Browsing by keyword "Prefrontal cortex"
Now showing items 1-4 of 4
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Altered neural connectivity in adult female rats exposed to early life social stressThe use of a variety of neuroanatomical techniques has led to a greater understanding of the adverse effects of stress on psychiatric health. One recent advance that has been particularly valuable is the development of resting state functional connectivity (RSFC) in clinical studies. The current study investigates changes in RSFC in F1 adult female rats exposed to the early life chronic social stress (ECSS) of the daily introduction of a novel male intruder to the cage of their F0 mothers while the F1 pups are in the cage. This ECSS for the F1 animals consists of depressed maternal care from their F0 mothers and exposure to conflict between their F0 mothers and intruder males. Analyses of the functional connectivity data in ECSS exposed adult females versus control females reveal broad changes in the limbic and reward systems, the salience and introspective socioaffective networks, and several additional stress and social behavior associated nuclei. Substantial changes in connectivity were found in the prefrontal cortex, nucleus accumbens, hippocampus, and somatosensory cortex. The current rodent RSFC data support the hypothesis that the exposure to early life social stress has long term effects on neural connectivity in numerous social behavior, stress, and depression relevant brain nuclei. Future conscious rodent RSFC studies can build on the wealth of data generated from previous neuroanatomical studies of early life stress and enhance translational connectivity between animal and human fMRI studies in the development of novel preventative measures and treatments.
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cPLA2alpha-/- sympathetic neurons exhibit increased membrane excitability and loss of N-Type Ca2+ current inhibition by M1 muscarinic receptor signalingGroup IVa cytosolic phospholipase A2 (cPLA2alpha) mediates GPCR-stimulated arachidonic acid (AA) release from phosphatidylinositol 4,5-bisphosphate (PIP2) located in plasma membranes. We previously found in superior cervical ganglion (SCG) neurons that PLA2 activity is required for voltage-independent N-type Ca2+ (N-) current inhibition by M1 muscarinic receptors (M1Rs). These findings are at odds with an alternative model, previously observed for M-current inhibition, where PIP2 dissociation from channels and subsequent metabolism by phospholipase C suffices for current inhibition. To resolve cPLA2alpha's importance, we have investigated its role in mediating voltage-independent N-current inhibition (~40%) that follows application of the muscarinic agonist oxotremorine-M (Oxo-M). Preincubation with different cPLA2alpha antagonists or dialyzing cPLA2alpha antibodies into cells minimized N-current inhibition by Oxo-M, whereas antibodies to Ca2+-independent PLA2 had no effect. Taking a genetic approach, we found that SCG neurons from cPLA2alpha-/- mice exhibited little N-current inhibition by Oxo-M, confirming a role for cPLA2alpha. In contrast, cPLA2alpha antibodies or the absence of cPLA2alpha had no effect on voltage-dependent N-current inhibition by M2/M4Rs or on M-current inhibition by M1Rs. These findings document divergent M1R signaling mediating M-current and voltage-independent N-current inhibition. Moreover, these differences suggest that cPLA2alpha acts locally to metabolize PIP2 intimately associated with N- but not M-channels. To determine cPLA2alpha's functional importance more globally, we examined action potential firing of cPLA2alpha+/+ and cPLA2alpha-/- SCG neurons, and found decreased latency to first firing and interspike interval resulting in a doubling of firing frequency in cPLA2alpha-/- neurons. These unanticipated findings identify cPLA2alpha as a tonic regulator of neuronal membrane excitability.
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Differential Contributions of Lateral Prefrontal Cortex Regions to Visual Memory ProcessesThe prefrontal cortex (PFC) is the seat of higher level control operations, with recognition and working memory processes critical to those operations. While not strictly organized by the principle of localization, certain functions are clearly more associated with one region than another within PFC dynamic systems. We set out to test the hypothesis that active visual memory comparison (making judgments of novelty) was most associated with the ventrolateral prefrontal cortex (VLPFC), while the monitoring and manipulation of visual information was most associated with the mid-dorsolateral prefrontal cortex (mid-DLPFC). The current study used magnetic resonance volumetry to define the VLPFC and mid-DLPFC as regions of interest (ROIs), and analyzed those in relation to types of visual memory processes. We observed a functional dissociation of working memory within the PFC corresponding to comparison versus monitoring processes. One of the blocks of the monitoring and manipulation task showed a significant positive relationship with left, right, and total mid-DLPFC volume, with no significant relationship to the VLPFC. Performance on a memory comparison task bore a significant positive relationship with right and total VLPFC volume, and no relationship with the mid-DLPFC.
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Resting-state functional connectivity, cortical GABA, and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic resonance imaging and spectroscopy studyPostpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy ((1)H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p = 0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p = 0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r = +0.661, p = 0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r = +0.522, p = 0.000; left amygdala: r = +0.651, p = 0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p = 0.03) and positively correlated with intra DMPFC connectivity (r = +0.548, p = 0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.
