Selective role for striatal and prefrontal regions in processing first trial feedback during single-trial associative learning.

Discrete jumps in knowledge, as exemplified by single-trial learning, are critical to survival. Despite its importance, however, one-trial learning remains understudied. We sought to better understand the brain activity adaptations that track punctuated changes in associative knowledge by studying visual-motor associative learning with functional magnetic resonance imaging. Human and primate neurophysiological studies of feedback-based learning indicate that performance feedback elicits high activity at first that diminishes rapidly with repeated success. Based on these findings we hypothesized a network of brain regions would track the importance of feedback, which is large early in learning and diminishes thereafter. Specifically, based on neurophysiological findings, we predicted that frontal and striatal regions would show a large activation to first trial feedback and a subsequent reduction selective to performance feedback but not stimulus cue presentation. We observed that the striatum and frontal cortex as well as several other cortical and subcortical sites exhibited this pattern. These findings match our prediction for activity in frontal and striatal regions. Furthermore, these observations support the more general hypothesis that a large network of regions participates in the associative process once the behavioral goal is definitively identified by first trial performance feedback. Activity in this network declines upon further rehearsal but only for feedback presentation. We suggest that, based on the timing of this process, these regions participate in binding together stimulus cue, motor response, and performance feedback information into an association that is used to accurately perform the task on after the first trial.

Transgenic mice expressing Na+-K+-ATPase in smooth muscle decreases blood pressure.

The Na(+)-K(+)-ATPase (NKA) is a transmembrane protein that sets and maintains the electrochemical gradient by extruding three Na(+) in exchange for two K(+). An important physiological role proposed for vascular smooth muscle NKA is the regulation of blood pressure via modulation of vascular smooth muscle contractility (5). To investigate the relations between the level of NKA in smooth muscle and blood pressure, we developed mice carrying a transgene for either the NKA alpha(1)- or alpha(2)-isoform (alpha(1 sm+) or alpha(2 sm+) mice) driven by the smooth muscle-specific alpha-actin promoter SMP8. Interestingly, both alpha-isoforms, the one contained in the transgene and the one not contained, were increased to a similar degree at both protein and mRNA levels. The total alpha-isoform protein was increased from 1.5-fold (alpha(1 sm+) mice) to 7-fold (alpha(2 sm+) mice). The increase in total NKA alpha-isoform protein was accompanied by a 2.5-fold increase in NKA activity in alpha(2 sm+) gastric antrum. Immunocytochemistry of the alpha(1)- and alpha(2)-isoforms in alpha(2 sm+) aortic smooth muscle cells indicated that alpha-isoform distributions were similar to those shown in wild-type cells. alpha(2 sm+) Mice (high expression) were hypotensive (109.9 +/- 1.6 vs. 121.3 +/- 1.4 mmHg; n = 13 and 11, respectively), whereas alpha(1 sm+) mice (low expression) were normotensive (122.7 +/- 2.5 vs. 117.4 +/- 2.3; n = 11 or 12). alpha(2 sm+) Aorta, but not alpha(1 sm+) aorta, relaxed faster from a KCl-induced contraction than wild-type aorta. Our results show that smooth muscle displays unique coordinate expression of the alpha-isoforms. Increasing smooth muscle NKA decreases blood pressure and is dependent on the degree of increased alpha-isoform expression.