34 research outputs found

    Birth Regulates the Initiation of Sensory Map Formation through Serotonin Signaling

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    SummaryAlthough the mechanisms underlying the spatial pattern formation of sensory maps have been extensively investigated, those triggering sensory map formation during development are largely unknown. Here we show that the birth of pups instructively and selectively regulates the initiation of barrel formation in the somatosensory cortex by reducing serotonin concentration. We found that preterm birth accelerated barrel formation, whereas it did not affect either barreloid formation or barrel structural plasticity. We also found that serotonin was selectively reduced soon after birth and that the reduction of serotonin was triggered by birth. The reduction of serotonin was necessary and sufficient for the effect of birth on barrel formation. Interestingly, the regulatory mechanisms described here were also found to regulate eye-specific segregation in the visual system, suggesting that they are utilized in various brain regions. Our results shed light on roles of birth and serotonin in sensory map formation

    A Corticostriatal Path Targeting Striosomes Controls Decision-Making under Conflict

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    A striking neurochemical form of compartmentalization has been found in the striatum of humans and other species, dividing it into striosomes and matrix. The function of this organization has been unclear, but the anatomical connections of striosomes indicate their relation to emotion-related brain regions, including the medial prefrontal cortex. We capitalized on this fact by combining pathway-specific optogenetics and electrophysiology in behaving rats to search for selective functions of striosomes. We demonstrate that a medial prefronto-striosomal circuit is selectively active in and causally necessary for cost-benefit decision-making under approach-avoidance conflict conditions known to evoke anxiety in humans. We show that this circuit has unique dynamic properties likely reflecting striatal interneuron function. These findings demonstrate that cognitive and emotion-related functions are, like sensory-motor processing, subject to encoding within compartmentally organized representations in the forebrain and suggest that striosome-targeting corticostriatal circuits can underlie neural processing of decisions fundamental for survival.National Institutes of Health (U.S.) (R01 MH060379)National Institute of Mental Health (U.S.) (R01 MH060379)United States. Defense Advanced Research Projects Agency (W911NF-10-1-0059)United States. Army Research Office (W911NF-10-1-0059

    Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making

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    Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, “rational” decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict.National Institute of Mental Health (Grant R01 MH060379)CHDI Foundation (Award A-5552)Army Research Office (Contract W911NF-10-1-0059

    Partial Biopterin Deficiency Disturbs Postnatal Development of the Dopaminergic System in the Brain*

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    Postnatal development of dopaminergic system is closely related to the development of psychomotor function. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of dopamine and requires tetrahydrobiopterin (BH4) as a cofactor. To clarify the effect of partial BH4 deficiency on postnatal development of the dopaminergic system, we examined two lines of mutant mice lacking a BH4-biosynthesizing enzyme, including sepiapterin reductase knock-out (Spr−/−) mice and genetically rescued 6-pyruvoyltetrahydropterin synthase knock-out (DPS-Pts−/−) mice. We found that biopterin contents in the brains of these knock-out mice were moderately decreased from postnatal day 0 (P0) and remained constant up to P21. In contrast, the effects of BH4 deficiency on dopamine and TH protein levels were more manifested during the postnatal development. Both of dopamine and TH protein levels were greatly increased from P0 to P21 in wild-type mice but not in those mutant mice. Serotonin levels in those mutant mice were also severely suppressed after P7. Moreover, striatal TH immunoreactivity in Spr−/− mice showed a drop in the late developmental stage, when those mice exhibited hind-limb clasping behavior, a type of motor dysfunction. Our results demonstrate a critical role of biopterin in the augmentation of TH protein in the postnatal period. The developmental manifestation of psychomotor symptoms in BH4 deficiency might be attributable at least partially to high dependence of dopaminergic development on BH4 availability
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