Neuroscience
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Sandhoff disease (SD) is a lysosomal storage disorder characterized by the absence of hydrolytic enzyme β-N-acetylhexosaminidase (Hex), which results in storage of GM2 ganglioside in neurons and unremitting neurodegeneration. Neuron loss initially affects fine motor skills, but rapidly progresses to loss of all body faculties, a vegetative state, and death by five years of age in humans. A well-established feline model of SD allows characterization of the disease in a large animal model and provides a means to test the safety and efficacy of therapeutic interventions before initiating clinical trials. ⋯ SD cats were treated with intracranial delivery of adeno-associated viral (AAV) vectors expressing feline Hex, with a study endpoint 16weeks post treatment. AAV-mediated gene delivery repressed the expansion and activation of microglia and normalized MHC-II and MIP-1α levels. These data reiterate the profound inflammatory response in SD and show that neuroinflammation is abrogated after AAV-mediated restoration of enzymatic activity.
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Lateral habenula (LHb) is important for emotional processing. It is a link node between forebrain and midbrain. LHb is reciprocally connected with ventral tegmental area, acting as a regulatory center for the dopaminergic system. ⋯ In addition, the effects of LHb dopamine receptor activation and inactivation on aversive learning and memory were assessed. Our results showed that: (1) activation and inhibition of D1R but not D2R in LHb increased anxiety-like behavior but decreased depressive-like behavior in rats. (2) D1R activation and inactivation in LHb impaired aversive memory acquisition but not consolidation in rats, D1R agonist also impaired aversive memory retrieval in rats. These results might provide new clues about how LHb was involved in emotional processing.
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Previous studies yielded evidence for an interaction between age and valence in numerous cognitive processes. But, to date, no research has been conducted in the field of motor skills. In this study, we examined the age-related differences in the organization of an emotionally goal-directed locomotion task. ⋯ The fastest RTs were found in younger adults when faced with pleasant pictures, suggesting that older people may focus either on intermediate or final goals, depending on their value of pleasantness, and prioritize positive goals. We also found that the spatial coding of locomotion (trajectory and final body position) was affected in the same way by the valence of the intermediate goal in both age groups. Taken together, these findings provide new perspectives regarding the potential role of the emotional valence of the intermediate and final goals on the cognitive processes involved in action coding, such as in mental representations of action in older adults.
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The paraventricular nucleus of the thalamus (PVT) has been implicated in behavioral responses to reward-associated cues. However, the precise role of the PVT in these behaviors has been difficult to ascertain since Pavlovian-conditioned cues can act as both predictive and incentive stimuli. The "sign-tracker/goal-tracker" rat model has allowed us to further elucidate the role of the PVT in cue-motivated behaviors, identifying this structure as a critical component of the neural circuitry underlying individual variation in the propensity to attribute incentive salience to reward cues. ⋯ Presentation of a predictive stimulus that had been attributed with incentive value elicited c-Fos in PVT afferents from the lateral hypothalamus, medial amygdala (MeA), and the prelimbic cortex (PrL), as well as posterior PVT efferents to the NAc. PVT afferents from the PrL also showed elevated c-Fos levels following presentation of a predictive stimulus alone. Thus, presentation of an incentive stimulus results in engagement of subcortical brain regions; supporting a role for the hypothalamic-thalamic-striatal axis, as well as the MeA, in mediating responses to incentive stimuli; whereas activity in the PrL to PVT pathway appears to play a role in processing the predictive qualities of reward-paired stimuli.
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Blast exposure can cause tinnitus and hearing impairment by damaging the auditory periphery and direct impact to the brain, which trigger neural plasticity in both auditory and non-auditory centers. However, the underlying neurophysiological mechanisms of blast-induced tinnitus are still unknown. ⋯ We also observed an increased bursting rate in the low-frequency region at one month after blast exposure and in all frequency regions at three months after exposure. Taken together, spontaneous firing and bursting activity in the AC played an important role in blast-induced chronic tinnitus as opposed to acute tinnitus, thus favoring a bottom-up mechanism.