Contributions of signaling by dopamine neurons in dorsal striatum to cognitive behaviors corresponding to those observed in Parkinson's disease.

Although the cardinal features of Parkinson's disease (PD) are motor symptoms, PD also causes cognitive deficits including cognitive flexibility and working memory, which are strongly associated with prefrontal cortex (PFC) functions. Yet, early stage PD is not characterized by pathology in the PFC but by a loss of dopaminergic (DA) projections from the substantia nigra to the dorsal striatum. Moreover, the degree to which PD symptoms can be ascribed to the loss of DA alone or to the loss of DA neurons is unknown. We addressed these issues by comparing mouse models of either chronic DA depletion or loss of DA projections to the dorsal striatum. We achieved equal levels of striatal DA reduction in both models which ranged from mild (~25%) to moderate (~60%). Both models displayed DA concentration-dependent reductions of motor function as well as mild deficits of cognitive flexibility and working memory. Interestingly, whereas both motor function and cognitive flexibility were more severely impaired after mild ablation of DA neurons as compared to mild loss of DA alone, both models had equal deficits after moderate loss of DA. Our results confirm contributions of nigro-striatal dopamine signaling to cognitive behaviors that are affected in early stage PD. Furthermore, our findings suggest that the phenotype after ablation of DA neurons accrues from factors beyond the mere loss of DA.

Yeasts Induce Acetaldehyde Production in Wine Micro-oxygenation Treatments.

Micro-oxygenation (Mox) is a common technique used to stabilize color and reduce harsh astringency in red wines. Here, we investigate the role of residual sugars, phenolics, SO2, and yeast on the oxidation of wine in three studies. In a Mox experiment, populations of yeasts emerged after the loss of SO2, and this was associated with sharp increases in oxygen consumption and acetaldehyde production. No acetaldehyde production was observed without the presence of yeast. In an oxygen saturation experiment, unfiltered wines, in particular those with residual sugar >3 g/L, consumed oxygen more quickly and produced more acetaldehyde than filtered wines. In a final experiment, the reincorporation of oxygen and glucose immediately after the completion of fermentation of an otherwise dry synthetic wine resulted in significant acetaldehyde production. These experiments highlighted the importance of yeast metabolism in determining a wine's response to Mox and suggested that the role of chemical oxidation to produce acetaldehyde during Mox may not be very important. It appears that control of microbial populations and residual sugar levels may be key to managing Mox treatments in winemaking, and production scale experiments should be conducted.

Loss of glutamate signaling from the thalamus to dorsal striatum impairs motor function and slows the execution of learned behaviors.

Parkinson's disease (PD) is primarily associated with the degeneration of midbrain dopamine neurons, but it is now appreciated that pathological processes like Lewy-body inclusions and cell loss affect several other brain regions, including the central lateral (CL) and centromedian/parafascicular (CM/PF) thalamic regions. These thalamic glutamatergic neurons provide a non-cortical excitatory input to the dorsal striatum, a major projection field of dopamine neurons. To determine how thalamostriatal signaling may contribute to cognitive and motor abnormalities found in PD, we used a viral vector approach to generate mice with loss of thalamostriatal glutamate signaling specifically restricted to the dorsal striatum (CAV2Cre-Slc17a6lox/lox mice). We measured motor function and behaviors corresponding to cognitive domains (visuospatial function, attention, executive function, and working memory) affected in PD. CAV2Cre-Slc17a6lox/lox mice were impaired in motor coordination tasks such as the rotarod and beam-walk tests compared with controls (CAV2Cre-Slc17a6+/+ mice). They did not demonstrate much cognitive impairment in the Morris water maze or a water U-maze, but had slower processing reaction times in those tests and in a two-way active avoidance task. These mice could model an aspect of bradyphrenia, the slowness of thought that is often seen in patients with PD and other neurological disorders.

Restoration of dopamine signaling to the dorsal striatum is sufficient for aspects of active maternal behavior in female mice.

Striatal dopamine (DA) is important for motivated behaviors, including maternal behavior. Recent evidence linking the dorsal striatum with goal-directed behavior suggests that DA signaling in the dorsal striatum, not just the nucleus accumbens, could be involved in maternal behavior. To investigate this question, we tested the maternal behavior of mice with DA genetically restricted to the dorsal striatum. These mice had a mild deficit in pup retrieval but had normal licking/grooming and nursing behavior; consequently, pups were weaned successfully. We also tested a separate group of mice with severely depleted DA in all striatal areas. They had severe deficits in pup retrieval and licking/grooming behavior, whereas nursing behavior was left intact; again, pups survived to weaning at normal rates. We conclude that DA signaling in the striatum is a part of the circuitry mediating maternal behavior and is specifically relevant for active, but not passive, maternal behaviors. In addition, DA in the dorsal striatum is sufficient to allow for active maternal behavior.