When conditions change, organisms need to learn about the changed conditions without interfering with what they already know. To do so, they can assign the new learning to a new "state" and the old learning to a previous state. This state assignment is fundamental to behavioral flexibility. Cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) are necessary for associative information to be compartmentalized in this way, but the mechanism by which they do so is unknown. Here we addressed this question by recording putative CINs from the DMS in rats performing a task consisting of a series of trial blocks, or states, that required the recall and application of contradictory associative information. We found that individual CINs in the DMS represented the current state throughout each trial. These state correlates were not observed in dorsolateral striatal CINs recorded in the same rats. Notably, DMS CIN ensembles tracked rats' beliefs about the current state such that, when states were miscoded, rats tended to make suboptimal choices reflecting the miscoding. State information held by the DMS CINs also depended completely on the orbitofrontal cortex, an area that has been proposed to signal environmental states. These results suggest that CINs set the stage for recalling associative information relevant to the current environment by maintaining a real-time representation of the current state. Such a role has novel implications for understanding the neural basis of a variety of psychiatric diseases, such as addiction or anxiety disorders, in which patients generalize inappropriately (or fail to generalize) between different environments.
The known sensitivity of joint scintigraphy in following the course of fracture healing caused the authors to believe that this radiologic technique might be valuable in the management of osteochondritis dissecans (OCD). Accordingly, 99mTc-diphosphonate joint scintigraphy was used on 18 patients with OCD of the knee. The average age was 13 1/2 years. The scintigrams were repeated at 6-week intervals until healing had occurred. When the diagnosis of OCD was established by standard roentgenograms and joint scintigraphy, the patients were placed on an activity restriction program, attempting to reach a symptom-free level. The patients were followed for an average of 18 months. Ninety-five scans were categorized according to their level of scintigraphic activity. This led to a discrete four-part scintigraphic classification that is indicative of the extent of healing or progression of this condition, and precedes changes seen on standard x-rays by months. Joint scintigraphy also rules out anomalies of ossification in the diagnosis of OCD since an anomaly should have a normal scintigraphic appearance. We have concluded that joint scintigraphy is valuable in the management of OCD because of its superior sensitivity to changes in the activity of the lesion. As experience is gained with this technique, those cases that should be prophylactically surgically stabilized may be indicated.
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