Search

A deterioration in cognitive performance accompanies brain aging, even in the absence of neurodegenerative pathologies. However, the rate of cognitive decline can be slowed down by enhanced cognitive and sensorimotor stimulation protocols, such as environmental enrichment (EE). Understanding how EE exerts its beneficial effects on the aged brain pathophysiology can help in identifying new therapeutic targets. In this regard, the inflammatory chemokine ccl11/eotaxin-1 is a marker of aging with a strong relevance for neurodegenerative processes. Here, we demonstrate that EE in both elderly humans and aged mice decreases circulating levels of ccl11. Interfering, in mice, with the ccl11 decrease induced by EE ablated the beneficial effects on long-term memory retention, hippocampal neurogenesis, activation of local microglia and of ribosomal protein S6. On the other hand, treatment of standard-reared aged mice with an anti-ccl11 antibody resulted in EE-like improvements in spatial memory, hippocampal neurogenesis, and microglial activation. Taken together, our findings point to a decrease in circulating ccl11 concentration as a key mediator of the enhanced hippocampal function resulting from exposure to EE. A deterioration in cognitive performance accompanies brain aging, even in the absence of neurodegenerative pathologies. However, the rate of cognitive decline can be slowed down by enhanced cognitive and sensorimotor stimulation protocols, such as environmental enrichment (EE). Understanding how EE exerts its beneficial effects on the aged brain pathophysiology can help in identifying new therapeutic targets. In this regard, the inflammatory chemokine ccl11/eotaxin-1 is a marker of aging with a strong relevance for neurodegenerative processes. Here, we demonstrate that EE in both elderly humans and aged mice decreases circulating levels of ccl11. Interfering, in mice, with the ccl11 decrease induced by EE ablated the beneficial effects on long-term memory retention, hippocampal neurogenesis, activation of local microglia and of ribosomal protein S6. On the other hand, treatment of standard-reared aged mice with an anti-ccl11 antibody resulted in EE-like improvements in spatial memory, hippocampal neurogenesis, and microglial activation. Taken together, our findings point to a decrease in circulating ccl11 concentration as a key mediator of the enhanced hippocampal function resulting from exposure to EE.

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65–89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid–femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P =0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10 −3 ; P =0.009); only the latter remained significant after adjustment for confounders ( P =0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P =0.006; P =0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34 + cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa −1 ; P =0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34 + cells, and preserved carotid distensibility. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01725178.

Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline. Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.

We develop a theoretical framework that considers the role played by moral hazard and the diversity of networks and cultures in the choice of hiring channel. In favoritism contexts social networks, and particularly strong ties, are adopted as hiring channels for unskilled jobs and result in wage penalties, while otherwise the opposite happens. We estimate an endogenous switching model for the case of Senegal's manufacturing formal sector and find, consistently with our theoretical predictions in case of favoritism, that informal hiring channels are preferred to fill unskilled vacancies and are associated with a wage penalty, especially when ties are stronger.

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

Analisi del decimo libro degli Epigrammi, con lo scopo di individuare le caratteristiche strutturali della seconda edizione curata dal poeta nel 98 d.C.

A major challenge in the neuroscience field is the identification of molecules and pathways that control synaptic plasticity and memory. Dendritic spines play a pivotal role in these processes, as the major sites of excitatory synapses in neuronal communication. Previous studies have shown that the scaffold protein p140Cap localizes into dendritic spines and that its knockdown negatively modulates spine shape in culture. However, so far, there is no information on itsin vivorelevance. By using a knock-out mouse model, we here demonstrate that p140Cap is a key element for both learning and synaptic plasticity. Indeed,p140Cap−/−mice are impaired in object recognition test, as well as in LTP and in LTD measurements. Thein vivoeffects of p140Cap loss are presumably attenuated by noncell-autonomous events, since primary neurons obtained fromp140Cap−/−mice show a strong reduction in number of mushroom spines and abnormal organization of synapse-associated F-actin. These phenotypes are most likely caused by a local reduction of the inhibitory control of RhoA and of cortactin toward the actin-depolymerizing factor cofilin. These events can be controlled by p140Cap through its capability to directly inhibit the activation of Src kinase and by its binding to the scaffold protein Citron-N. Altogether, our results provide new insight into how protein associated with dynamic microtubules may regulate spine actin organization through interaction with postsynaptic density components.

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

Rho family GTPases have been implicated as important regulators of neuronal development. Rac3 is a member of this family specifically expressed in vertebrate developing neurons, where it is coexpressed with the ubiquitous Rac1 GTPase. We have previously shown that Rac3 knockout mice are viable and fertile. The Rac3 protein shows highest expression around postnatal day 7 in brain regions relevant for cognitive behaviors. In this study we find that Rac3 knockout mice do not show defects in spatial reference memory assessed with water maze task, but they show a reduced behavioral flexibility to novel situations. Analysis of explorative behavior revealed hyperactive behavior and hyperreactivity to the presentation of new stimuli, as assessed by dark/light box, emergence and novel object tests. These defects were not due to reduced visual abilities, since visual acuity and contrast sensitivity were comparable in Rac3 knockout and wildtype littermates. Our data reinforce the notion that Rho family GTPases are important for normal cognitive development, and highlight specific functions of Rac3 that cannot be compensated by the coexpressed homologous Rac1.

Adult neurogenesis is a multistep process regulated by several extrinsic factors, including neurotrophins. Among them, little is known about the role of nerve growth factor (NGF) in the neurogenic niches of the mouse. Here we analyzed the biology of adult neural stem cells (NSCs) from the subventricular zone (SVZ) of AD11 anti-NGF transgenic mice, in which the expression of the recombinant antibody aD11 leads to a chronic postnatal neutralization of endogenous NGF. We showed that AD11-NSCs proliferate 10-fold less, with respect to their control counterparts, and display a significant impairment in their ability to differentiate into β-tubulin positive neurons. We found a considerable reduction in the number of SVZ progenitors and neuroblasts also in vivo, which correlates with a lower number of newborn neurons in the olfactory bulbs of AD11 mice and a severe deficit in the ability of these mice to discriminate between different odors. We also demonstrated that, in AD11 mice, the morphology of both SVZ-resident and neurosphere-derived astrocytes is significantly altered. We were able to reproduce the AD11 phenotype in vitro, by acutely treating wild type NSCs with the anti-NGF antibody, further demonstrating that both the proliferation and the differentiation defects are due to the NGF deprivation. Consistently, the proliferative impairment of AD11 progenitors, as well as the atrophic morphology of AD11 astrocytes, can be partly rescued in vitro and in vivo by exogenous NGF addition. Altogether, our results demonstrate a causal link between NGF signaling and proper proliferation and differentiation of neural stem cells from the SVZ. Adult neurogenesis is a multistep process regulated by several extrinsic factors, including neurotrophins. Among them, little is known about the role of nerve growth factor (NGF) in the neurogenic niches of the mouse. Here we analyzed the biology of adult neural stem cells (NSCs) from the subventricular zone (SVZ) of AD11 anti-NGF transgenic mice, in which the expression of the recombinant antibody aD11 leads to a chronic postnatal neutralization of endogenous NGF. We showed that AD11-NSCs proliferate 10-fold less, with respect to their control counterparts, and display a significant impairment in their ability to differentiate into β-tubulin positive neurons. We found a considerable reduction in the number of SVZ progenitors and neuroblasts also in vivo, which correlates with a lower number of newborn neurons in the olfactory bulbs of AD11 mice and a severe deficit in the ability of these mice to discriminate between different odors. We also demonstrated that, in AD11 mice, the morphology of both SVZ-resident and neurosphere-derived astrocytes is significantly altered. We were able to reproduce the AD11 phenotype in vitro, by acutely treating wild type NSCs with the anti-NGF antibody, further demonstrating that both the proliferation and the differentiation defects are due to the NGF deprivation. Consistently, the proliferative impairment of AD11 progenitors, as well as the atrophic morphology of AD11 astrocytes, can be partly rescued in vitro and in vivo by exogenous NGF addition. Altogether, our results demonstrate a causal link between NGF signaling and proper proliferation and differentiation of neural stem cells from the SVZ.

The Leitmotive of my dissertation is the role that the networks of relations existing among economic agents play in their behavior and, thus, in economic outcomes. While networks play a crucial role on many dimensions, one of the most prominent and investigated features is that they are privileged channels of information diffusion. The first and second chapter of this thesis explore instances where social networks are information channels. They both belong to the stream of network literature focusing on links at the individual level and their relevance with respect to labor outcomes. The first chapter focuses on the hiring stage and the potential wage differential imputable to being hired through social networks. The chapter develops a theoretical framework that takes into account the effects of moral hazard concerns and the diversity of networks and cultures on the choice of hiring channels. This model rationalizes the emergence of either informal or formal hiring channels and of either positive or negative wage differentials for workers hired through informal channels, depending on circumstances. In particular, the prevalent way of perceiving the use of networks as hiring channel is determinant. Indeed, a worker hired through a personal contact may either feel indebted and grateful or, on the contrary, she may think that she is somehow favored and does not really need to exert as much effort as the other workers. Conditional on being employed, in contexts where favoritism is prevalent, social networks are likely to be adopted as hiring channels for unskilled jobs and to result in wage penalties and even more, the stronger the ties. In contexts where gratitude predominates, however, the opposite happens. The empirical analysis is based on firm and individual matched data from the 2003 Investment Climate Assessment survey of the World Bank on Senegal's manufacturing formal sector. It estimates an endogenous switching model, allowing for both endogenous selection and switching effects of formal and informal hiring channels. The results for Senegal are consistent with the theoretical predictions in case of favoritism: informal hiring channels are preferred to fill unskilled vacancies and are associated with a wage penalty. Moreover, the probability of having been hired through a social network and the absolute value of wage penalties are increasing in the strength of ties. The second chapter focuses on the role played by networks during the career progression, independently of the hiring channel. It takes into account multiple mechanisms whereby networks have an impact on career outcomes and their dynamic coevolution. Indeed, professional links affect salary not only directly if they are valuable to the employer, but also indirectly through mobility since they represent privileged channels of information diffusion about job opportunities. Moreover, professional links have an impact on labor outcomes, but at the same time a worker's network is substantially shaped by career choices. The chapter develops therefore a dynamic framework where the utility of workers is affected by the characteristics of their professional network and by the mobility decisions they make during their career. The optimal value depends on professional networks directly through current utility to the extent that links are valuable to the employer and indirectly through the effect that they have on mobility decisions. The empirical analysis is based on individual and firm matched information provided by BoardEx Ltd, a UK supplier of data to headhunting companies, describing the career history of thousands of Executives in US, UK, France, and Germany. The data support the main hypotheses of the theoretical setting and the insight that professional networks are relevant both because they are valuable for the employer and because they facilitate job mobility. These findings are robust to alternative definitions of career value and specifications accounting for mobility and link endogeneity. We also find that contemporaneous colleagues are not a useful component of a worker's network. Moreover, networks characterized on average by ties between nodes that have been colleagues for a long time have a lower direct and indirect effect on labor outcomes. Finally, networks where many links are represented by workers that have been colleagues a long time before are less valuable to the employer. The third chapter investigates the relations between organizations and suggests that they may provide them with commitment ability. It models risky projects with autocorrelated productivity shocks as creating an option value of investing over time so that later investments benefit from the information revealed by the realization of earlier investments. However, once a firm has invested in a production project, lobbies within it (e.g., some divisions of the firm may have divergent interests from those of the Head Office or Board of Directors) or outside it (e.g., there may be political pressure as well as pressure from upstream or downstream trading partners) may pressurize into paying out early revenues from such investments precisely when the autocorrelation of productivity implies the firm should be reinvesting them in the project. An alliance with one or more other firms characterized by joint ownership of a production project may then provide a commitment mechanism against lobbies' pressure and therefore enable more efficient levels of investment. The same argument applies when decision makers are governments instead of firms, as often the case for infrastructure projects in developing countries. The Business Environment and Enterprises Performance survey data corroborate the model's prediction that organizations under conditions favorable to internal or external lobbying pressure are more likely than other firms to choose joint ventures, a common form of joint ownership, as their corporate governance structure. Moreover, the estimation of an instrumental variable probit model suggests that this effect is actually downward biased, consistently with the theoretical model. Indeed, although joint ventures are more necessary when a firm is under potential lobbying pressure, they also contribute to reducing such pressure. In conclusion, the three chapters of this thesis explore some instances where networks are key to economics, contributing to the shift from atomistic explanations toward a more relational understanding of economic phenomena.

AIM Early intervention programmes based on the manipulation of the extra-uterine environment have been used in preterm infants with the aim of improving development and functional outcome. Infant massage, among them, has proved effective for weight gain and reduced length of stay in the neonatal intensive care unit. We have recently shown that infant massage accelerates brainmaturation of low-risk preterm infants without brain abnormalities as measured by global parameters of electroencephalography (EEG) activity. In the present study we further analyse the same cohort of preterminfants, testing the hypothesis thatmassage determines changes in EEG spectral activity, a highly sensitive index of brainmaturation. METHOD Infants were randomly allocated to a massage or comparison group. Intervention consisted of standard care only (comparison group) or standard care plus infant massage (massage group).Massage was started at around 10 days after birth and was provided for 12 days during a 2-week period. EEG was performed at around 1 and 4 weeks, i.e. before and after intervention. Spectral EEG analysis was performed on 80 seconds of active sleep, applying the fast Fourier transform on the signal obtained from eight monopolar derivations. RESULTS The modification in global EEG spectral power between the two assessments was significantly different for the two groups, especially for the delta band activity; the spectral power did not change in massaged infants although, not surprisingly, it decreased significantly in the comparison group, as shown by previous studies. INTERPRETATION We propose thatmassage intervention affects the maturation of brain electrical activity and favours a processmore similar to that observed in utero in term infants.

Nerve growth factor (NGF) delivery to the brain of patients appears to be an emerging potential therapeutic approach to neurodegenerative disease, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracere-broventricular infusion and gene therapy. We previously showed that intranasal administration of NGF determined an amelioration of cholinergic deficit and a decrease in the number of phosphotau-positive neurons and of β-amyloid accumulation in AD11 mice, which express transgenic antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like neurodegeneration. In this study, we report that the Alzheimer-like neurodegeneration in AD11 mice is linked to progressive behavioral deficits in visual recognition memory and spatial memory starting from 4 months of age. To establish whether intranasal administration of NGF, started after the appearance of the first memory deficits, could revert the cognitive deficits in AD11 mice, we assessed the performance of NGF-treated or control AD11 mice in the object recognition test and in a test of memory for place and context. Deficits exhibited by untreated AD11 mice could be rescued by the intranasal administration of NGF. Thus, this route of administration provides a promising way to deliver NGF to the brain in a therapeutic perspective.

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.

The disruption of the nerve growth factor (NGF) gene in transgenic mice leads to a lethal phenotype (Crowley et al., 1994) and hinders the study of NGF functions in the adult. In this study the phenotypic knockout of NGF in adult mice was achieved by expressing transgenic anti-NGF antibodies, under the control of the human cytomegalovirus promoter. In adult mice, antibody levels are 2000-fold higher than in newborns. Classical NGF targets, including sympathetic and sensory neurons, are severely affected. In the CNS, basal forebrain and hippocampal cholinergic neurons are not affected in the early postnatal period, whereas they are greatly reduced in the adult (55 and 62% reduction, respectively). Adult mice show a reduced ability in spatial learning behavioral tasks. Adult, but not neonatal, transgenic mice further show a new phenotype at the level of peripheral tissues, such as apoptosis in the spleen and dystrophy of skeletal muscles. The analysis of this novel comprehensive transgenic model settles the controversial issue regarding the NGF dependence of cholinergic neurons in adult animals and reveals new NGF functions in adult non-neuronal tissues. The results demonstrate that the decreased availability of NGF in the adult causes phenotypic effects via processes that are at least partially distinct from early developmental effects of NGF deprivation.

Exogenous supply of nerve growth factor (NGF) prevents the effects of monocular deprivation. This suggests that visual afferents may be competing for an endogenous neurotrophic factor, related to NGF, whose production by postsynaptic cells depends on the activity of afferent fibers. To test the hypothesis that endogenous NGF may play a role in the functional and anatomical development of the rat geniculo cortical system, the physiological action of NGF in the rat visual system was antagonized by using two independent monoclonal antibodies which neutralize NGF (alpha D11 and 4C8). To provide a continuous supply of antibodies during the period of visual cortical plasticity, alpha D11 or 4C8 antibody-producing hybridoma cells were implanted in the lateral ventricle of rats at postnatal day 15. This resulted in dramatic alterations of two of the most important parameters characterizing the functional development of the visual system, namely, visual acuity and binocularity of cortical neurons and in shrinkage of cells in the lateral geniculate nucleus. This demonstrates that the action of endogenous NGF is necessary for the normal functional and anatomical development of the geniculocortical system.

Neural plasticity in the visual cortex, as tested by changes in its functional organization induced by monocular deprivation (MD), is present only during a restricted period of postnatal development (critical period). To investigate whether this process of synapse strengthening depends upon NGF, we antagonized endogenous NGF during the critical period by implanting anti-NGF producing cells. Anti-NGF treated and control rats were monocularly deprived after the end of the critical period. In anti-NGF treated but not in control rats MD was still effective. We conclude that antagonism of endogenous NGF prolongs the critical period, possibly by delaying the process of synapse consolidation in the visual cortex.

1. In seventy-six penetrations through areas 17 and 18 of the cat, neurones were regularly sampled at intervals of 100 micrometers and preferred orientation, optimal spatial frequency and resolving power were determined for each neurone in response to drifting sinusoidal gratings. 2. As already shown for area 17, in tangential penetrations through area 18, whenever the preferred orientation rotates progressively from cell to cell, the optimal spatial frequency tends to remain constant. 3. A statistical analysis on 1574 cells in areas 17 and 18 showed that for pairs of cells separated 200-300 micrometers along a track the difference in preferred orientation delta alpha and the difference in optimal spatial frequency delta f are not randomly distributed: cell pairs with small delta alpha are most likely to have large delta f and vice versa. 4. These findings indicate that in areas 17 and 18 neurones with the same optimal frequency are aligned along a direction orthogonal to the orientation columns. 5. The optimal spatial frequency, resolving power and the velocity cut-off were averaged for cells from different penetrations located in the same cortical layer or sublayer of area 18: mean optimal spatial frequency and acuity are highest in layer IV and lowest in layers II and V, while the velocity cut-off is highest in layers II and V and lowest in layer IV. 6. Our data suggest that the layering of cells according to optimal spatial frequency is a more subtle subdivision than the six histological layers.