Striatal injury induces overall brain alteration at the pallial, thalamic, and cerebellar levels

SIMPLE SUMMARY: Magnetic resonance imaging showed that striatal injury leads to structural changes within several brain areas. Here, we specify these changes via gene expression of synaptic plasticity markers, neuronal markers, assessing the number of newborn cells as well as cell densities. We found that the injury resulted in long-lasting modifications involving plasticity and neural protection mechanisms in areas directly as well as indirectly connected with the damaged striatum, including the cerebellum. ABSTRACT: The striatal region Area X plays an important role during song learning, sequencing, and variability in songbirds. A previous study revealed that neurotoxic damage within Area X results in micro and macrostructural changes across the entire brain, including the downstream dorsal thalamus and both the upstream pallial nucleus HVC (proper name) and the deep cerebellar nuclei (DCN). Here, we specify these changes on cellular and gene expression levels. We found decreased cell density in the thalamic and cerebellar areas and HVC, but it was not related to neuronal loss. On the contrary, perineuronal nets (PNNs) in HVC increased for up to 2 months post-lesion, suggesting their protecting role. The synaptic plasticity marker Forkhead box protein P2 (FoxP2) showed a bi-phasic increase at 8 days and 3 months post-lesion, indicating a massive synaptic rebuilding. The later increase in HVC was associated with the increased number of new neurons. These data suggest that the damage in the striatal vocal nucleus induces cellular and gene expression alterations in both the efferent and afferent destinations. These changes may be long-lasting and involve plasticity and neural protection mechanisms in the areas directly connected to the injury site and also to distant areas, such as the cerebellum

The power of using functional fMRI on small rodents to study brain pharmacology and disease

Functional Magnetic Resonance Imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anaesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically-induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest (ROIs). In addition, fMRI techniques allow one to dissect how specific modifications (e.g. treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations