Culture and Hallucinations: Overview and Future Directions

A number of studies have explored hallucinations as complex experiences involving interactions between psychological, biological, and environmental factors and mechanisms. Nevertheless, relatively little attention has focused on the role of culture in shaping hallucinations. This article reviews the published research, drawing on the expertise of both anthropologists and psychologists. We argue that the extant body of work suggests that culture does indeed have a significant impact on the experience, understanding, and labeling of hallucinations and that there may be important theoretical and clinical consequences of that observation. We find that culture can affect what is identified as a hallucination, that there are different patterns of hallucination among the clinical and nonclinical populations, that hallucinations are often culturally meaningful, that hallucinations occur at different rates in different settings; that culture affects the meaning and characteristics of hallucinations associated with psychosis, and that the cultural variations of psychotic hallucinations may have implications for the clinical outcome of those who struggle with psychosis. We conclude that a clinician should never assume that the mere report of what seems to be a hallucination is necessarily a symptom of pathology and that the patient’s cultural background needs to be taken into account when assessing and treating hallucinations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow

For decades it has been known that external potassium (K(+)) ions are rapid and potent vasodilators that increase cerebral blood flow (CBF). Recent studies have implicated the local release of K(+) from astrocytic endfeet—which encase the entirety of the parenchymal vasculature—in the dynamic regulation of local CBF during neurovascular coupling (NVC). It has been proposed that the activation of strong inward rectifier K(+) (K(IR)) channels in the vascular wall by external K(+) is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular K(IR) channels are the major extracellular K(+) sensors in the control of CBF. We propose that K(+) is an ideal mediator of NVC, and discuss K(IR) channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that K(IR) channels, of the K(IR)2 subtype in particular, are present in both the endothelial and smooth muscle cells of parenchymal arterioles and propose that this dual positioning of K(IR)2 channels increases the robustness of the vasodilation to external K(+), enables the endothelium to be actively engaged in neurovascular coupling, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF

Inhibition of vascular smooth muscle inward-rectifier K⁺ channels restores myogenic tone in mouse urinary bladder arterioles

Prolonged decreases in urinary bladder blood flow are linked to overactive and underactive bladder pathologies. However, the mechanisms regulating bladder vascular reactivity are largely unknown. To investigate these mechanisms, we examined myogenic and vasoactive properties of mouse bladder feed arterioles (BFAs). Unlike similar-sized arterioles from other vascular beds, BFAs failed to constrict in response to increases in intraluminal pressure (5–80 mmHg). Consistent with this lack of myogenic tone, arteriolar smooth muscle cell membrane potential was hyperpolarized (−72.8 ± 1.4 mV) at 20 mmHg and unaffected by increasing pressure to 80 mmHg (−74.3 ± 2.2 mV). In contrast, BFAs constricted to the thromboxane analog U-46619 (100 nM), the adrenergic agonist phenylephrine (10 µM), and KCl (60 mM). Inhibition of nitric oxide synthase or intermediate- and small-conductance Ca2+-activated K+channels did not alter arteriolar diameter, indicating that the dilated state of BFAs is not attributable to overactive endothelium-dependent dilatory influences. Myocytes isolated from BFAs exhibited BaCl2(100 µM)-sensitive K+currents consistent with strong inward-rectifier K+(KIR) channels. Notably, block of these KIRchannels “restored” pressure-induced constriction and membrane depolarization. This suggests that these channels, in part, account for hyperpolarization and associated absence of tone in BFAs. Furthermore, smooth muscle-specific knockout of KIR2.1 caused significant myogenic tone to develop at physiological pressures. This suggests that 1) the regulation of vascular tone in the bladder is independent of pressure, insofar as pressure-induced depolarizing conductances cannot overcome KIR2.1-mediated hyperpolarization; and 2) maintenance of bladder blood flow during bladder filling is likely controlled by neurohumoral influences.</jats:p

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

Brain pericytes reside on the abluminal surface of capillaries, and their processes cover similar to 90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth, 1871; Rouget, 1873) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for G(s)-coupled GPCRs and ATP-sensitive potassium (K-ATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and G(q), G(i/o), and G(12/13) signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease

Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP₂ depletion

Significance Capillaries, the smallest blood vessels, mediate the on-demand delivery of oxygen and nutrients required to support the function of active cells throughout the brain. But how blood flow is directed to cells in active brain regions to satisfy their energy needs is poorly understood. We demonstrate that the plasma membrane phospholipid, PIP 2 , is fundamental to sustaining the activity of inwardly rectifying potassium channels—the molecular feature that allows capillary endothelial cells to sense ongoing neuronal activity and trigger an increase in local blood flow. We further show that chemical factors released in the brain, including those associated with neuronal activity, cause changes in the levels of PIP 2 , thereby altering endothelial potassium channel signaling and controlling cerebral blood flow. </jats:p