Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice.

Social deficit is a major feature of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder, but its neural mechanisms remain unclear. Here, we examined neuronal discharge characteristics in the medial prefrontal cortex (mPFC) of IRSp53/Baiap2-mutant mice, which show social deficits, during social approach. We found a decrease in the proportion of IRSp53-mutant excitatory mPFC neurons encoding social information, but not that encoding non-social information. In addition, the firing activity of IRSp53-mutant neurons was less differential between social and non-social targets. IRSp53-mutant excitatory mPFC neurons displayed an increase in baseline neuronal firing, but decreases in the variability and dynamic range of firing as well as burst firing during social and non-social target approaches compared to wild-type controls. Treatment of memantine, an NMDA receptor antagonist that rescues social deficit in IRSp53-mutant mice, alleviates the reduced burst firing of IRSp53-mutant pyramidal mPFC neurons. These results suggest that suppressed neuronal activity dynamics and burst firing may underlie impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice.

Parallel processing of working memory and temporal information by distinct types of cortical projection neurons.

It is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons-two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively-in the deep layer of the medial prefrontal cortex in mice performing a delayed response task. We found stronger target-dependent firing of IT than PT neurons during the delay period. We also found the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons carry more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.

Dynamically changing neuronal activity supporting working memory for predictable and unpredictable durations.

Diverse neural processes have been proposed as the neural basis of working memory. To investigate whether the medial prefrontal cortex (mPFC) relies on different neural processes to mediate working memory depending on the predictability of delay duration, we examined mPFC neural activity in mice performing a delayed response task with fixed (4 s) or random (between 1-7 s) delay durations. mPFC neural activity was strongly influenced by the predictability of delay duration. Nevertheless, mPFC neurons seldom showed persistent activity spanning the entire delay period and instead showed dynamically-changing delay-period activity under both the fixed-delay and random-delay conditions. mPFC neurons conveyed higher working memory information under the random-delay than fixed-delay conditions, possibly due to a higher demand for stable working memory maintenance. Our results suggest that the rodent mPFC may rely on dynamically-changing neuronal activity to maintain working memory regardless of the predictability of delay duration.

Endometrial stromal sarcoma of the sigmoid colon arising in endometriosis: a case report with a review of literatures.

Most of malignant tumors arising in ovarian and extraovarian endometriosis are carcinomas. Mixed mullerian tumor and endometrial stromal sarcoma arising in intestinal endometriosis are rarely described, but its clinicopathologic features have not been well characterized. Here we report a case of endometrial stromal sarcoma of the sigmoid colon arising in endometriosis with a review of six additional cases of endometrial stromal sarcoma arising in intestinal endometriosis found in English literatures. The patients ranged in age from 36 to 64 yr. Presenting symptoms were pain, bloody diarrhea, and tenesmus. Some patients had a previous history of endometriosis. Most of the tumors arose in the rectosigmoid colon. The histologic features were the same as their uterine counterpart. No death of disease had been reported. This rare tumor should not be confused with gastrointestinal stromal tumor clinically and histologically.