On whether the environmental enrichment may provide cognitive and brain reserves.

The construct of brain and cognitive reserves holds that cognitive enrichment fosters the development of neuroplasticity properties, which permit normal cognitive functioning even in the presence of brain pathology. Interpreting the experience-dependent increase of neuronal connectivity and efficiency in the light of the reserve theory provides an interesting approach for explaining the maintenance of cognitive function observed in some subjects affected by neurodegenerative disorders. In fact, mental and physical engagement with complex environments strengthens synaptic connectivity and provides the means by which preexisting neuronal networks are efficiently utilized and alternative networks are recruited to meet environmental demands and to cope with brain damage. There is considerable interest in determining the biological factors that allow the development of these reserves. To investigate these factors, it is possible to model situations of environmental enrichment in animals that parallel human cognitive enrichment. Experimental findings indicate that early onset and extended housing in an environment with enhanced sensorimotor, cognitive, and social stimulations results in significant changes in brain biochemistry, synaptic connectivity, and neuronal function in enriched animals. These changes provide the groundwork for the improvement of behavioral performance and maintenance of performance following brain damage. As this is the fundamental assumption of the reserve hypothesis, it is possible that as human educational attainment and occupational status, environmental enrichment develops reserves to be spent in the case of a subsequent lesion.

Layer and regional effects of environmental enrichment on the pyramidal neuron morphology of the rat.

The environmental enrichment (EE) paradigm is widely used to study experience-dependent brain plasticity. Several studies have investigated functional and anatomical EE effects. However, as EE effects are different according to cerebral region, cortical layer, dendritic field and morphological index considered, a univocal characterization of neuronal morphological changes following rearing in enriched environments is lacking. Aim of the present study was to characterize in the rat the effects of EE on the neuronal morphology of frontal and parietal cortical regions, the main target areas of the stimulation provided by the paradigm. Male Wistar rats were housed in an enriched environment for 3.5 months from the 21st postnatal day. For the morphological analysis, biotinylated dextran amine (BDA)-labeled pyramidal neurons were selected from frontal (M1-M2) and parietal (S1-S2) cortical layers III and V. Apical and basal dendritic branching and spines were analyzed using the Sholl method. Results showed that EE increased branching and spines in both layers of frontal cortex, but had a greater effect on apical arborization. In parietal cortex, EE significantly affected branching and spines in layer III but not layer V neurons, in which only a tendency to be influenced by the rearing conditions was observed in basal arborization. It is hypothesized that these multifaceted morphological EE effects are connected to the heavy involvement of a sensory-motor circuit engaged in the guidance of voluntary action and in motor learning activated by EE stimulation.

Environmental enrichment provides a cognitive reserve to be spent in the case of brain lesion.

To experimentally verify the reserve hypothesis, the influence of rearing conditions on the cognitive performances and on dendritic spines following basal forebrain lesions was analyzed. Adult rats reared in enriched or standard conditions were depleted of the cholinergic projection to the neocortex by 192 IgG-saporin injection into Ch4 region of basal forebrain. Their performance in spatial tasks was compared with that of intact animals reared in analogous conditions. Furthermore, number and density of dendritic spines of the layer-III parietal pyramidal neurons were analyzed. Cholinergic depletion of forebrain cortex resulted in impaired performances in most behavioral tasks in animals reared in standard conditions. Conversely, the enriched lesioned animals did not exhibit most deficits evoked by cholinergic lesion, even if some deficits, such as perseverative behaviors, were still present. The pyramidal neurons exhibited an increased spine number and density in the lesioned animals reared in standard conditions. In the enriched lesioned animals, the enhancement of spine number and density elicited by the rearing condition was fully maintained but not further increased in the presence of the lesion. Thus, rearing in an enriched environment results in the development of brain and cognitive reserves that reduce the cognitive impairment following forebrain lesions.

Is the cerebellum involved in the visuo-locomotor associative learning?

The role played by cerebellar circuits in visuo-motor associative learning is still unclear. The aim of the present study was to analyse cerebellar involvement using a visuo-locomotor associative learning paradigm that did not require spatial competences. Hemicerebellectomized (HCbed) and Control rats were tested in a visual discrimination task. First, both groups of rats had to learn that a reward was associated with an object that had a specific colour and shape (Experiment 1). Then, the shape but not the colour of the rewarded object was modified to verify whether the animals were able to transfer the rule of rewarding or whether they had to acquire a new association (Experiment 2). In the first sessions of the Experiment 1, HCbed animals displayed a tendency toward peripheral circling and a delay of about three sessions in reaching the criterion of correct choices compared to Controls. This delay has to be correlated to the need to overcome the procedural impairment elicited by the HCb. Once the HCbed animals put efficient procedural abilities into action, they exhibited a similar increase in percentages of successes from the fourth session onward as Controls. The results of Experiment 2 confirm the intact associative abilities of HCbed animals, as demonstrated by their progressive increase in successful associative responses, which, at the end of the transfer phase, were not significantly different from those of the Control group. The present findings indicate that the presence of a cerebellar lesion delays but does not prevent visuo-locomotor associative learning and that stimulus generalisation is performed without difficulty even in the presence of a cerebellar lesion.

Cerebellar damage impairs detection of somatosensory input changes. A somatosensory mismatch-negativity study.

Several recent studies support the view that the cerebellum's contribution to sensory processing is not limited to movement regulation. In a previous paper (Restuccia D, Valeriani M, Barba C, Le Pera D, Capecci M, Filippini V, Molinari M. Functional changes of the primary somatosensory cortex in patients with unilateral cerebellar lesions. Brain 2001; 124: 757-68) we showed that the cerebellum influences somatosensory input processing at very early stages. The present study was aimed at verifying whether an analogous influence is also exerted at higher levels. For some time it has been known that in the auditory modality a specific event-related potential (ERP), that is, mismatch negativity (MMN), reflects preattentive detection of changes in the incoming stimulus by comparing the new stimulus with sensory memory traces. To test the cerebellar influence on the processing of incoming somatosensory stimuli we first verified whether the electrical stimulation of fingers, according to an 'oddball' paradigm within a stimulus-ignored condition, was able to elicit event-related components specifically linked to the preattentive detection of change. We analysed scalp responses obtained from eight healthy volunteers during frequent and rare electrical stimulation of the first and fifth finger of the left hand, respectively. To ensure that responses to deviant stimuli were due to changes in detection mechanisms, rather than to activation of new afferents, we also analysed responses to rare stimulation alone ('standard-omitted' condition). The 'oddball' stimulation was able to elicit a parieto-occipital extra negativity that was different in scalp distribution and latency from the N140 response to the 'standard-omitted' stimulation. We considered that this response was related to changes in detection mechanisms and labelled it somatosensory mismatch negativity (S-MMN). When the same procedure was applied to six patients with unilateral cerebellar lesions we found that the S-MMN was clearly abnormal after stimulation of the affected hand (ipsilateral to the affected cerebellar hemisphere). Earlier ERPs, as well as ERPs elicited during the 'standard-omitted' condition, were fully normal. Present data indicate that cerebellar processing is involved in preattentive detection of somatosensory input changes. In conclusion, this study demonstrates the reliability of S-MMN recordings and indicates that subjects with cerebellar damage may be impaired in the cortical processing of incoming somatosensory inputs.

Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat.

An enriched environment consists of a combination of enhanced social relations, physical exercise and interactions with non-social stimuli that leads to behavioral and neuronal modifications. In the present study, we analyzed the behavioral effects of environmental complexity on different facets of spatial function, and we assessed dendritic arborisation and spine density in a cortical area mainly involved in the spatial learning, as the parietal cortex. Wistar rat pups (21 days old) were housed in enriched conditions (10 animals in a large cage with toys and a running wheel), or standard condition (two animals in a standard cage, without objects). At the age of 3 months, both groups were tested in the radial maze task and Morris water maze (MWM). Morphological analyses on layer-III pyramidal neurons of parietal cortex were performed in selected animals belonging to both experimental groups. In the radial maze task, enriched animals exhibited high performance levels, by exploiting procedural competencies and working memory abilities. Furthermore, when the requirements of the context changed, they promptly reorganized their strategies by shifting from prevalently using spatial procedures to applying mnesic competencies. In the Morris water maze, enriched animals more quickly acquired tuned navigational strategies. Environmental enrichment provoked increased dendritic arborisation as well as increased density of dendritic spines in layer-III parietal pyramidal neurons.