Hippocampal neurons were recorded under conditions in which the recording chamber was varied but its location remained unchanged versus conditions in which an identical chamber was encountered in ...different places. Two forms of neuronal pattern separation occurred. In the variable cue-constant place condition, the firing rates of active cells varied, often over more than an order of magnitude, whereas the location of firing remained constant. In the variable place-constant cue condition, both location and rates changed, so that population vectors for a given location in the chamber were statistically independent. These independent encoding schemes may enable simultaneous representation of spatial and episodic memory information.
Arsenic, a human carcinogen, is genotoxic, although its mechanism(s) of action for tumorigenesis is not well understood. Among the toxicity‐related properties of this chemical are its clastogenic and ...aneugenic activities, as well as its capacity for inducing stress‐response in the form of elevated heat shock protein (HSP) expression. In the present study, we evaluated the effects of Hsp70 expression on arsenite (As)‐induced structural and numerical chromosome anomalies in human cells. Human MCF‐7 Tet‐off cells stably transfected with a pTRE/Hsp70‐1 transgene construct were used to regulate Hsp70 levels prior to in vitro As exposures. Separate cultures of relatively high vs. low Hsp70‐expressing cells were established. A cytokinesis block micronucleus assay with kinetochore immunostaining was used to detect micronuclei (MN) derived from chromosome breakage (K−MN) or loss (K+MN). These studies demonstrated significant increases in micronucleus frequencies in response to As following either a long exposure (5 or 10 μM for 46 hr), or short exposure (10 or 40 μM for 8 hr) protocol. Overall, the long protocol was more efficient in producing K+MN and cells with multiple MN. Overexpressing Hsp70 resulted in significant reductions in the percent of cells positive for MN for both the long and short As exposure protocols. Both K+ and K− types of As‐induced MN were lower in cells with elevated Hsp70 as compared to cells without overexpression of Hsp70. We conclude that the dose and duration of As exposure influence the type as well as amount of chromosomal alteration produced and that inducible Hsp70 protects against both the clastogenic and aneugenic effects of this chemical. Environ. Mol. Mutagen. 40:236–242, 2002. Published 2002 Wiley‐Liss, Inc.
The autonomic nervous system plays a central role in both acute and chronic blood pressure regulation in humans. The activity of the sympathetic branch of the autonomic nervous system is positively ...associated with peripheral resistance, an important determinant of mean arterial pressure in men. In contrast, there is no association between sympathetic nerve activity and peripheral resistance in women before menopause, yet a positive association after menopause. We hypothesized that autonomic support of blood pressure is higher after menopause in women. We examined the effect of ganglionic blockade on arterial blood pressure and how this relates to baseline muscle sympathetic nerve activity in 12 young (25±1 years) and 12 older postmenopausal (61±2 years) women. The women were studied before and during autonomic blockade using trimethaphan camsylate. At baseline, muscle sympathetic nerve activity burst frequency and burst incidence were higher in the older women (33±3 versus 15±1 bursts/min; 57±5 versus 25±2 bursts/100 heartbeats, respectively; P<0.05). Muscle sympathetic nerve activity bursts were abolished by trimethaphan within minutes. Older women had a greater decrease in mean arterial pressure (−29±2 versus −9±2 mm Hg; P<0.01) and total peripheral resistance (−10±1 versus −5±1 mm Hg/L per minute; P<0.01) during trimethaphan. Baseline muscle sympathetic nerve activity was associated with the decrease in mean arterial pressure during trimethaphan (r=−0.74; P<0.05). In summary, our results suggest that autonomic support of blood pressure is greater in older women compared with young women and that elevated sympathetic nerve activity in older women contributes importantly to the increased incidence of hypertension after menopause.
There are sex and sex‐hormone specific differences in autonomic nervous system control of blood pressure. The sympathetic nerve fibers of the autonomic nervous system innervate skeletal muscle blood ...vessels, initiating vasoconstriction, and thus regulate blood flow and vascular tone. This regulation of vascular tone is different between men and women, such that estrogen increases the activity of the b2‐adrenergic receptor activity (causing vasodilation) which offset sympathetically‐mediated vasoconstriction and results in lower blood pressure values in young women. Higher sympathetic nerve activity is associated with greater augmented aortic blood pressure in young men, but lower augmented aortic blood pressure in young women. Such differences in blood pressure regulation will likely have effects that extend beyond blood pressure, affecting blood flow, and ultimately tissue structure and function. For example, higher aortic blood pressure and greater arterial stiffness of the central arteries are associated with white matter hyperintensity fraction in normotensive postmenopausal women and older adults. In addition, there are conditions unique to women, menopause and pregnancy, that further affect blood pressure and blood flow regulation. Pregnancy constitutes a stress that challenges the regulation of blood pressure and blood flow in women. Hypertensive conditions of pregnancy, such as preeclampsia, carry life‐long risk for developing cardiovascular and cerebrovascular diseases. We evaluated the influence of pregnancy history in postmenopausal women on vascular function, cerebral blood flow, and cognition 35 years after pregnancy. Aortic blood pressure was associated with lower cognitive function scores in women with a history of preeclampsia. Additionally, women with a history of preeclampsia had lower cerebral blood flow responses to a vasodilatory stimulus and this was associated with greater intravascular cellular activation. Furthermore, women with a history of preeclampsia and with late‐life hypertension had atrophy in specific regions of the brain, suggesting that pregnancy history may later impact brain structure. Therefore, conditions that a woman may experience during pregnancy may be informative for future risk of disease. In summary, understanding sex‐specific physiological mechanisms, and how this may change over the lifespan is crucial for identification and treatment of individuals at accelerated risk of cardiovascular and cerebrovascular disease.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
Hippocampal neural codes for different, familiar environments are thought to reflect distinct attractor states, possibly implemented in the recurrent CA3 network. A defining property of an attractor ...network is its ability to undergo sharp and coherent transitions between pre-established (learned) representations when the inputs to the network are changed. To determine whether hippocampal neuronal ensembles exhibit such discontinuities, we recorded in CA3 and CA1 when a familiar square recording enclosure was morphed in quantifiable steps into a familiar circular enclosure while leaving other inputs constant. We observed a gradual noncoherent progression from the initial to the final network state. In CA3, the transformation was accompanied by significant hysteresis, resulting in more similar end states than when only square and circle were presented. These observations suggest that hippocampal cell assemblies are capable of incremental plastic deformation, with incongruous information being incorporated into pre-existing representations.
Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies ...often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young (
= 20; 25 ± 3 years) and older (
= 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA) compared with young adults (
< 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young (
< 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men (
< 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.
In the hippocampus, spatial and non-spatial parameters may be represented by a dual coding scheme, in which coordinates in space are expressed by the collective firing locations of place cells and ...the diversity of experience at these locations is encoded by orthogonal variations in firing rates. Although the spatial signal may reflect input from medial entorhinal cortex, the sources of the variations in firing rate have not been identified. We found that rate variations in rat CA3 place cells depended on inputs from the lateral entorhinal cortex (LEC). Hippocampal rate remapping, induced by changing the shape or the color configuration of the environment, was impaired by lesions in those parts of the ipsilateral LEC that provided the densest input to the hippocampal recording position. Rate remapping was not observed in LEC itself. The findings suggest that LEC inputs are important for efficient rate coding in the hippocampus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular ...impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically
and
genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.
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