scholarly journals Convergence of biological and psychological perspectives on cognitive coordination in schizophrenia

2003 ◽  
Vol 26 (1) ◽  
pp. 65-82 ◽  
Author(s):  
William A. Phillips ◽  
Steven M. Silverstein
Keyword(s):  
Brain Function ◽  
Important Class ◽  
Neural Basis ◽  
Ion Flow ◽  
Control Gain ◽  
Mode Of Operation ◽  
Voltage Dependent ◽  
Nmda Channels ◽  
Flow Through ◽  
Cortical Regions

AbstractThe concept of locally specialized functions dominates research on higher brain function and its disorders. Locally specialized functions must be complemented by processes that coordinate those functions, however, and impairment of coordinating processes may be central to some psychotic conditions. Evidence for processes that coordinate activity is provided by neurobiological and psychological studies of contextual disambiguation and dynamic grouping. Mechanisms by which this important class of cognitive functions could be achieved include those long-range connections within and between cortical regions that activate synaptic channels via NMDA-receptors, and which control gain through their voltage-dependent mode of operation. An impairment of these mechanisms is central to PCP-psychosis, and the cognitive capabilities that they could provide are impaired in some forms of schizophrenia. We conclude that impaired cognitive coordination due to reduced ion flow through NMDA-channels is involved in schizophrenia, and we suggest that it may also be involved in other disorders. This perspective suggests several ways in which further research could enhance our understanding of cognitive coordination, its neural basis, and its relevance to psychopathology.

scholarly journals Generalized Anxiety Disorder in Adults: Focus on Pregabalin

2011 ◽  
Vol 3 ◽  
pp. CMPsy.S5069 ◽  
Author(s):  
Mark J. Boschen
Keyword(s):  
Anxiety Disorder ◽  
Generalized Anxiety Disorder ◽  
Preliminary Evidence ◽  
Future Research ◽  
Generalized Anxiety ◽  
Inhibitory Neurotransmitter ◽  
Ion Flow ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Flow Through

Generalized anxiety disorder (GAD) is a chronic illness which impacts significantly on an individual's functioning and quality of life. Pregabalin is a novel structural analogue of the inhibitory neurotransmitter GABA, acting to reduce calcium ion flow through the α2δ subunit of pre-synaptic voltage-dependent calcium channels. Pregabalin has been used in treatment of GAD in a total of eight published controlled trials. In each trial, pregabalin has demonstrated a superiority over placebo, with response rates of over 40% in all studies, including patients on lower doses. One study has provided preliminary evidence for the efficacy of pregabalin in treatment of GAD in older adults. Pregabalin is generally well tolerated, with the most common adverse events being dizziness and somnolence. Adverse effects are generally mild-to-moderate, and transient. Pregabalin has low abuse potential. Limitations of the current literature are discussed, and directions for future research are proposed.

scholarly journals Status of the Intracellular Gate in the Activated-not-open State of Shaker K+ Channels

2005 ◽  
Vol 126 (5) ◽  
pp. 419-428 ◽  
Author(s):  
Donato del Camino ◽  
Max Kanevsky ◽  
Gary Yellen
Keyword(s):  
Conformational Changes ◽  
Charge Movement ◽  
Ion Flow ◽  
K Channels ◽  
Closed State ◽  
Channel Opening ◽  
Activated State ◽  
Form Part ◽  
Voltage Dependent ◽  
Flow Through

Voltage-dependent K+ channels like Shaker use an intracellular gate to control ion flow through the pore. When the membrane voltage becomes more positive, these channels traverse a series of closed conformations before the final opening transition. Does the intracellular gate undergo conformational changes before channel opening? To answer this question we introduced cysteines into the intracellular end of the pore and studied their chemical modification in conditions favoring each of three distinct states, the open state, the resting closed state, and the activated-not-open state (the closed state adjacent to the open state). We used two independent ways to isolate the channels in the activated-not-open state. First, we used mutations in S4 (ILT; Smith-Maxwell, C.J., J.L. Ledwell, and R.W. Aldrich. 1998. J. Gen. Physiol. 111:421–439; Ledwell, J.L., and R.W. Aldrich. 1999. J. Gen. Physiol. 113:389–414) that separate the final opening step from earlier charge-movement steps. Second, we used the open channel blocker 4-aminopyridine (4-AP), which has been proposed to promote closure of the intracellular gate and thus specifically to stabilize the activated-not-open state of the channels. Supporting this proposed mechanism, we found that 4-AP enters channels only after opening, remaining trapped in closed channels, and that in the open state it competes with tetraethylammonium for binding. Using these tools, we found that in the activated-not-open state, a cysteine located at a position considered to form part of the gate (Shaker 478) showed higher reactivity than in either the open or the resting closed states. Additionally, we have found that in this activated state the intracellular gate continued to prevent access to the pore by molecules as small as Cd2+ ions. Our results suggest that the intracellular opening to the pore undergoes some rearrangements in the transition from the resting closed state to the activated-not-open state, but throughout this process the intracellular gate remains an effective barrier to the movement of potassium ions through the pore.

scholarly journals Tom40, the Pore-Forming Component of the Protein-Conducting Tom Channel in the Outer Membrane of Mitochondria

2001 ◽  
Vol 153 (6) ◽  
pp. 1151-1160 ◽  
Author(s):  
Uwe Ahting ◽  
Michel Thieffry ◽  
Harald Engelhardt ◽  
Reiner Hegerl ◽  
Walter Neupert ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Lipid Membranes ◽  
Dependent Manner ◽  
Core Element ◽  
Ion Flow ◽  
Tom Complex ◽  
Voltage Dependent ◽  
Flow Through ◽  
Α Helix ◽  
Main Component

Tom40 is the main component of the preprotein translocase of the outer membrane of mitochondria (TOM complex). We have isolated Tom40 of Neurospora crassa by removing the receptor Tom22 and the small Tom components Tom6 and Tom7 from the purified TOM core complex. Tom40 is organized in a high molecular mass complex of ∼350 kD. It forms a high conductance channel. Mitochondrial presequence peptides interact specifically with Tom40 reconstituted into planar lipid membranes and decrease the ion flow through the pores in a voltage-dependent manner. The secondary structure of Tom40 comprises ∼31% β-sheet, 22% α-helix, and 47% remaining structure as determined by circular dichroism measurements and Fourier transform infrared spectroscopy. Electron microscopy of purified Tom40 revealed particles primarily with one center of stain accumulation. They presumably represent an open pore with a diameter of ∼2.5 nm, similar to the pores found in the TOM complex. Thus, Tom40 is the core element of the TOM translocase; it forms the protein-conducting channel in an oligomeric assembly.

Modeling of the Ionized Fluid Flow through a Cone-Shaped Nanopore

2007 ◽  
Vol 121-123 ◽  
pp. 1089-1092 ◽  
Author(s):  
Jian Zhong Fu ◽  
Xiao Bing Mi ◽  
Yong He ◽  
Zi Chen Chen
Keyword(s):  
Fluid Flow ◽  
Theoretical Analysis ◽  
Cross Section ◽  
Debye Length ◽  
Velocity Profiles ◽  
Gradual Change ◽  
Ion Flow ◽  
Flow Through

Theoretical analysis of the ionized fluid flowing through a cone-shaped nanopore is presented. The internal cross section of the cone-shaped channel is in the range from micro- to nanometer and gradual change from larger to smaller than the Debye length for the ions. The model is developed to predict the ionized fluid flow behaviors in cone-shaped micro/nanochannels. The velocity profiles of ion flow that occur in nanopores are obtained.

scholarly journals Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

2020 ◽  
Vol 21 (19) ◽  
pp. 7212
Author(s):  
Mayumi Nishi
Keyword(s):  
Child Abuse ◽  
Hpa Axis ◽  
Brain Function ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Emotional Behavior ◽  
Neural Basis ◽  
The Brain

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

Perceptual Representations and the Vividness of Stimulus-Triggered and Stimulus-Independent Experiences

2020 ◽  
Vol 15 (5) ◽  
pp. 1200-1213 ◽  
Author(s):  
Peter Fazekas ◽  
Georgina Nemeth ◽  
Morten Overgaard
Keyword(s):  
Working Memory ◽  
Mental Imagery ◽  
Information Exchange ◽  
Activity Patterns ◽  
Mind Wandering ◽  
Brain Regions ◽  
Neural Basis ◽  
Fine Grained ◽  
Common Framework ◽  
Cortical Regions

In recent years, researchers from independent subfields have begun to engage with the idea that the same cortical regions that contribute to on-line perception are recruited during and underlie off-line activities such as information maintenance in working memory, mental imagery, hallucinations, dreaming, and mind wandering. Accumulating evidence suggests that in all of these cases the activity of posterior brain regions provides the contents of experiences. This article is intended to move one step further by exploring specific links between the vividness of experiences, which is a characteristic feature of consciousness regardless of its actual content, and certain properties of the content-specific neural-activity patterns. Investigating the mechanisms that underlie mental imagery and its relation to working memory and the processes responsible for mind wandering and its similarities to dreaming form two clusters of research that are in the forefront of the recent scientific study of mental phenomena, yet communication between these two clusters has been surprisingly sparse. Here our aim is to foster such information exchange by articulating a hypothesis about the fine-grained phenomenological structure determining subjective vividness and its possible neural basis that allows us to shed new light on these mental phenomena by bringing them under a common framework.

Continuum Model for Ion Gating in Cochlear Hair Cells

1997 ◽  
Vol 50 (11S) ◽  
pp. S210-S215
Author(s):  
Charles R. Steele
Keyword(s):  
Flow Rate ◽  
Continuum Model ◽  
Mechanical Response ◽  
Elastic Interaction ◽  
Physical Parameters ◽  
Cochlear Hair Cells ◽  
Ion Flow ◽  
Basic Fluid ◽  
Spring Force ◽  
Flow Through

The details of ion flow in cells are important for the macro mechanical response of sensory organs, as in the inner ear of vertebrates. A continuum model for the flow of an ionized fluid through a pore in an elastic wall is considered. With this, the electro-mechanical behavior is readily computed. An interesting result is that two equilibria exist for the flow through a pore with a soft elastic entrance region. At one equilibrium point, the entrance opening is more restricted and the corresponding ion flow rate is much lower. Thus it appears that the tendency of ion channels to pop from an open to a closed state may be a consequence of basic fluid-elastic interaction. With the simple continuum model, various effects can be explored. One is the presence of an external spring force, corresponding to the force of the tip fiber between stereocilia. Another is the effect of an adjacent membrane and pore. The input physical parameters are reasonable and the results for flow rate are consistent with experimental measurements.

A Descriptive Framework for the Evaluation of Stress Effects on Operator Performance

2001 ◽  
Vol 45 (13) ◽  
pp. 948-956 ◽  
Author(s):  
P.A. Hancock ◽  
H.C.N. Ganey ◽  
M. Mouloua ◽  
E. Salas ◽  
R. Gilson ◽  
...  
Keyword(s):  
Brain Function ◽  
The Body ◽  
Interactive Effects ◽  
Cognitive Responses ◽  
Stress Effects ◽  
Operator Performance ◽  
Mode Of Operation ◽  
And Performance ◽  
Psychological Challenge ◽  
Descriptive Framework

In this paper we provide a general descriptive framework that relates the action of stress on operator performance capacity. The key advantage of our approach is that it allows us to capture simultaneously the influences of both physical and cognitive forms of stress and their singular and interactive effects on response efficiency. This is accomplished within the model since we propose that response processes to physiological challenge and psychological challenge are fundamentally identical in their mode of operation. By considering the commonalities of brain function with the response processes of other organs of the body, we can now use the extensive existing body of physiological insight to provide us with guiding principles to explore undoubtedly more complex cognitive responses to stress. This descriptive framework represents the foundation upon which a fully articulated theory of stress and performance is being erected.

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