Neuroscience
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The intrinsic value of an action refers to the inherent sense that experiencing a behavior is enjoyable even if it has no explicit outcome. Previous research has suggested that a common valuation mechanism within the reward network may be responsible for processing the intrinsic value of achieving both the outcome and external rewards. However, how the intrinsic value of action is neurally represented remains unknown. ⋯ The results showed that the stopwatch game with the action-outcome contingency evoked a greater degree of enjoyment because the participants chose this condition over those that lacked such a contingency. The ventral striatum and midbrain were activated only when action-outcome contingency was present. Thus, the intrinsic value of action was represented by an increase in ventral striatal and midbrain activation.
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Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. ⋯ Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.
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The mechanism of action of botulinum neurotoxin type A (BoNT/A) is well characterized, but some published evidence suggests the potential for neuronal retrograde transport and cell-to-cell transfer (transcytosis) under certain experimental conditions. The present study evaluated the potential for these processes using a highly selective antibody for the BoNT/A-cleaved substrate (SNAP25197) combined with 3-dimensional imaging. SNAP25197 was characterized in a rat motor neuron (MN) pathway following toxin intramuscular injections at various doses to determine whether SNAP25197 is confined to MNs or also found in neighboring cells or nerve fibers within spinal cord (SC). ⋯ Therefore, under the present experimental conditions, our results suggest that BoNT/A is confined to MNs and any evidence of distal activity is due to limited systemic spread of the toxin at higher doses and not through transcytosis within SC. Lastly, at higher doses of BoNT/A, SNAP25197 was expressed throughout MNs and colocalized with synaptic markers on the plasma membrane at 6 days post-treatment. These data support previous studies suggesting that SNAP25197 may be incorporated into SNARE-protein complexes within the affected MNs.
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Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. ⋯ At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway.
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Huntington's disease (HD) is a hereditary neurodegenerative disorder resulting from N-terminal polyglutamine expansion in the huntingtin protein. A relatively selective and early loss of medium spiny neurons in the striatum is a hallmark of HD neuropathology. Although the exact mechanism of mutant huntingtin-mediated neurodegeneration is unclear, recent evidence suggests that NMDA-receptor-mediated excitotoxicity is involved. ⋯ Our findings demonstrate that deletion of a single allele of p35 in the B6 YAC128 mice results in an upregulation of Akt activity, and increases phosphorylation of mutant huntingtin at Ser421. Longitudinal behavioral analysis showed that this 50% reduction in p35 and p25 levels did not improve accelerating Rotarod performance in these YAC128 mice. However, a complete deletion of p35 normalized the accelerating Rotarod performance relative to their non-transgenic littermates at four months of age.