Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP 3 -PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP 3 receptor (IP 3 R)-evoked calcium release results in SK channel-dependent hyperpolarization of prefrontal neurons. However, the effects of IP 3 R signaling on prefrontal function have not been investigated. The present findings demonstrate that blockade of IP 3 R or SK channels in the prefrontal cortex enhances WM performance in rats, suggesting that both arms of the PI cascade influence prefrontal cognitive function.The prefrontal cortex coordinates and controls cognitive and emotional processes utilizing appropriate judgment, flexibility, and attention (Goldman-Rakic 1995a,b;Fuster 2000). A hallmark operation of the prefrontal cortex is working memory (WM)-the ability to internally maintain information in the absence of external representation. Debilitating deficits in WM and prefrontal function are associated with numerous conditions including schizophrenia, attention deficit hyperactivity disorder, aging, and stress (Goldman-Rakic 1992;Arnsten 1993;Goldman-Rakic and Selemon 1997;Ramos et al. 2003;Birnbaum et al. 2004). Elucidating mechanisms of cognitive impairment will contribute to identification and development of novel therapeutic targets for treatment of prefrontal decline.Local excitatory circuits are believed to underlie WM operations (Goldman-Rakic 1995a,b) and disruption in prefrontal neuronal activity is associated with WM impairment (GoldmanRakic 1995a,b). Disruptions can arise from altered catecholamine release within the prefrontal cortex. High levels of norepinephrine release, which typically follow a stressor (Rossetti et al. 1990;Finlay et al. 1995), impair WM performance by binding G qcoupled ␣1-adrenoceptors, leading to activation of the phosphatidylinositol (PI) cascade (Garcia-Sainz 1993;Birnbaum et al. 1999Birnbaum et al. , 2004. In the PI pathway, phospholipase C cleaves the phospholipid phosphatidylinositol bisphosphate (PIP 2 ) to generate membrane-bound diacylglycerol (DAG) and diffusible inositol 1, 4, 5-trisphosphate (IP 3 (Kohler et al. 1996). SK channels influence firing frequency by modulating after-hyperpolarization (Pedarzani et al. 2005;Sah 1996) and are therefore positioned to impact the network functions of the prefrontal cortex, which rely on highly synchronized sequences of firing. A recent study by Hagenston et al. (2007) indicates that IP 3 R-SK channel signaling regulates prefrontal neuron firing. IP 3 -mediated release of Ca 2+ resulted in hyperpolarization of layer V pyramidal neurons in rat medial prefrontal slices (Hagenston et al. 2007). This hyperpolarization was reversed by application of the SK channel blocker, apamin (Hagenston et al. 2007), suggesting a mechanistic role of SK channels in prefrontal dysfunction.This study sought to clarify whether IP 3 R sign...

Our results support the concept that providing residents with an individualized learning pathway focusing on clinical outcomes research during residency enables them to successfully publish manuscripts and access mentorship, and may influence subsequent career choice. Implementation of individualized residency program tracks that nurture academic interests along with clinical skills can support career development within medicine residency programs.

PURPOSE: Professional and governmental organizations recommend an ideal US physician workforce composed of at least 40 % primary care physicians. They also support primary care residencies to promote careers in primary care. Our study examines the relationship between graduation from a primary care or categorical internal medicine residency program and subsequent career choice. METHODS: We conducted a cross-sectional electronic survey of a cohort of internal medicine residency alumni who graduated between 2001 and 2010 from a large academic center. Our primary predictor was graduation from a primary care versus a categorical internal medicine program and our primary outcome is current career role. We performed chi-square analysis comparing responses of primary care and categorical residents. RESULTS: We contacted 481 out of 513 alumni, of whom 322 responded (67 %). We compared 106 responses from primary care alumni to 169 responses from categorical alumni. Fifty-four percent of primary care alumni agreed that the majority of their current clinical work is in outpatient primary care vs. 20 % of categorical alumni (p<0.001). While 92.5 % of primary-care alumni were interested in a primary care career prior to residency, only 63 % remained interested after residency. Thirty of the 34 primary care alumni (88 %) who lost interest in a primary care career during residency agreed that their ambulatory experience during residency influenced their subsequent career choice. CONCLUSIONS: A higher percentage of primary care alumni practice outpatient primary care as compared to categorical alumni. Some alumni lost interest in primary care during residency. The outpatient clinic experience may impact interest in primary care.

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