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T Pizzorusso

Publications and source records attributed to T Pizzorusso.

31 records · Page 2Linked to original sources
PubMed1997

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

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

Animals↗
PubMed1996

The visual response of retinal ganglion cells is not altered by optic nerve transection in transgenic mice overexpressing Bcl-2.

Attempts to rescue retinal ganglion cells from retrograde degeneration have had limited success, and the residual function of surviving neurons is not known. Recently, it has been found that axotomized retinal ganglion cells die by apoptotic mechanisms. We have used adult transgenic mice overexpressing the Bcl-2 protein, a powerful inhibitor of apoptosis, as a model for preventing injury-induced cell death in vivo. Several months after axotomy, the majority of retinal ganglion cells survived and exhibited normal visual responses. In control wild-type mice, the vast majority of axotomized retinal ganglion cells degenerated, and the physiological responses were abolished. These results suggest that strategies aimed at increasing Bcl-2 expression, or mimicking its function, might effectively counteract trauma-induced cell death in the central nervous system. Neuronal survival is a necessary condition in the challenge for promoting regeneration and eventually restoring neuronal function.

Animals↗
PubMed1996

Plasticity in the developing visual system.

A long series of studies beginning with the pioneering experiments of Wiesel and Hubel [1] has shown that correct visual experience is crucial for the development of the visual system. Recent results suggest that neurotrophic factors of the nerve growth factor family might have a relevant role in mediating the effects of visual experience on the developing visual system.

Animals↗
PubMed1995

A developmentally regulated nerve growth factor-induced gene, VGF, is expressed in geniculocortical afferents during synaptogenesis.

The expression of the nerve growth factor-inducible gene VGF has been examined by in situ hybridization. Western blot and immunohistochemical studies in the developing and adult rat central nervous system, with particular emphasis on the visual system. Both the messenger RNA and the protein are particularly abundant in the developing dorsal lateral geniculate nucleus, appearing, respectively, at embryonal day 16 and 18. After its onset at E16, VGF messenger RNA expression increases progressively in the dorsal lateral geniculate nucleus and remains high during the first two post-natal weeks; afterwards, it gradually decreases and, at the offset of the plasticity period, it reaches very low levels maintained in adulthood. A similar time course has been observed for VGF protein in the dorsal lateral geniculate nucleus area, by semi-quantitative Western blots. In addition to the presence of the protein in the geniculate neurons, a strong, transient immunoreactivity has been found at the embryonic cortical subplate at E18, reflecting the presence of the antigen in axonal terminals originating from thalamic neurons. Interestingly, we found that the blockade of afferent electrical activity by intraocular injection of tetrodotoxin strongly reduces the level of VGF messenger RNA in the dorsal lateral geniculate nucleus. Although the function of the VGF protein is not known, it had been previously proposed that VGF could be a precursor for neuropeptide/s. The spatiotemporal expression of VGF, together with the observation of a regulation by electrical activity, suggest that this protein may be relevant in the process of synaptogenesis and/or synaptic stabilization in the developing geniculocortical connections.

Afferent Pathways↗
PubMed1995

Monocular deprivation decreases the expression of messenger RNA for brain-derived neurotrophic factor in the rat visual cortex.

We found that deprivation of pattern vision in one eye, that leaves luminance detection performance unaffected, is sufficient to reduce brain-derived neurotrophic factor (but not trkB) messenger RNA in the visual cortex of young and adult rats. Monocular deprivation by means of eyelids' suture was performed during or after the critical period and the cortical amount of brain-derived neurotrophic factor messenger RNA was analysed by in situ hybridization and RNAase protection after 15-30 days of deprivation. A reduction of brain-derived neurotrophic factor messenger RNA was observed in the visual cortex contralateral to the deprived eye in rats monocularly deprived during the critical period. The same reduction was also found in rats monocularly deprived after the end of the critical period, when anatomical or physiological signs of monocular deprivation are absent. The pharmacological blockade of retinal activity equally affected the expression of brain-derived neurotrophic factor messenger RNA in young and adults. Quantitative RNAase protection assays revealed that the cortical level of brain-derived neurotrophic factor messenger RNA was reduced to the same extent when intraocular injections of tetrodotoxin were performed within or after the critical period. A developmental study of brain-derived neurotrophic factor messenger RNA expression in rat visual cortex showed a marked increase around the time of natural eye-opening followed by a plateau from postnatal day 20 until adult age. Messenger RNA for the kinasic domain of brain-derived neurotrophic factor receptor (trkB) was found in the dorsal lateral geniculate nucleus and the visual cortex during development and in adults. Our results suggest that the reduction of brain-derived neurotrophic factor messenger RNA induced by monocular deprivation is related to the absence of pattern vision rather than to the competitive interactions that underlie the effects of monocular deprivation during the critical period.

Age Factors↗
PubMed1995

Characterization of NMDA receptor subunit-specific antibodies: distribution of NR2A and NR2B receptor subunits in rat brain and ontogenic profile in the cerebellum.

Selective antisera for NMDA receptor subunits NR2A and NR2B have been developed. Each antiserum identifies a single band on an immunoblot at approximately 175 kDa that appears to be the appropriate subunit of the NMDA receptor. Using these antisera the relative densities of the subunits in eight areas of adult rat brain have been determined. The NR2A subunit was found to be at its highest level in hippocampus and cerebral cortex, to be at intermediate levels in striatum, olfactory tubercle, mid-brain, olfactory bulb, and cerebellum, and to be at lowest levels in the pons-medulla. The NR2B subunit was found to be expressed at its highest levels in the olfactory tubercle, hippocampus, olfactory bulb, and cerebral cortex. Intermediate levels were expressed in striatum and mid-brain, and low levels were detected in the pons-medulla. No signal for NR2B was found in the cerebellum. These regional distributions were compared with that for [3H]MK-801 binding sites. It was found that although the distribution of the NR2A subunit corresponds well with radioligand binding, the distribution of the NR2B subunit does not. The ontogenic profiles of NR2A and NR2B subunits in the rat cerebellum were also determined. Just following birth [postnatal day (P) 2] NR2A subunits are undetectable, whereas NR2B subunits are expressed at amounts easily measurable. Beginning at about P12 the levels of NR2A rise rapidly to reach adult levels by P22. At the same time (P12), levels of NR2B protein begin to decline rapidly to reach undetectable levels by 22 days after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Schwann cells transplanted in the lateral ventricles prevent the functional and anatomical effects of monocular deprivation in the rat.

We investigated whether the transplant of Schwann cells prevents the physiological and morphological effects of monocular deprivation in the rat. On the day of eye opening in rats (postnatal day 14), we transplanted Schwann cells in the lateral ventricles and sutured the eyelids of one eye. After 20-30 days, at the end of the critical period for the visual system development, we analyzed the functional properties of visual cortical neurons. Spontaneous discharge, orientation selectivity, and receptive field size of visual cortical neurons in transplanted animals were in the normal range. Transplantation of Schwann cells prevented the detrimental effects of monocular deprivation on ocular dominance and binocularity of cortical neurons. Visual acuity of the deprived eye estimated by visually evoked potentials was also normal. Schwann cells derived from adult animals were as effective as those derived from neonates. The effects of Schwann cells on monocular deprivation were dependent upon the number of cells present in the transplant so that 10(6) Schwann cells were sufficient to prevent the effect of monocular deprivation, whereas 10(5) and 3.3 x 10(5) Schwann cells were ineffective, and 6.3 x 10(5) cells gave variable results. Shrinkage of the deprived lateral geniculate neurons was prevented by a transplant of 10(6) cells. In rats transplanted with hybridoma cells producing an antibody that functionally blocks nerve growth factor (NGF), we found that the effect of cotransplanted Schwann cells on monocular deprivation was partly counteracted. We conclude that transplantation of Schwann cells prevents both functional and anatomical effects of monocular deprivation, presumably acting through the production of NGF. We propose that transplants of Schwann cells could be a promising technique for clinical applications.

Animals↗
PubMed1994

Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system.

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.

Animals↗
PubMed1994

Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation.

Postnatal development of rat visual cortical functions was studied by recording extracellularly from the primary visual cortex of 22 animals ranging in age from postnatal day 17 (P17) to P45. We found that in the youngest animals (P17-P19) all visual cortical functions tested were immature. Selectivity for orientation and movement direction of visual stimuli was almost absent, most cells received binocular input and their mean receptive field size was 5-6 times the adult size. Visual acuity was half its adult value. These functional properties developed gradually during the following weeks and by P45 they were all adult-like. This functional development is affected by manipulations of the visual input such as dark rearing (DR) and monocular deprivation (MD). DR prevented the normal postnatal maturation of visual cortical functions: in P60 rats, dark reared from birth, their visual cortical functions resembled those of P19-P21 rats. MD from P15 to P45 resulted in a dramatic shift of the ocular dominance distribution (ODD) in favour of the open eye and in a loss of visual acuity for the deprived eye. To determine the sensitive period of rat visual cortex to MD (critical period) we evaluated the shift in ODD of visual cortical neurones in rats that were subjected to the progressive delay of the onset of fixed MD period (10 days). Our results show that the critical period begins around the end of the third postnatal week, peaks between the fourth and fifth week and starts to decline from the end of the fifth week.

Age Factors↗
PubMed1993

Monocular deprivation effects in the rat visual cortex and lateral geniculate nucleus are prevented by nerve growth factor (NGF). I. Visual cortex.

The effects of monocular deprivation done during the critical period are usually ascribed to competition between the two sets of monocular thalamic afferents taking place at cortical level. We have suggested that loss in competition for the deprived eye is explained by the lack of a neurotrophic factor, produced in the cortex and dependent on electrical activity. To test this hypothesis we have exogenously supplied nerve growth factor (NGF) to rats monocularly deprived (MD) during the critical period, and studied whether monocular deprivation still affected the functional and anatomical organization of the visual cortex. NGF is produced in the rat visual cortex during the critical period, and its expression, at least in the hippocampus, seems to be regulated by electrical activity. Ocular dominance distribution of area 17 neurons, visual acuity, and Parvalbumin immunoreactivity (Parva-LI) were determined in four sets of animals: normal rats, control untreated monocularly deprived rats, deprived rats treated with cytochrome c (to control for non-specific aspects of NGF treatment), and deprived rats treated with NGF. Parva-LI is an excellent marker for the effects of monocular deprivation on the functional organization of the rat visual cortex. We found that exogenous supply of NGF completely prevented the shift in ocular dominance distribution of visual cortical neurons, the loss of visual acuity for the deprived eye, and the strong reduction in Parva-LI induced by monocular deprivation in control rats.

Acetylcholinesterase↗
PubMed1992

Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats.

The hypothesis that NGF could play a role in the plasticity of the developing mammalian visual cortex was tested in monocularly deprived (MD) rats. In particular, we have asked whether an exogenous supply of NGF could prevent the changes in ocular dominance distribution induced by monocular deprivation. Hooded rats were monocularly deprived for 1 month, starting at postnatal day 14 (P14), immediately before eye opening, by means of eyelid suture. In eight rats, only monocular deprivation was performed; in eight rats, monocular deprivation was combined with intraventricular injections of beta-NGF, and in three rats, with intraventricular injections of cytochrome C. Injections (2 microliters) were given every other day for a period of 1 month. Single neuron activity was recorded in the primary visual cortex of MD rats, MD rats treated with NGF, and MD rats treated with cytochrome C at the end of the deprivation period, and in normal rats of the same age. We found that monocular deprivation caused a striking change in the ocular dominance distribution of untreated MD rats, reducing binocular cells by a factor of two and increasing by a factor of eight the number of cells dominated by the nondeprived eye. In MD NGF-treated rats, the ocular dominance distribution was indistinguishable from the normal. Cytochrome C treatment was completely ineffective in preventing the ocular dominance shift induced by monocular deprivation. To test whether NGF affected cortical physiology or interfered with transmission of visual information, we evaluated in NGF-treated rats the spontaneous discharge and the orientation selectivity. We found these functional properties to be in the normal range. We conclude that NGF is effective in preventing the effects of monocular deprivation in the rat visual cortex and suggest that NGF is a crucial factor in the competitive processes leading to the stabilization of functional geniculocortical connections during the critical period.

Animals↗
PubMedDate not supplied

Vision in mice with neuronal redundancy due to inhibition of developmental cell death.

Transgenic mice overexpressing bcl-2, due to inhibition of naturally occurring cell death, have much larger brains and optic nerves as compared to wild-type mice. Since developmental cell death is believed to exert a crucial role in establishing the mature neural circuitry and function, we asked the question of whether basic aspects of vision were altered in bcl-2 mice. Local visually evoked potentials (VEPs) in response to patterned stimuli were recorded from the primary visual cortex. The representation of the vertical meridian was displaced by about 15% in the bcl-2 mouse, accounting for brain expansion. However, visual acuity, contrast threshold, and response latency were normal, indicating that compensatory mechanisms can ensure normal basic properties of vision in spite of marked neuronal redundancy.

Animals↗