36 research outputs found
Enrichment from Birth Accelerates the Functional and Cellular Development of a Motor Control Area in the Mouse
BACKGROUND:There is strong evidence that sensory experience in early life has a profound influence on the development of sensory circuits. Very little is known, however, about the role of experience in the early development of striatal networks which regulate both motor and cognitive function. To address this, we have investigated the influence of early environmental enrichment on motor development. METHODOLOGY/PRINCIPAL FINDINGS:Mice were raised in standard or enriched housing from birth. For animals assessed as adults, half of the mice had their rearing condition reversed at weaning to enable the examination of the effects of pre- versus post-weaning enrichment. We found that exclusively pre-weaning enrichment significantly improved performance on the Morris water maze compared to non-enriched mice. The effects of early enrichment on the emergence of motor programs were assessed by performing behavioural tests at postnatal day 10. Enriched mice traversed a significantly larger region of the test arena in an open-field test and had improved swimming ability compared to non-enriched cohorts. A potential cellular correlate of these changes was investigated using Wisteria-floribunda agglutinin (WFA) staining to mark chondroitin-sulfate proteoglycans (CSPGs). We found that the previously reported transition of CSPG staining from striosome-associated clouds to matrix-associated perineuronal nets (PNNs) is accelerated in enriched mice. CONCLUSIONS/SIGNIFICANCE:This is the first demonstration that the early emergence of exploratory as well as coordinated movement is sensitive to experience. These behavioural changes are correlated with an acceleration of the emergence of striatal PNNs suggesting that they may consolidate the neural circuits underlying these behaviours. Finally, we confirm that pre-weaning experience can lead to life long changes in the learning ability of mice
Ten_m3 Regulates Eye-Specific Patterning in the Mammalian Visual Pathway and Is Required for Binocular Vision
Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision
Perineuronal Nets Play a Role in Regulating Striatal Function in the Mouse
The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse
Rapid Reversal of Chondroitin Sulfate Proteoglycan Associated Staining in Subcompartments of Mouse Neostriatum during the Emergence of Behaviour
BACKGROUND: The neostriatum, the mouse homologue of the primate caudate/putamen, is the input nucleus for the basal ganglia, receiving both cortical and dopaminergic input to each of its sub-compartments, the striosomes and matrix. The coordinated activation of corticostriatal pathways is considered vital for motor and cognitive abilities, yet the mechanisms which underlie the generation of these circuits are unknown. The early and specific targeting of striatal subcompartments by both corticostriatal and nigrostriatal terminals suggests activity-independent mechanisms, such as axon guidance cues, may play a role in this process. Candidates include the chondroitin sulfate proteoglycan (CSPG) family of glycoproteins which have roles not only in axon guidance, but also in the maturation and stability of neural circuits where they are expressed in lattice-like perineuronal nets (PNNs). METHODOLOGY/PRINCIPAL FINDINGS: The expression of CSPG-associated structures and PNNs with respect to neostriatal subcompartments has been examined qualitatively and quantitatively using double-labelling for Wisteria floribunda agglutinin (WFA), and the mu-opioid receptor (muOR), a marker for striosomes, at six postnatal ages in mice. We find that at the earliest ages (postnatal day (P)4 and P10), WFA-positive clusters overlap preferentially with the striosome compartment. By P14, these clusters disappear. In contrast, PNNs were first seen at P10 and continued to increase in density and spread throughout the caudate/putamen with maturation. Remarkably, the PNNs overlap almost exclusively with the neostriatal matrix. CONCLUSIONS/SIGNIFICANCE: This is the first description of a reversal in the distribution of CSPG associated structures, as well as the emergence and maintenance of PNNs in specific subcompartments of the neostriatum. These results suggest diverse roles for CSPGs in the formation of functional corticostriatal and nigrostriatal connectivity within the striosome and matrix compartments of the developing caudate/putamen
Early association between TH-positive striatonigral terminals and WFA staining dissipates after postnatal day 14.
<p>Panels show relationship between WFA binding (AβC) and tyrosine hydroxylase (TH) expression (DβF) at P4 (A, D, G), P10 (B, E, H) and P14 (C, F, I). (G, H, I) are merged channel images of the two corresponding images above. At P4, TH staining is seen in discrete patches. WFA clusters overlap well with these regions (A, D, G, arrows). At this age, TH-positive dopamine terminals correspond well with ΞΌOR-positive striosomes. By P10, TH staining has become considerably more uniform, especially in the medial regions of the neostriatum, than at P4, although some patches can still be observed dorsally. These remaining TH patches can be seen to overlap with WFA clusters (B, E, H, arrows). Arrowheads show PNNs starting to form in the dorsolateral striatum (B, H). By P14, TH staining is uniformly distributed in the entire neostriatum, when WFA staining is predominantly associated with PNNs in the neostriatal matrix (F). Arrows (F, I) mark WFA-poor areas which are reminiscent of striosomes. Scale bar: 600 ΞΌm.</p
The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment
PNN distribution is maintained at postnatal day 21.
<p>Conventions are the same as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003020#pone-0003020-g003" target="_blank">Fig 3</a>. (AβC): Rostral sections. (DβF): More caudal sections. (A, D): WFA staining. (B, E): ΞΌOR distribution. (C, F): merged. The emergent, selective expression of PNN in the matrix compartment, first observed at P14, as well as the generally higher degree of WFA staining in medial and dorsomedial extracellular matrix, is maintained at P21. Scale bar: 600 ΞΌm.</p
Removal of striatal PNNs improves Morris water maze acquisition.
<p>A significant interaction between treatment Group and training Days was observed in terms of latency to goal (Repeated measures ANOVA, group versus days interaction, <i>P</i>β=β0.013) (A). Closer analysis revealed that ChABC treated animals (red) took significantly shorter amounts of time to find the submerged platform on Days 2 and 4 (ANOVA, P<0.05). (B) Although both ChABC (red dotted) and vehicle (grey dotted) treated groups exhibited a preference for the quadrant that previously contained the submerged platform (Quadrant D; inset), no significant difference was observed between the two groups. (C) Sample hemispheres of ChABC (left) and saline (right) treated striatum from animals that had completed behavioral testing. PNNs remained digested even after two weeks of training. Scale bar: 1 mm.</p
WFA labels PNNs.
<p>(A): Low-power image showing distribution of WFA labelling in a coronal section from a P31 mouse brain. Punctate labelling is visible in the striatum as well as in cortex and other brain areas. Scale bar: 1 mm. (B): Higher power confocal image of the region outlined with red in A, showing that the punctate labelling form PNN like structures. Scale bar: 50 ΞΌm. (C, D): Sample PNNs imaged at high power with confocal microscopy, correspond to those marked in B. The net-like labelling (arrowheads) surrounding the soma and proximal dendrites, which is characteristic of PNNs, is visible. Scale bar: 20 ΞΌm.</p