Neuroscience
-
Stress is a contributing factor in the etiology of several mood and anxiety disorders, and social defeat models are used to investigate the biological basis of stress-related psychopathologies. Male Syrian hamsters are highly aggressive and territorial, but after social defeat they exhibit a conditioned defeat (CD) response which is characterized by increased submissive behavior and a failure to defend their home territory against a smaller, non-aggressive intruder. Hamsters with dominant social status show increased c-Fos expression in the infralimbic (IL) cortex following social defeat and display a reduced CD response at testing compared to subordinates and controls. ⋯ Furthermore, dominants display more c-Fos-positive cells in both the IL and PL, but not vHPC, compared to subordinates. These findings suggest that dominant hamsters selectively activate IL and PL, but not vHPC, projections to the amygdala during social defeat, which may be responsible for their reduced CD response. This project extends our understanding of the neural circuits underlying resistance to social stress, which is an important step toward delineating a circuit-based approach for the prevention and treatment of stress-related psychopathologies.
-
Pairing vagus nerve stimulation (VNS) with movements or sounds can direct robust plasticity in motor or auditory cortex, respectively. The degree of map plasticity is influenced by the intensity and pulse width of VNS, number of VNS-event pairings, and the interval between each pairing. It is likely that these parameters interact, influencing optimal implementation of VNS pairing protocols. ⋯ Increasing ISI (Dispersed VNS) did not lead to an enhancement of cortical plasticity. Reducing the current intensity and number of stimulations (Fast VNS) resulted in robust cortical plasticity, using 6 times fewer VNS pairings than the Standard protocol. These findings reveal an interaction between current intensity, stimulation number, and ISI and identify a novel VNS paradigm that is substantially more efficient than the previous standard paradigm.
-
Elevated levels of cholesterol (hypercholesterolemia) and homocysteine (hyperhomocysteinemia, HHcy) in blood have been linked with the pathology of Parkinson's disease. However, the impact of their combined effect on brain is unknown. The present study aims to investigate the effect of HHcy on dopaminergic neurons in brain of mice with hypercholesterolemia. ⋯ While neither hypercholesterolemia nor HHcy caused significant changes in the number of TH-positive neurons, hypercholesterolemia in combination with HHcy resulted in a significant loss of nigral TH-positive neurons. The results highlighted the involvement of mitochondrial complex-I dysfunction with subsequent generation of hydroxyl radicals for the observed loss of midbrain dopamine neurons in animals receiving the combined treatment. Thus, the findings of the present study pointed out the combined effect of homocysteine and cholesterol toward dopamine neuronal dysfunctions, which has substantial relevance to Parkinson's disease.
-
Changes in inhibition following traumatic brain injury (TBI) appear to be one of the major factors that contribute to excitation:inhibition imbalance. Neuron pathology, interneurons in particular evolves from minutes to weeks post injury and follows a complex time course. Previously, we showed that in the long-term in diffuse TBI (dTBI), there was select reduction of specific dendrite-targeting neurons in sensory cortex and hippocampus while in motor cortex there was up-regulation of specific dendrite-targeting neurons. ⋯ However, DG of hippocampus now showed reduction of dendrite-targeting inhibitory neurons. Finally, with respect to motor cortex, there was an upregulation of dendrite-targeting interneurons in the supragranular layers at 24 h returning to normal levels by 2 weeks. Overall, our findings reconfirm that dendritic inhibition is particularly susceptible to brain trauma, but also show that there are complex brain-area-specific changes in inhibitory neuronal numbers and in compensatory changes, rather than a simple monotonic progression of changes post-dTBI.
-
Maladaptive behavioral outcomes following stress have been associated with immune dysregulation. For example, we have previously reported that stress-induced dorsal hippocampal interleukin-1β signaling is critical to the development of stress-enhanced fear learning (SEFL). In parallel, astroglial signaling has been linked to the development of post-traumatic stress disorder (PTSD)-like phenotypes and our most recent studies have revealed astrocytes as the predominant cellular source of stress-induced IL-1β. ⋯ Subsequent experiments examined dorsal hippocampal astrocyte volume, surface area, and synaptic contacts (colocalization with postsynaptic density 95 (PSD95)) following exposure to severe stress (capable of inducing SEFL). While severe stress did not alter dorsal hippocampal astrocyte volume or surface area, the severe stressor exposure reduced dorsal hippocampal PSD95 immunoreactivity and the colocalization analysis showed reduced PSD95 colocalized with astrocytes. Collectively, these data provide evidence to support the functional efficacy of the glial-expressing DREADD employed, and suggest that an astrocyte-specific manipulation, activation of astroglial Gi signaling, is sufficient to protect against the development of SEFL, a PTSD-like behavior.