounts for most of the impairment of soleus after postnatal nerve crush but only partly explains the poor recovery of fast muscles.     

Activity-dependent reduction of dopamine D2 receptors during a postnatal critical period of plasticity in rat striatum is not affected by prenatal haloperidol treatment

Motor activity induced in the Circling Training test (CT) during a postnatal (PN) critical period of plasticity (PN30-37) produces a long-lasting decrease in the number of binding sites and mRNA expression levels of the dopamine D2 receptor (D2R) in rat striatum. Prenatal exposure to the antipsychotic haloperidol also decreases postnatal levels of the striatal D2R in the offspring. We examined whether such fetal exposure to haloperidol could affect the activity-dependent reduction of the D2R system during the critical period. Half of the male offspring exposed to either haloperidol (2.5 mg/kg/day), i.p.) or saline during gestational days 5-18 were subjected to the CT during the critical period, while the remaining represented CT control animals. The adult number of binding sites and mRNA expression levels of the striatal D2R at PN90 were not changed by prenatal haloperidol treatment alone. On the other hand, only pups subjected to the CT during the critical period showed decreases in both studied parameters, regardless the prenatal treatment. These findings indicated that the postnatal reduction of the striatal D2R binding induced prenatally by haloperidol does not affect long-lasting activity-dependent plastic changes on the same receptor system elicited by motor activity in an ontogenetic critical period of plasticity in rat striatum.     

mRNA for NGF and p75 in the central nervous system of rats affected by experimental allergic encephalomyelitis

R. De Simone, A. Micera, P. Tirassa and L. Aloe (1996) Neuropathology and Applied Neurobiology 22, 54-59 mRNA for NGF and p75 in the central nervous system of rats affected by experimental allergic encephalomyelitis
In this study we measured the concentration of nerve growth factor (NGF) and the expression of NGF and the low affinity NGF-receptor (NGF-r) mRNA in the central nervous system (CNS) of rats affected by experimental allergic encephalomyelitis (EAE) during the acute phase of the disease. Significant levels of NGF protein were found in thalamus and cortex on day 13 postimmunization. Molecular analysis of the NGF gene expression and of its NGF-r revealed that they were enhanced in several regions of the CNS of EAE rats when compared with untreated animals. These results suggest a functional link between local NGF synthesis and this autoimmune inflammatory disease.     

CGRP和NGF对脑局部缺血再灌注大鼠脑组织神经元凋亡及PKCmRNA表达的调节作用

目的研究大鼠脑缺血再灌注后蛋白激酶C信使RNA(PKCmRNA)的表达,探讨降钙素基因相关肽(CGRP)和神经生长因子(NGF)对脑组织缺血再灌注的保护作用及机制。方法采用颈动脉负压分流法制作大鼠脑缺血再灌注模型,采用TUNEL法、原位杂交方法及显微图像分析检测海马及皮质内神经元凋亡和PKCmRNA的表达。结果大鼠缺血再灌注海马及顶叶皮质内神经元凋亡数及PKCmRNA反应产物较正常组增多(P<0.05),而注射CGRP或NGF后神经元凋亡数及PKCmRNA反应产物明显低于缺血再灌注组(P<0.01),二者联合应用效果更加显著(P<0.05)。结论CGRP和NGF抑制缺血神经元凋亡,参与PKCmRNA的调节,二者对缺血神经元有协同修复作用。     

Mutation of low affinity nerve growth factor receptor gene in spontaneously hypertensive and stroke-prone spontaneously hypertensive rats: one of the promising candidate genes for hypertension

There is evidence that abnormal formation of the sympathetic nervous system might be important for pathogenesis of hypertension. In the present study we analyzed nucleotide sequences of low affinity nerve growth factor receptor (LNGFR) genes in the spontaneously hypertensive rat and its stroke-prone substrain. There was a point mutation generating an amino acid substitution in signal peptide of these LNGFRs. This result suggested that the mutated LNGFR gene is one of the promising candidate genes for hypertension.