Distinct dopaminergic control of the direct and indirect pathways in reward-based and avoidance learning behaviors.

The nucleus accumbens (NAc) plays a pivotal role in reward and aversive learning and learning flexibility. Outputs of the NAc are transmitted through two parallel routes termed the direct and indirect pathways and controlled by the dopamine (DA) neurotransmitter. To explore how reward-based and avoidance learning is controlled in the NAc of the mouse, we developed the reversible neurotransmission-blocking (RNB) technique, in which transmission of each pathway could be selectively and reversibly blocked by the pathway-specific expression of transmission-blocking tetanus toxin and the asymmetric RNB technique, in which one side of the NAc was blocked by the RNB technique and the other intact side was pharmacologically manipulated by a transmitter agonist or antagonist. Our studies demonstrated that the activation of D1 receptors in the direct pathway and the inactivation of D2 receptors in the indirect pathway are key determinants that distinctly control reward-based and avoidance learning, respectively. The D2 receptor inactivation is also critical for flexibility of reward learning. Furthermore, reward and aversive learning is regulated by a set of common downstream receptors and signaling cascades, all of which are involved in the induction of long-term potentiation at cortico-accumbens synapses of the two pathways. In this article, we review our studies that specify the regulatory mechanisms of each pathway in learning behavior and propose a mechanistic model to explain how dynamic DA modulation promotes selection of actions that achieve reward-seeking outcomes and avoid aversive ones. The biological significance of the network organization consisting of two parallel transmission pathways is also discussed from the point of effective and prompt selection of neural outcomes in the neural network.

MR imaging of Wallerian degeneration in the brainstem: temporal relationships.

Degeneration of the myelin sheath and axon distal to the most proximal site of axonal interruption secondary to axonal disease has been called wallerian degeneration. On MR imaging, wallerian degeneration of the pyramidal tract can be observed as an abnormal signal intensity, showing prolonged T1 and T2 relaxation times that correspond to the corticospinal tract, with or without shrinkage of the ipsilateral cerebral peduncle and pons. Review of MR studies in 150 cases of supratentorial cerebrovascular accidents showed abnormal signal alterations in the ipsilateral brainstem in 33 of the cases. Abnormal intensity in the ipsilateral brainstem was seen as early as 5 weeks after the supratentorial ictus and was fully evident after 10 weeks in all 33 cases. Signal alterations were strongest at about 3-6 months when compared with alterations seen at 10 weeks or even 10 months after the ictus. Shrinkage of the ipsilateral brainstem appeared as early as 8 months and was demonstrated in all cases 13 months after the ictus. MR seems to be the most effective technique for early detection of wallerian degeneration and may provide insight into its pathophysiological and chemical changes.

Hydroxyapatite-reactive salivary protein revealed by iso-electrofocusing electrophoresis.

Salivary protein involvement in the formation of acquired enamel pellicle, so far, has been discussed in terms of hydroxyapatite (HA)-reactive salivary proteins only from the parotid gland. This study was undertaken to seek this type of protein in the human whole (mixed) saliva and to investigate its normal and pathological variations. Several kinds of hydroxyapatite, either biogenous or synthesized by solid phase reaction, were used as a powder (250 mesh). HA was incubated with concentrated whole saliva at 25 degrees for 30 min. After centrifugation and filtration salivary proteins were analysed on a Multiphor isoelectrofocusing gel electrophoresis. The control salivary proteins were separated into three major groups; acidic (A1-A8), neutral neutral (N1-N4), and basic (B1-B3) isoelectric point (pI). In the HA incubated sample, one of the major neutral bands (NI) preferentially disappeared at about pI 7.5. This NI band was missing or scarce in the parotid saliva and had an amino acid composition rich in glycine, lysine, serine, glutamic acid, aspartic acid, and histidine. This protein was considered to be one of the major HA-reactive proteins in human whole saliva.