Neuroscience
-
Brain-derived neurotrophic factor (BDNF) is known to mediate activity-dependent changes in the developing auditory system. Its expression in the brainstem auditory nuclei, auditory cortex and hippocampus of neonatal chicks (Gallus gallus domesticus) in response to in ovo high intensity sound exposure at 110 dB (arrhythmic sound: recorded traffic noise, 30-3000 Hz with peak at 2700 Hz, rhythmic sound: sitar music, 100-4000 Hz) was examined to understand the previously reported altered volume and neuronal number in these regions. In the brainstem auditory nuclei, no mature BDNF, but proBDNF at the protein level was detected, and no change in its levels was observed after in ovo sound stimulation (music and noise). ⋯ Expression microarray analysis was performed to understand changes in gene expression in the hippocampus in response to music and noise, followed by gene ontology analysis showing enrichment of probable signaling pathways. Differentially expressed genes like CAMK1 and STAT1 were found to be involved in downstream signaling on comparing music versus noise-exposed chicks. In conclusion, we report that BDNF is differentially regulated in the auditory cortex at the transcriptional and post-translational level, and in the hippocampus at the post-translational level in response to in ovo sound stimulation.
-
Concussion injury results in a rapid onset of transient neurological impairment that can resolve quickly, or sometimes evolve over time, but usually resolve within seven to 10 days. However, a small but noticeable cohort (~10%) of individuals continues to experience persistent lingering effects, particularly fatigue, recognized as post-concussion symptoms (PCS). This study explored neurophysiological mechanisms in people with persistent PCS. ⋯ Somatosensory differences were observed for amplitude discrimination (F2,57 = 5.166; p = 0.009), temporal order judgment (F2,57 = 4.606; p = 0.014) and duration discrimination (F2,57 = 6.081; p = 0.004). Increased intracortical inhibition in TMS single pulse suprathreshold stimulation (110%: F2,57 = 6.842; p = 0.002; 130%: F2,57 = 4.900; p = 0.011; 150%: F2,57 = 4.638; p = 0.014; 170%: F2,57 = 9.845; p < 0.001) and paired pulse protocols was also seen (SICI: F2,57 = 23.390; p < 0.001, and LICI: F2,57 = 21.603; p < 0.001). Using non-invasive stimulation techniques, this novel study showed increased cortical inhibition and compromised central information processing, suggesting neural mechanisms underpinning ongoing fatigue, allowing for potential clinical rehabilitation strategies.
-
Locomotion involves complex combinations of translational and rotational head movements. For gaze stability, this necessitates the interplay of angular and linear vestibulo-ocular reflexes (VOR) as well as the integration of visual feedback about the desired viewing distance. Furthermore, gaze stabilizing systems must be able to cope with vast differences in head motion brought about by changing locomotor speeds and patterns (walking vs. running). ⋯ Thus, horizontal and vertical gaze stabilization strategies appear to be considerably different. Whereas horizontal gaze control is likely governed by passive sensorimotor reflexes throughout all locomotor speeds, vertical gaze stabilization switches to an automated feed-forward control at faster locomotion. This switch is presumably driven by efference copies from spinal locomotor commands that were previously shown to govern gaze stabilization in animal models during stereotypic locomotion.
-
Tinnitus is thought to be triggered by aberrant neural activity in the central auditory pathway and is often accompanied by comorbidities of emotional distress and anxiety, which imply maladaptive functional connectivity to limbic structures, such as the amygdala and hippocampus. Tinnitus patients with normal audiograms can also have accompanying anxiety and depression, clinically. To test the role of functional connectivity between the central auditory pathway and limbic structures in patients with tinnitus with normal audiograms, we developed a murine noise-induced tinnitus model with a temporary threshold shift (TTS). ⋯ We found increased fMRI responses with amplitude of low-frequency fluctuation (ALFF) in the auditory cortex and decreased ALFF in the amygdala and hippocampus at day 1, but decreased ALFF in the auditory cortex and increased ALFF in the amygdala at day 28 post-noise exposure in tinnitus mice. Decreased functional connectivity between auditory brain regions and limbic structures was demonstrated at day 28 in tinnitus mice. Therefore, aberrant neural activities in tinnitus mice with TTS involved not only the central auditory pathway, but also limbic structures, and there was maladaptive functional connectivity between the central auditory pathway and limbic structures, such as the amygdala and hippocampus.
-
The expression of potassium ion channel subunit 1.2 (Kv1.2) in the dorsal root ganglion (DRG) influences the excitability of neurons, which contributes to the induction and development of neuropathic pain (NPP); however, the molecular mechanisms underlying the downregulation of Kv1.2 in NPP remain unknown. Histone deacetylase (HDAC) inhibitors are reported to attenuate the development of pain hypersensitivity in rats with NPP. Whether HDAC inhibitors contribute to regulation of Kv1.2 expression, and which specific HDAC subunit is involved in NPP, remain unexplored. ⋯ Furthermore, treatment with HDAC2, but not HDAC1, siRNA also relieved mechanical and thermal hypersensitivity and upregulated the Kv1.2 expression in this model. In vitro transfection of PC12 cells with HDAC2 and HDAC1 siRNA confirmed that only HDAC2 siRNA could regulate the expression of Kv1.2. These findings suggest that HDAC2, but not HDAC1, is involved in NPP through regulation of Kv1.2 expression.