Highlights d Striatal low-threshold spiking interneurons (LTSIs) mediate goal-directed learning d Reward-associated LTSI Ca 2+ activity decreases with operant learning d Decreasing LTSI activity accelerates and increasing LTSI activity slows learning d Effects on learning are dependent on LTSI GABAergic signaling

Value-based decision making relies on distributed neural systems that weigh the benefits of actions against the cost required to obtain a given outcome. Perturbations of these systems are thought to underlie abnormalities in action selection seen across many neuropsychiatric disorders. Genetic tools in mice provide a promising opportunity to explore the cellular components of these systems and their molecular foundations. However, few tasks have been designed that robustly characterize how individual mice integrate differential reward benefits and cost in their selection of actions. Here we present a forced-choice, two-alternative task in which each option is associated with a specific reward outcome, and unique operant contingency. We employed global and individual trial measures to assess the choice patterns and behavioral flexibility of mice in response to differing "choice benefits" (modeled as varying reward magnitude ratios) and different modalities of "choice cost" (modeled as either increasing repetitive motor output to obtain reward or increased delay to reward delivery). We demonstrate that (1) mouse choice is highly sensitive to the relative benefit of outcomes; (2) choice costs are heavily discounted in environments with large discrepancies in relative reward; (3) divergent cost modalities are differentially integrated into action selection; (4) individual mouse sensitivity to reward benefit is correlated with sensitivity to reward costs. These paradigms reveal stable individual animal differences in value-based action selection, thereby providing a foundation for interrogating the neural circuit and molecular pathophysiology of goal-directed dysfunction.

Goal-directed behaviors are essential for normal function and significantly impaired in neuropsychiatric disorders. Despite extensive associations between genetic mutations and these disorders, the molecular contributions to goal-directed dysfunction remain unclear. We examined mice with constitutive and brain region-specific mutations in Neurexin1α, a neuropsychiatric disease-associated synaptic molecule, in value-based choice paradigms. We found Neurexin1α knockouts exhibited reduced selection of beneficial outcomes and impaired avoidance of costlier options. Reinforcement modeling suggested this was driven by deficits in updating and representation of value. Disruption of Neurexin1α within telencephalic excitatory projection neurons, but not thalamic neurons, recapitulated choice abnormalities of global Neurexin1α knockouts. Furthermore, this selective forebrain excitatory knockout of Neurexin1α perturbed value-modulated neural signals within striatum, a central node in feedback-based reinforcement learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in value-modulated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

The microstructure, elemental distribution and rheological behavior of two varieties of gari and their doughs (eba) were investigated. SEM analysis revealed a concave structure with fibre-strands, which were altered after processing to eba. Gari nanostructures which were analyzed with TEM were not affected when processed to eba. SEM-EDX microanalysis revealed the presence of magnesium, potassium, calcium, manganese, iron, and cobalt for both varieties, which were altered after processing. Rheological analysis revealed increases in storage modulus, with concomitant loss factor for both varieties. Their viscosity decreased with increasing shear rate. GC-MS analysis revealed the presence of sugar, fatty acids, and steroids in both varieties, which were also affected after processing. Both varieties showed significant free radical scavenging activity which was not affected after processing. These results indicate that the conclave microstructure, elements and phytochemicals of both gari varieties are altered after processing to eba, with their nanostructure and antioxidant activity unaltered.