Neuroscience
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Obstructive sleep apnea patients face episodes of chronic intermittent hypoxia (CIH), which has been suggested as a causative factor for increased sympathetic activity (SNA) and hypertension. Female rats exposed to CIH develop hypertension and exhibit changes in respiratory-sympathetic coupling, marked by an increase in the inspiratory modulation of SNA. We tested the hypothesis that enhanced inspiratory-modulation of SNA is dependent on carotid bodies (CBs) and are associated with changes in respiratory network activity. ⋯ Post-inspiratory neurons are active for a longer period during expiration in CIH-female rats. Further, using the computational model of a brainstem respiratory-sympathetic network, we demonstrate that a reduction in Pre-I/I neuron firing frequency simulates the enhanced inspiratory SNA modulation in CIH-female rats. We conclude that changes in respiratory-sympathetic coupling in CIH-female rats is dependent on CBs and it is associated with changes in firing properties of specific respiratory neurons types.
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Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an auditory stimulus drives reorganization of primary auditory cortex (A1), and the magnitude of this VNS-dependent plasticity is dependent on the stimulation parameters, including intensity and pulse rate. However, there is currently little data to guide the selection of VNS train durations, an easily adjusted parameter that could influence the effect of VNS-based therapies. Here, we tested the effect of varying the duration of the VNS train on the extent of VNS-dependent cortical plasticity. ⋯ Trains lasting 0.125 or 2.0 s failed to alter A1 responses, indicating that both shorter and longer stimulation durations are less effective at enhancing plasticity. A second set of experiments evaluating the effect of delivering 4 or 64 pulses in a fixed 0.5 s VNS train duration paired with tone presentation reveal that both slower and faster stimulation rates are less effective at enhancing plasticity. We incorporated these results with previous findings describing the effect of stimulation parameters on VNS-dependent plasticity and activation of neuromodulatory networks to generate a model of synaptic activation by VNS.
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Conductive hearing loss is a prevalent condition globally. It remains unclear whether conductive hearing loss that occurs during early development disrupts auditory peripheral systems. In this study, a mouse model of conductive auditory deprivation (CAD) was achieved using external auditory canal closure on postnatal day 12, which marks the onset of external ear canal opening. ⋯ Positive 8-hydroxy-2'-deoxyguanosine signals were noted in cochlear hair cells in the long-term group, suggesting that long-term auditory deprivation could disrupt auditory maturation via mitochondrial damage in cochlear hair cells. Conversely, no significant changes in cellular morphology were observed in cochlear hair cells and spiral ganglion cells in either short- or long-term groups. Collectively, our findings suggest that long-term conductive hearing deprivation during early stages of auditory development can cause significant and irreversible disruption that persists into adulthood.
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Previous work from our lab revealed that adult female rats have increased levels of myelin basic protein (MBP), a marker for myelination, in the orbitofrontal cortex (OFC) as compared to adult males. The goal of the present study was to determine the role of gonadal hormones, acting either in adulthood or at puberty, in the development of an adult sex difference in OFC levels of MBP. In an initial experiment, we replicated our previous results demonstrating that gonadally intact female rats have increased levels of MBP in the OFC as compared to males. ⋯ This reduction eliminated the sex difference in adult MBP levels in the OFC. These results reveal puberty to be an organizational time point for a sex difference in the OFC of adult rats in levels of a marker of myelination. This neuroanatomical difference may contribute to observed sex differences in OFC-associated behaviors including in inhibitory control.
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A secondary consequence of spinal cord injury (SCI) is debilitating chronic neuropathic pain, which is commonly morphine resistant and inadequately managed by current treatment options. Consequently, new pain management therapies are desperately needed. We previously reported that dopamine D3 receptor (D3R) dysfunction was associated with opioid resistance and increases in D1 receptor (D1R) protein expression in the spinal cord. ⋯ Following SCI, morphine + pramipexole and morphine + SCH 39166 significantly increased both thermal and mechanical thresholds. Morphine alone induced conditioned place preference, but when combined with either the D3R agonist or D1R antagonist preference was not induced. The data suggest that adjunct therapy with receptor-specific dopamine modulators can restore morphine analgesia and decrease reward potential and thus, represents a new target for pain management therapy after SCI.