Retinoic acid modulation of granule cell activity and spatial discrimination in the adult hippocampus.

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARß) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

Continuous long-range measurement of tonic dopamine with advanced FSCV for pharmacodynamic analysis of levodopa-induced dyskinesia in Parkinson's disease.

Levodopa, a dopamine prodrug, alleviates the motor symptoms of Parkinson's disease (PD), but its chronic use gives rise to levodopa-induced dyskinesia (LID). However, it remains unclear whether levodopa pharmacodynamics is altered during the progressive onset of LID. Using in vivo fast-scan cyclic voltammetry and second-derivative-based background drift removal, we continuously measured tonic dopamine levels using high temporal resolution recording over 1-h. Increases to tonic dopamine levels following acute levodopa administration were slow and marginal within the naïve PD model. However, these levels increased faster and higher in the LID model. Furthermore, we identified a strong positive correlation of dyskinetic behavior with the rate of dopamine increase, but much less with its cumulative level, at each time point. Here, we identified the altered signature of striatal DA dynamics underlying LID in PD using an advanced FSCV technique that demonstrates the long-range dynamics of tonic dopamine following drug administration.