Neuroscience
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Neurons in the auditory system are spatially organized in their responses to pure tones, and this tonotopy is expected to predict neuronal responses to more complex sounds such as vocalizations. We presented vocalizations with low-, medium- and high-frequency content to determine if selectivity of neurons in the inferior colliculus (IC) of mice respects the tonotopic spatial structure. Tonotopy in the IC predicts that neurons located in dorsal regions should only respond to low-frequency vocalizations and only neurons located in ventral regions should respond to high-frequency vocalizations. ⋯ We then used a nonlinear model of signal transduction in the cochlea that generates distortion products to predict neural responses to the vocalizations. We found that these predictions more closely matched the actual neural responses. Our findings suggest that the cochlea distorts the frequency representation in vocalizations and some neurons use this distorted representation to encode the vocalizations.
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Psychostimulant reward, as assessed via the conditioned place preference (CPP) paradigm, exhibits a daily rhythm with peaks in the late dark and early light periods, and a nadir near the light-to-dark transition. While this diurnal rhythm is correlated with neural activity in several corticolimbic structures, the brain regions mediating this behavioral rhythm remain unknown. Here, we examine the role of the ventral medial prefrontal cortex (mPFC). ⋯ Inactivation of the ventral mPFC at either of these phases also eliminated the daily rhythm in amphetamine-induced CPP via an increase in drug-paired chamber dwell time at the baseline nadir. Together, these results indicate that the ventral mPFC plays a critical role in mediating the diurnal rhythm in amphetamine CPP during both the acquisition and expression of learned reward-context associations. Moreover, as the loss of rhythmicity occurs via an increase at the nadir point, these results suggest that excitatory output from the ventral mPFC normally inhibits context-elicited reward seeking prior to the light-to-dark transition.
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Functional interactions between dopaminergic and noradrenergic systems occur in many brain areas, including the prefrontal cortex (PFC). Biochemical, electrophysiological and behavioral data indicate crosstalk between D1 dopamine receptor (D1R) and α1-adrenergic receptor (α1AR) signaling in the PFC. However, it is unknown whether these interactions occur within the same neurons, or between neurons expressing either receptor. ⋯ Our data also showed that the ratio of plasma membrane-bound to intracellular α1ARs is significantly reduced in D1R-expressing dendrites. Similar results were obtained using either a pan-α1AR or a selective α1bAR antibody to label noradrenergic receptors. Thus, these results demonstrate that D1Rs and α1ARs co-localize in PFC dendrites, thereby suggesting that the catecholaminergic effects on PFC function may be driven, at least in part, by cell-autonomous D1R-α1AR interactions.
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The majority of work examining the nucleus accumbens core (NAc) has focused on functions pertaining to behaviors guided by appetitive outcomes. These studies have pointed to the NAc as being critical for motivating behavior toward desirable outcomes. ⋯ To address this issue we asked if NAc lesions impact performance on a two-way active avoidance task in which rats must learn to shuttle back and forth in a behavioral training box in order to avoid a footshock predicted by an auditory tone. Although bilateral NAc lesions initially impaired reward-guided decision-making, we found that the same lesions improved acquisition and retention of two-way active avoidance.
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Numerous epidemiological studies have shown an association between pesticide exposure and the increased risk of developing Parkinson's disease. Previously we have reported that Dichlorvos exposure can induce oxidative stress, resulting in over-expression of pro-apoptotic genes and finally caspase-dependent nigrostriatal dopaminergic neuronal cell death in rat brain. Here, we examined the effect of caspase inhibition on PC12 cell death induced by Dichlorvos (30 μM). ⋯ Subsequent release of the apoptosis-inducing factor (AIF) from mitochondria and its translocation into the nucleus was also prevented by PJ34 pretreatment. In conclusion, the results of the present study show that caspase inhibition without concurrent inhibition of PARP1 is unlikely to be effective in preventing cell death because in the presence of the caspase inhibitor, caspase-independent cell death predominates due to PARP activation. These results suggest that combined therapeutic strategies directed at multiple cell death pathways may provide superior neuroprotection than those directed at a single mechanism.