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The mitochondrion is a double membrane structured organelle involved in a variety of regulatory functions such as calcium signaling, production of adenosine triphosphate, apoptosis, reactive oxygen species generation, cell growth, and cell cycling. Impaired mitochondrial function is evident in various neurological disorders stemming from both acute and chronic neural injury. Herein, we review the role of mitochondrial regulation in maintaining cellular homeostasis, the consequences of their dysfunction in relation to pathophysiology after neurotrauma, approaches being used to promote their bioenergetic integrity for neuroprotection, and multifaceted methods being used to preserve/rescue their function following both traumatic brain and spinal cord injury. Cerebral organoids are stem cell-derived, self-organizing three-dimensional cultures. Owing to the remarkable degree to which they recreate the cellular diversity observed in the human brain, they have attracted significant interest as a novel model system for research and drug development, as well as capturing the public imagination. However, many questions remain about the extent to which these cultures recapitulate neurodevelopment and the defining features of the human brain. To clarify the fidelity of human organoid models, Bhaduri and colleagues compared the molecular profile of brain organoid cells with that of primary cells from fetal brain. find more They observed that, whilst brain organoids broadly recapitulate the cellular profile of human brain, they lack the subtypes of cell classes seen in human brain. In addition, they showed marked expression of cellular stress markers, which could be reversed by transplanting organoid cells into neonatal mouse brain. The authors hypothesise that in vitro culture induces a cellular stress response and that it is this that impairs maturation. Thus, whilst their findings strike a note of caution in the use of organoids as a model for early human brain development, they lay a foundation for improving the accuracy of organoid models in the future. Cyclin-dependent kinase 5 (Cdk5) is a regulator of axon growth and radial neuronal migration in the developing mouse brain, and it plays critical roles in cortical structure formation and brain function. However, the function of Cdk5 in cortico-cortical and cortico-sensorimotor networks in the adult remains largely unknown. In this study, we investigated the function of Cdk5 in the rostral secondary motor cortex (M2) in the male mouse using CRISPR/Cas9 gene editing and somatic brain transgenesis, to produce M2-specific knockdown of Cdk5 in neurons in the male mouse. Mouse deficient in Cdk5 in the M2 exhibited a reduction in both the number of functional synapses and the total basal dendritic length, as well as motor dysfunction. Furthermore, whole-cell patch-clamp recordings in layer V green fluorescent protein (GFP)-tag pyramidal neurons revealed a decrease in the frequency and amplitude of miniature EPSCs and miniature IPSCs, as well as a reduction in the population synaptic responses (fEPSPs) in these mice. Specifically, retrograde labeling showed that Cdk5 knockdown in the M2 caused a reduction in long-range projections to the M2 from the thalamus/prefrontal cortex and claustrum. Collectively, our findings show a new regulatory role of Cdk5 in neural circuit maintenance, and that the changes in neural transmission and circuits in the mice with Cdk5 knockdown in the M2 likely contribute to the motor dysfunction in these animals. The main neuropathological hallmarks of Parkinson’s disease (PD) are loss of dopaminergic neurons in the substantia nigra and intraneuronal protein aggregates immunoreactive for α-synuclein phosphorylated at serine 129 (pS129). Most cases of PD are idiopathic; however, genetic mutations have been identified in several genes linked to familial PD. Mutations in the gene encoding α-synuclein are causally linked to dominantly inherited forms of PD and mutations in the PTEN-induced kinase-1 (PINK1) gene are linked to recessively inherited forms of PD. Because abnormal α-synuclein protein aggregates appear spontaneously in PINK1 knockout (KO) rats, we hypothesize that PINK1-deficiency causes endogenous α-synuclein to be more prone to aggregation. α-Synuclein aggregation does not normally occur in mice or rats, however, it can be induced by intracranial injection of α-synuclein pre-formed fibrils (PFFs), which also induces loss of dopaminergic nigral neurons 3-6 months post-injection. Because PINK1-deficiency is linked to early-onset PD, we further hypothesize that PINK1 KO rats will show earlier PFF-induced neurodegeneration compared to wild-type (WT) rats. Herein, we report that intracranial injection of α-synuclein PFFs into the dorsal striatum induced more abundant pS129 α-synuclein in PINK1 KO rat brains compared to WT littermate controls. Moreover, the synuclein extracted from the brains of PFF-injected PINK1 KO rats was more insoluble compared to PFF-injected WT littermates, suggesting greater progression of α-synuclein pathology in PINK1 KO rats. Four weeks post-injection, PFFs caused significant loss of dopaminergic neurons in the substantia nigra of PINK1 KO rats, but not WT controls. Together, our results indicate that PINK1 deficiency increases vulnerability to α-synuclein aggregation and dopaminergic neurodegeneration in vivo. Evidence suggests the hypothalamic-pituitary-adrenal (HPA) axis is involved in Alcohol Use Disorders (AUDs), which might be mediated by an imbalance of glucocorticoid receptor (GR), GRα and GRβ, activity. GRβ antagonizes the GRα isoform to cause glucocorticoid (GC) resistance. In the present study, we aimed to investigate the effects of chronic continuous free-choice access to ethanol on GR isoform expression in subregions of the mesocorticolimbic reward circuit. Adult male alcohol-preferring (P) rats had concurrent access to 15% and 30% ethanol solutions, with ad lib access to lab chow and water, for six weeks. Quantitative Real-time PCR (RT-PCR) analysis showed that chronic ethanol consumption reduced GRα expression in the nucleus accumbens shell (NAcsh) and hippocampus, whereas ethanol drinking reduced GRβ in the nucleus accumbens core (NAcc), prefrontal cortex (PFC), and hippocampus. An inhibitor of GRα, microRNA-124-3p (miR124-3p) was significantly higher in the NAcsh, and GC-induced gene, GILZ, as a measure of GC-responsiveness, was significantly lower.