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Wenner M.M.,The John B Pierce Laboratory | Taylor H.S.,Gynecology and Reproductive science | Stachenfeld N.S.,The John B Pierce Laboratory | Stachenfeld N.S.,Yale University
Journal of Physiology | Year: 2011

Women are more susceptible to orthostatic intolerance. Peripheral α-adrenergic responsiveness is important in orthostasis and is lower in women compared to men, and is modulated by female sex hormones. We tested the hypothesis that oestradiol attenuates peripheral cutaneous adrenergic responses in women with low orthostatic tolerance (LT), whereas progesterone enhances adrenergic responses in women with high orthostatic tolerance (HT). After completing a maximal lower body negative pressure test to determine level of orthostatic tolerance (cumulative stress index, CSI), women self administered a gonadotropin releasing hormone (GnRH) antagonist for 16 days to suppress endogenous sex hormone production. Oestradiol (E 2, 0.2 mg day -1, patch; days 4-16), and progesterone (P 4, 200 mg day -1, oral; days 12-16) were administered. Skin blood flow responses to graded intradermal microdialysis infusions of noradrenaline (NA) were measured during GnRH antagonist, E 2, and E 2+P 4, in eight HT (s.e.m.=22 ± 1 years, CSI -871 ± 86 mmHg min) and eight LT (21 ± 1 years, CSI -397 ± 65 mmHg min) women. In separate probes, NA was infused alone, and co-infused with the nitric oxide synthase inhibitor N G-monomethyl-l-arginine (l-NMMA, 10 mm), the non-selective cyclooxygenase inhibitor ketorolac tromethamine (Keto, 10 mm), and combined l-NMMA + Keto (10 mm each). Progesterone administration enhanced adrenergic responses in HT women (logEC 50 GnRH -4.02 ± 0.39, E 2+P 4-5.18 ± 0.31, P < 0.05); this response was reversed with Keto (E 2+P 4 logEC 50 NA+Keto -3.82 ± 0.35, P < 0.05). In contrast, no change in adrenergic responsiveness occurred in LT women during any hormone condition. These data indicate differential regulation of cutaneous adrenergic responses by progesterone via the cyclooxygenase pathway in women with high and low orthostatic tolerance. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.


Horst N.K.,The John B Pierce Laboratory | Horst N.K.,Yale University | Laubach M.,The John B Pierce Laboratory | Laubach M.,Yale University
Journal of Neurophysiology | Year: 2012

Neuronal spike activity was recorded in the medial prefrontal cortex (mPFC) as rats performed an operant spatial delayed alternation task. The sensitivities of neurons to choice, outcome, and temporal information- related aspects of the task were examined. About one-third of neurons were sensitive to the location of delayed responding while animals were at one of two spatially distinct response ports. However, many fewer neurons (<10%) maintained choice information over the delay, each exhibiting persistent differences in firing rates for only a portion of the delay. Another third of cells encoded information about behavioral outcomes, and some of these neurons (>20% of all cells) fired at distinct rates in advance of correct and incorrect responses (i.e., prospective encoding of outcome). Other cells were sensitive to reward-related feedback stimuli (>20%), the outcome of the preceding trial (retrospective encoding, 5-10%), and/or the time since a trial was last performed (10-20%). An anatomical analysis of the recording sites found that cells that were sensitive to choice, temporal, and outcome information were commingled within the middle layers of the mPFC. Together, our results suggest that spatial processing is only part of what drives mPFC neurons to become active during spatial working memory tasks. We propose that the primary role of mPFC in these tasks is to monitor behavioral performance by encoding information about recent trial outcomes to guide expectations and responses on the current trial. By encoding these variables, the mPFC is able to exert control over action and ensure that tasks are performed effectively and efficiently. © 2012 the American Physiological Society.


Green B.G.,The John B Pierce Laboratory | Green B.G.,Yale University | Nachtigal D.,The John B Pierce Laboratory
Physiology and Behavior | Year: 2012

Touch and temperature are recognized as important factors in food perception, but much remains to be learned about how they contribute to the perception of flavor. The present paper describes human psychophysical studies that investigated two recently discovered effects of temperature and mechanical stimulation on taste: (1) enhancement of the savory taste of MSG by active tongue and mouth movements, and (2) modulation of the rate of adaptation to sucrose sweetness by temperature. The first study provides evidence that for MSG but not other taste stimuli, movement of the tongue against the palate enhances taste intensity both by increasing spatial summation between opposing gustatory surfaces and by a hypothesized interaction with touch/kinesthesis. The second study shows that the rate of adaptation to sucrose sweetness (but not quinine bitterness) on the tongue tip is strongly influenced by temperature. It is hypothesized that warming slows adaptation to sucrose by increasing the sensitivity of an early stage of taste transduction. Together these results demonstrate that models of flavor perception must include somatosensory stimuli both as components of flavor perception and as modulators of taste. © 2012 Elsevier Inc.


Horst N.K.,The John B Pierce Laboratory | Horst N.K.,Yale University | Laubach M.,The John B Pierce Laboratory | Laubach M.,Yale University
Frontiers in Neuroscience | Year: 2013

An emerging literature suggests that the medial prefrontal cortex (mPFC) is crucial for the ability to track behavioral outcomes over time and has a critical role in successful foraging. Here, we examine this issue by analyzing changes in neuronal spike activity and local field potentials in the rat mPFC in relation to the consumption of rewarding stimuli. Using multi-electrode recording methods, we simultaneously recorded from ensembles of neurons and field potentials in the mPFC during the performance of an operant-delayed alternation task and a variable-interval licking procedure. In both tasks, we found that consummatory behavior (licking) activates many mPFC neurons and is associated with theta-band phase locking by mPFC field potentials. Many neurons that were modulated by the delivery of reward were also modulated when rats emitted bouts of licks during the period of consumption. The majority of these licking-modulated neurons were found in the rostral part of the prelimbic cortex, a region that is heavily interconnected with the gustatory insular cortex and projects to subcortical feeding-related centers. Based on the tight coupling between spike activity, theta-band phase locking, and licking behavior, we suggest that reward-related activity in the mPFC is driven by consummatory behavior. © 2013 Horst and Laubach.


Green B.G.,The John B Pierce Laboratory | Green B.G.,Yale University
Chemical Senses | Year: 2012

An important function of the chemical senses is to warn against dangerous biological and chemical agents in the environment. The discovery in recent years of "taste" receptor cells outside the oral cavity that appear to have protective functions has raised new questions about the nature and scope of the chemical senses in general and of chemesthesis in particular. The present paper briefly reviews these findings within the context of what is currently known about the body's chemically sensitive protective mechanisms, including nonsensory processes that help to expel or neutralize threatening agents once they have been encountered. It is proposed that this array of defense mechanisms constitutes a "chemofensor complex" in which chemesthesis is the most ubiquitous, functionally diverse, and interactive chemosensory component. © The Author 2011. Published by Oxford University Press. All rights reserved.


Wenner M.M.,The John B Pierce Laboratory | Wenner M.M.,Yale University | Stachenfeld N.S.,The John B Pierce Laboratory | Stachenfeld N.S.,Yale University
Journal of Physiology | Year: 2012

Cardiovascular disease remains the leading cause of death for both men and women. Hypertension is less prevalent in young women compared with young men, but menopausal women are at greater risk for hypertension compared with men of similar age. Despite these risks, women do not consistently receive first line treatment for the early stages of hypertension, and the greater morbidity in menopause reflects this neglect. This review focuses on ovarian hormone effects on the cardiovascular and water regulatory systems that are associated with blood pressure control in women. The study of ovarian hormones within young women is complex because these hormones fluctuate across the menstrual cycle, and these fluctuations can complicate conclusions regarding sex differences. To better isolate the effects of oestrogen and progesterone on the cardiovascular and water regulation systems, we developed a model to transiently suppress reproductive function followed by controlled hormone administration. Sex differences in autonomic regulation of blood pressure appear related to ovarian hormone exposure, and these hormonal differences contribute to sex differences in hypertension and orthostatic tolerance. Oestrogen and progesterone exposure are also associated with plasma volume expansion, and a leftward shift in the osmotic operating point for body fluid regulation. In young, healthy women, the shift in osmoregulation appears to have only a minor effect on overall body water balance. Our overarching conclusion is that ovarian hormone exposure is the important underlying factor contributing to differences in blood pressure and water regulation between women and men, and within women throughout the lifespan. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.


Small D.M.,The John B Pierce Laboratory | Small D.M.,Yale University
Brain Structure and Function | Year: 2010

The sense of taste exists so that organisms can detect potential nutrients and toxins. Despite the fact that this ability is of critical importance to all species there appear to be significant interspecies differences in gustatory organization. For example, monkeys and humans lack a pontine taste relay, which is a critical relay underlying taste and feeding behavior in rodents. In addition, and of particular relevance to this special issue, the primary taste cortex appears to be located further caudally in the insular cortex in humans compared to in monkeys. The primary aim of this paper is to review the evidence that supports this possibility. It is also suggested that one parsimonious explanation for this apparent interspecies differences is that if, as Craig suggests, the far anterior insular cortex is newly evolved and unique to humans, then the human taste cortex may only appear to be located further caudally because it is no longer the anterior-most section of insular cortex. In addition to discussing the location of taste representation in human insular cortex, evidence is presented to support the possibility that this region is better conceptualized as an integrated oral sensory region that plays role in feeding behavior, rather than as unimodal sensory cortex. © 2010 Springer-Verlag.


Small D.M.,The John B Pierce Laboratory
Brain structure & function | Year: 2010

The sense of taste exists so that organisms can detect potential nutrients and toxins. Despite the fact that this ability is of critical importance to all species there appear to be significant interspecies differences in gustatory organization. For example, monkeys and humans lack a pontine taste relay, which is a critical relay underlying taste and feeding behavior in rodents. In addition, and of particular relevance to this special issue, the primary taste cortex appears to be located further caudally in the insular cortex in humans compared to in monkeys. The primary aim of this paper is to review the evidence that supports this possibility. It is also suggested that one parsimonious explanation for this apparent interspecies differences is that if, as Craig suggests, the far anterior insular cortex is newly evolved and unique to humans, then the human taste cortex may only appear to be located further caudally because it is no longer the anterior-most section of insular cortex. In addition to discussing the location of taste representation in human insular cortex, evidence is presented to support the possibility that this region is better conceptualized as an integrated oral sensory region that plays role in feeding behavior, rather than as unimodal sensory cortex.


Small D.M.,The John B Pierce Laboratory | Small D.M.,Yale University
Physiology and Behavior | Year: 2012

Flavor is perhaps the most multi-modal of all of our sensory experiences. Here flavor is defined as a perception that includes gustatory, oral-somatosensory, and retronasal olfactory signals that arise from the mouth as foods and beverages are consumed. Although the sights, sounds and smells of foods that occur just before, or in the absence of eating, can impact flavor perception, it is argued that these sensory signals exert their influence by creating expectations based upon prior associations. The primary aim of the paper is to review anatomical and neurophysiological data towards an understanding of how the core sensory signals combine in the central nervous system of humans. Based upon the extant literature it is proposed that taste, oral-somatosensory and olfactory inputs are first integrated in the anterior ventral insula. The core flavor percept is then conveyed to upstream regions in the brainstem and thalamus, as well as downstream regions in the amygdala, orbitofrontal cortex and anterior cingulate cortex to produce the rich flavorful experiences that guide our feeding behavior. © 2012 Elsevier Inc.


Veldhuizen M.G.,The John B Pierce Laboratory | Veldhuizen M.G.,Yale University | Small D.M.,The John B Pierce Laboratory | Small D.M.,Yale University
Chemical Senses | Year: 2011

The insular cortex is implicated in general attention and in taste perception. The effect of selective attention to taste on insular responses may therefore reflect a general effect of attention or it may be (taste) modality specific. To distinguish between these 2 possibilities, we used functional magnetic resonance imaging to evaluate brain response to tastes and odors while subjects passively sampled the stimuli or performed a detection task. We found that trying to detect a taste (attention to taste) resulted in activation of the primary taste cortex (anterior and mid-dorsal insula) but not in the primary olfactory cortex (piriform). In contrast, trying to detect an odor (attention to odor) increased activity in primary olfactory but not primary gustatory cortex. However, we did identify a region of far anterior insular cortex that responded to both taste and odor "searches." These results demonstrate modality-specific activation of primary taste cortex by attention to taste and primary olfactory cortex by attention to odor and rule out the possibility that either response reflects a general effect of attentional deployment. The findings also support the existence of a multimodal region in far anterior insular cortex that is sensitive to directed attention to taste and smell. © The Author 2011. Published by Oxford University Press. All rights reserved.

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