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A decrease in brain-derived neurotrophic factor (BDNF), a neurotrophin essential for synaptic function, plasticity and neuronal survival, is evident early in the progression of Alzheimer’s disease (AD), being apparent in subjects with mild cognitive impairment or mild AD, and both proBDNF and mature BDNF levels are positively correlated with cognitive measures. BDNF delivery is, therefore, considered of great interest as a potentially useful therapeutic strategy to contrast AD. Invasive BDNF administration has indeed been recently used in animal models of AD with promising results in rescuing memory deficits, synaptic density and cell loss. Here, we tested whether non-invasive intranasal administration of different BDNF concentrations after the onset of cognitive and anatomical deficits (6 months of age) could rescue neuropathological and memory deficits in AD11 mice, a model of NGF deprivation-induced neurodegeneration. In addition to AD hallmarks, we investigated BDNF effects on microglia presence in the brain of AD11 mice, since alterations in microglia activation have been associated with ageing-related cognitive decline and with the progression of neurodegenerative diseases, including AD. We found that intranasal delivery of 42 pmol BDNF (1 μM), but not PBS, was sufficient to completely rescue performance of AD11 mice both in the object recognition test and in the object context test. No further improvement was obtained with 420 pmol (10 μM) BDNF dose. The strong improvement in memory performance in BDNF-treated mice was not accompanied by an amelioration of AD-like pathology, Aβ burden, tau hyperphosphorylation and cholinergic deficit, but there was a dramatic decrease of CD11b immunoreactive brain microglia. These results reinforce the potential therapeutic uses of BDNF in AD and the non-invasive intranasal route as an effective delivery strategy of BDNF to the brain. They also strengthen the connection between neuroinflammation and neurodegenerative dementia and suggest microglia as a possible mediator of BDNF therapeutic actions in the brain.

Environmental enrichment (EE) is known to profoundly affect the central nervous system (CNS) at the functional, anatomical and molecular level, both during the critical period and during adulthood. Recent studies focusing on the visual system have shown that these effects are associated with the recruitment of previously unsuspected neural plasticity processes. At early stages of brain development, EE triggers a marked acceleration in the maturation of the visual system, with maternal behaviour acting as a fundamental mediator of the enriched experience in both the foetus and the newborn. In adult brain, EE enhances plasticity in the cerebral cortex, allowing the recovery of visual functions in amblyopic animals. The molecular substrate of the effects of EE on brain plasticity is multi-factorial, with reduced intracerebral inhibition, enhanced neurotrophin expression and epigenetic changes at the level of chromatin structure. These findings shed new light on the potential of EE as a non-invasive strategy to ameliorate deficits in the development of the CNS and to treat neurological disorders.

Pattern VEPs have been recorded locally from the binocular portion of the primary visual cortex of wild type- and different transgenic mice by means of microelectrodes. Local pattern VEPs have been used on the one hand to obtain information on basic cortical layout (topography, laminar analysis) and ocularity (relative contribution of the contralateral and ipsilateral eye), and on the other hand to evaluate several aspects of visual physiology that have a counterpart in visual behavior (visual acuity, contrast sensitivity, motion sensitivity, response latency). As compared to visual behavior, pattern VEPs offer the advantage that several aspects of vision can be evaluated in the same animals, including those with poor behavior due to motor- or cognitive deficits, even during the postnatal development. Pattern VEPs provide a means for characterizing the visual phenotype of mutant mice and for the evaluation of the effects induced by experimental manipulation.

Environmental enrichment potentiates neural plasticity, enhancing acquisition and consolidation of memory traces. In the sensory cortices, after cortical circuit maturation and sensory function acquisition are completed, neural plasticity declines and the critical period 'closes'. In the visual cortex, this process can be prevented by dark-rearing, and here we show that environmental enrichment can promote physiological maturation and consolidation of visual cortical connections in dark-reared rats, leading to critical period closure.

We have investigated the effectiveness of embryonal tectal tissue transplants in preserving the physiological activity of lesioned ganglion cells by recording the visual responses from the adult rat retina after section of the optic nerve, with or without transplants of embryonal nervous tissue on the stump. We have found that transplant of embryonal nervous tissue at the level of the optic nerve section has dramatic effects in preserving visual retinal responses to patterned stimuli for times as long as five months after surgery. By this time retinal responses to patterned stimuli have almost completely disappeared in control animals with optic nerve section alone.

Development of visual acuity is known to be impaired by early monocular deprivation. This may be due to lack of visual experience or to abnormal binocular competition. We report here the results of behavioural experiments on monocularly deprived kittens in which the optic chiasm had been split. In these kittens it has been found that visual acuity of the deprived eye is as good as the visual acuity of the non-deprived eye, namely 2-2.5 c/deg.

Review of a series of experiments which demonstrate that surgical deafferentation of proprioceptive fibers of the Vth cranial nerve affects various visual performances of cats.

Dichoptic presentation of patterns similar in shape but of very different contrast results in the perception of only the high contrast pattern (binocular suppression). When recording from binocular neurons of the cat visual cortex, we have found an effect which is strikingly similar to this perceptual phenomenon. If a high and a low contrast grating are presented simultaneously, one to each eye, the cell's response to the low contrast stimulus is suppressed.

After intracranial transection of the optic nerve in cats the retinal stump of the nerve was injected with HRP. Surviving retinal ganglion cells can be retrogradely labeled at least up to 15.5 months of postoperative survival.

We investigated the effects of unilateral deafferentation of extraocular proprioception on the orienting behaviour of cats. The ophthalmic branch of the Vth cranial nerve, in which most of the extraocular proprioceptive fibers are known to run, was cut unilaterally in adult cats. The animals had been previously trained to jump from a start box to a luminous target at various possible locations in the right or left visual hemifield. The postsurgical orienting performance of the animals, evaluated from the difference between landing position and position of the target, differed from the presurgical performance. The postsurgical errors were typically: (1) ipsiversive to the side of the section, (2) usually of a larger magnitude in the hemifield contralateral to the section, (3) present in binocular as well as in monocular viewing conditions and approximately of the same magnitude for jumps guided by either eye. These findings indicate that extraocular proprioception plays a role in the orienting behaviour of cats.

Electroretinographic responses (ERG) to homogeneous light flashes and to alternating gratings were recorded from either eye of monkeys in which one optic nerve had been previously sectioned. Three weeks after optic nerve section the ERG response of the operated eye to alternating gratings was drastically reduced in amplitude and 5 weeks after surgery it was reduced to noise level. The uniform field ERG was unaffected. Histological examination of whole-mounted retinas of monkeys sacrificed 6 and 8 weeks after optic nerve section showed a loss of ganglion cells in the operated eye. It is concluded that the integrity of ganglion cells is essential for the generation of a normal ERG response to gratings.

Previous experiments have shown that the ERG response to alternating gratings vanishes gradually within 4 months after transection of the optic nerve, changes begin after 2-3 weeks. The response to gratings of low spatial frequencies deteriorates earlier than the response to gratings of high spatial frequencies (Maffei and Fiorentini 1981). Quantitative analysis of ganglion cell sizes in retinal wholemounts shows that ganglion cell shrinkage and ganglion cell loss begin at three weeks in the periphery of the retina, particularly in the temporal retina. The same morphological alteration subsequently becomes apparent also in the area centralis and the nasal retina, respectively. The main and early cell loss occurs among medium sized ganglion cells, supposedly the beta-cells. Among the alpha-cells only shrinkage is observed up to two months postoperatively. Light- and electron microscopic examination of cross sections through the retina show that pathological changes are restricted to the innermost layers.