Increases in GFAP immunoreactive astrocytes in the cerebellar molecular layer of young adult CBA/J mice

Background CBA/J mice are standard experimental animals in auditory studies, and age-related changes in auditory pathways are well documented. However, changes in locomotion-related brain regions have not been systematically explored. Results We showed an increase in immunoreactivity for glial fibrillary acidic protein (GFAP) in the cerebellar molecular layer associated with Purkinje cells in mice at 24 weeks of age but not in the younger mice. Increased GFAP immunoreactivity appeared in the form of clusters and distributed multifocally consistent with hyperplasia of astrocytes that were occasionally associated with Purkinje cell degeneration. Three out of 12 animals at 16 and 24 weeks of age exhibited pre-convulsive clinical signs. Two of these 3 animals also showed increased GFAP immunoreactivity in the cerebellum. Rotarod behavioral assessments indicated decreased performance at 24 weeks of age. Conclusions These results suggest minimal to mild reactive astrocytosis likely associated with Purkinje cell degeneration in the cerebellum at 24 weeks of age in CBA/J mice. These findings should be taken into consideration prior to using this mouse strain for studying neuroinflammation or aging.

Documented Lipid Per oxidative Intoxication of Cerebellar Molecular Cell Layer

Background: Cerebellar cortexconsists of three layers. The outer molecular, middlePurkinje cell layer, inner granule cell layer. Lithium the alkali metal hasdeleterious effects on nervous tissue and this study proved the injurious effects of lithium on molecular cell layer of cerebellum. Aim: To observe and report the damaging histological and morphological change of the decrement in the thickness of cerebellar molecular layer by Lithium. Methods: This study was designed to observe the microscopic changes of thickness of molecular layer in rat cerebellum. For this experimental study 12 animals were used, they were divided into two groups, each comprising of 6 animals. Results: Group-A received normal lab diet and water ad libitum while group B received injectable lithium carbonate 20 mg/kg/ for 4 weeksrespectively. Micrometry was done and changes of the thickness of molecular cell layer were recorded and documented. Conclusion: The pernicious effects of Lithium Carbonate on molecular cerebellar cortex were visualized and evaluated .Highly significantly decreased changes of thickness of molecular cell layer were documented in rat cerebellum. Keywords: Lipidperoxidation,Molecular cell layeratrophy, decomposition

Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo

Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions.

Molecular layer interneurons in the cerebellum encode for valence in associative learning

We used two-photon microscopy to study the role of ensembles of cerebellar molecular layer interneurons (MLIs) in a go-no go task where mice obtain a sugar water reward if they lick a spout in the presence of the rewarded odorant and avoid a time out when they refrain from licking for the unrewarded odorant. In naïve animals the MLI responses did not differ between the odorants. With learning, the rewarded odorant elicited a large increase in MLI calcium responses, and the identity of the odorant could be decoded from the differential response. Importantly, MLIs switched odorant responses when the valence of the stimuli was reversed. Finally, mice took a longer time to refrain from licking in the presence of the unrewarded odorant and had difficulty becoming proficient when MLIs were inhibited by chemogenetic intervention. Our findings support a role for MLIs in learning valence in the cerebellum.