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PubMed2001

Gene expression profiling in the amygdala: an approach to examine the molecular substrates of mammalian behavior.

The molecular substrates of behavior have been difficult to assess because of the large number of messenger RNAs (mRNAs) expressed in a given brain region, the heterogeneous composition of the CNS, and the complexity of mammalian behavior. To gain insight into the molecular components of behavior requires an understanding of the anatomy associated with a specific behavior and the ability to examine multiple gene expression in discrete brain regions. Neuroanatomical and behavioral studies have demonstrated that the amygdaloid complex is an essential component of the neural pathways mediating behaviors, such as fear, anxiety, learning, and memory. The amygdala is composed of several interconnected subnuclei and it is the modulation of information, as it flows through these subnuclei, that underlies amygdala function. To examine the molecular components of the amygdala, we have combined the antisense RNA (aRNA) amplification procedure with microarray technology. This experimental approach permits the simultaneous detection and quantification of numerous mRNAs in fixed tissue sections. Our initial experiment examines region-specific gene expression in naïve mice in order to map the molecular relationship between the subregions of the amygdala. This report provides a general overview of the techniques used to examine regional gene expression, suggests future experiments, and describes a theoretical framework for examining the molecular analysis of behavior.

Amygdala↗

PubMed1992

Treatment of lower urinary tract dysfunction in patients with multiple sclerosis. Committee of the European Study Group of SUDIMS (Sexual and Urological Disorders in Multiple Sclerosis)

Bladder symptoms in patients with multiple sclerosis (MS) are common and usually arise as a result of spinal lesions which interrupt the neural pathways connecting the pontine micturition centre to the sacral spinal cord. Thus these symptoms are particularly likely to occur in those with lower limb neurological deficits. Fortunately bladder dysfunction in MS is rarely associated with serious upper tract disease so that the problem is usually one of symptomatic management. Lower urinary tract symptoms may be both "irritative" or "obstructive" in nature and can be explained in terms of underlying detrusor hyperreflexia and incomplete bladder emptying. Treatment is aimed at minimising both these effects. Oral anticholinergic medication can be effective in reducing detrusor hyperreflexia and intermittent catheterisation is used to reduce abnormally high post micturition residual volumes. With this simple treatment, often used in combination, many less severely affected patients with MS can gain considerable improvement in controlling urinary continence.

Administration, Oral↗

PubMed2004

Organization of suprachiasmatic nucleus projections in Syrian hamsters (Mesocricetus auratus): an anterograde and retrograde analysis.

Circadian rhythms in physiology and behavior are controlled by pacemaker cells located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The mammalian SCN can be classified into two subdivisions (core and shell) based on the organization of neuroactive substances, inputs, and outputs. Recent studies in our laboratory indicate that these subdivisions are associated with functional specialization in Syrian hamsters. The core region, marked by calbindin-D(28K) (CalB)-containing cells, expresses light-induced, but not rhythmic, clock genes. In the shell compartment, marked by vasopressinergic cells and fibers, clock gene expression is rhythmic. Given these findings, an important question is how photic and rhythmic information are integrated and communicated from each of these regions to effector areas. The present study used localized, intra-SCN iontophoretic injections of the anterograde tracer biotinylated dextran amine (BDA) to investigate intra-SCN connectivity and the neural pathways by which information is communicated from SCN subregions to targets. Intra-SCN connections project from the core to the shell compartment of the SCN, but not from the shell to the CalB region of the SCN. Retrograde tracing experiments were performed using cholera toxin-beta (CTB) to determine more specifically whether SCN efferents originated in the core or shell using neurochemical markers for the rhythmic (vasopressin) and light-induced (CalB) SCN subregions. The combined results from anterograde and retrograde experiments suggest that all SCN targets receive information from both the light-induced and rhythmic regions of the SCN (albeit to varying degrees) and indicate that light and rhythmic information may be integrated both within the SCN and at target effector areas.

Animals↗

PubMed1991

Spectral sensitivity of ON and OFF responses from the optic nerve of goldfish.

The vertebrate retina processes visual information in parallel neural pathways known as the ON and OFF pathways. These pathways encode increments and decrements of light independently as excitatory responses. We examined the photopic spectral response of ON and OFF mechanisms in goldfish by measuring the sensitivity of optic nerve responses to the onset and termination of stimuli of various wavelengths. Using various adapting backgrounds, we found that the ON and OFF responses have different spectral sensitivities. The weighting of the cone inputs to the responses was estimated by an algebraic summation model. This model suggests that for the ON response, input from S-cones is stronger and more independent than for the OFF response, and M- and L-cones show stronger antagonism in the ON response than in the OFF response. The OFF response probably receives input from all cone types, but spectral antagonism is weak and its dominant input is from L-cones.

Animals↗

PubMed2002

Visualizing the neural bases of a disconnection syndrome with diffusion tensor imaging.

Disconnection syndromes are often conceptualized exclusively within cognitive box-and-arrow diagrams unrelated to brain anatomy. In a patient with alexia in his left visual field resulting from a posterior callosal lesion, we illustrate how diffusion tensor imaging can reveal the anatomical bases of a disconnection syndrome by tracking the degeneration of neural pathways and relating it to impaired fMRI activations and behavior. Compared to controls, an abnormal pattern of brain activity was observed in the patient during word reading, with a lack of activation of the left visual word form area (VWFA) by left hemifield words. Statistical analyses of diffusion images revealed a damaged fiber tract linking the left ventral occipito-temporal region to its right homolog across the lesioned area of corpus callosum and stopping close to the areas found active in fMRI. The behavioral disconnection syndrome could, thus, be related functionally to abnormal fMRI activations and anatomically to the absence of a connection between those activations. The present approach, based on the "negative tracking" of degenerated bundles, provides new perspectives on the understanding of human brain connections and disconnections.

Adult↗

PubMed1994

The auditory-vocal-respiratory axis in birds.

A series of studies is described which in general aim to identify two sets of neural linkages in the brain and spinal cord of songbirds and non-songbirds, these avian types differing along a dimension of 'complexity of vocal communication'. One set of linkages is postulated to link the vocal system with the respiratory system, since birds, like humans, require controlled expiration in order to vocalize normally. The other set is thought to link the auditory system with the vocal system, at least in songbirds, because they are dependent upon auditory feedback for vocal learning. The systems and their linkages can be regarded as forming an 'auditory-vocal-respiratory axis', around which the animal's communication system evolves and revolves. The experimental strategy used was one which began at the periphery (the abdominal expiratory muscles), then progressively identified more central neural structures using retrograde transport methods in partial combination with recordings of single cell activity. The projections delineated by these methods were then defined in detail by anterograde tracing methods. The results of the studies confirmed the expectation that the vocal and respiratory systems have many neural elements in common. They also suggested that songbirds and non-songbirds possess similar neural pathways in the brainstem and spinal cord for the control of both vocalization and respiration but indicated that there may be significant differences between the two types of birds in the degree to which the telencephalon is able to modulate respiratory-vocal activity downstream. Thus, whereas there is a cascade of descending projections terminating upon syringeal and laryngeal motoneurons and expiratory premotor neurons in both songbirds and non-songbirds, the most rostral origin of this cascade is the telencephalic nucleus robustus archistriatalis in (male) songbirds but, apparently, the dorsomedial nucleus of the intercollicular complex of the midbrain (DM) in pigeons. Connectional studies of the auditory system in pigeons delineated a series of projections which originate in Field L2, the primary telencephalic auditory area, and leave the telencephalon via the nucleus archistriatum intermedium, pars medialis (Aivm), after traversing a minimum of three synapses within the telencephalon.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1981

Cephalic phase, reflex insulin secretion. Neuroanatomical and physiological characterization.

Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that the CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.

Animals↗

PubMed2004

Spatial conditional associative learning: effects of thalamo-hippocampal disconnection in rats.

Unilateral lesions to the anterior thalamic nuclei (ATN) and the hippocampus (H) were made in opposite hemispheres in the rat to examine whether these brain structures form part of a functional neural pathway underlying spatial learning and memory. In the first experiment, rats were tested on a spatial-visual conditional associative task in which they had to learn to approach one of two stimuli depending on the spatial context in which the stimuli were embedded. The rats were subsequently trained on delayed forced alternation, a spatial working memory task known to be sensitive to the effects of ATNxH damage. Rats with ATNxH lesions were impaired in the acquisition of both tasks in comparison with normal control animals. The findings support the idea that the anterior thalamic nuclei and the hippocampus are critical components of an anatomical system subserving spatial memory and suggest that these brain regions work in a dependent fashion during the performance of certain spatial learning tasks.

Analysis of Variance↗

PubMed2003

Nissen fundoplication has a vagolytic effect on the lower esophageal sphincter.

BACKGROUND: Laparoscopic Nissen fundoplication is an increasingly utilized option for the treatment of gastroesophageal reflux disease (GERD). However, many questions remain as to the mechanism by which this operation prevents GERD in those without hiatal hernias or incompetent lower esophageal sphincters (LES). It is known that these patients experience reflux due to excess transient lower esophageal sphincter relaxations (TLESR), inappropriate and short-lived relaxation of the LES and crural diaphragm. The purpose of this study was to determine if Nissen fundoplication affects the neural pathways involved in the TLESR reflex. METHODS: Five dogs were anesthetized and intubated. Both vagal nerves and the right phrenic nerve were isolated. A continuous water perfusion manometric catheter was situated at the LES. The nerves were then electrically stimulated and the resultant pressure at the LES measured at baseline, and during and after an open Nissen fundoplication. RESULTS: The mean LES pressures before dissection, after esophago-gastric mobilization, and after fundoplication were 47 +/- 13 mmHg, 21 +/- 9 mmHg, and 14 +/- 4 mmHg, respectively. All differences were significant. There was no change noted in LES pressure with stimulation of either or both of the phrenic nerves without concomitant vagal stimulation. CONCLUSION: Nissen fundoplication may prevent GERD in those without a hiatal hernia or incompetent LES by disrupting the efferent vagal fibers to the LES. Such fibers mediate TLESR which are responsible for GERD in these patients.

Animals↗

PubMed2000

DL-phenylalanine markedly potentiates opiate analgesia - an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system.

In the author's clinical experience, concurrent treatment with DL-phenylalanine (DLPA) often appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain. An analysis of this phenomenon suggests that it may be mediated, at least in part, by up-regulation of the 'endogenous analgesia system' (EAS), a neural pathway that projects caudally from medullary nuclei to the dorsal horn of the spinal column; when stimulated by chronic pain or therapeutic measures such as opiates or acupuncture, the EAS suppresses activation of second-order pain-receptive neurons in the dorsal horn, and thereby alleviates pain. Since serotonin and enkephalins are key neurotransmitters in the EAS, it is reasonable to predict that measures which promote serotonin activity (such as 5-hydroxytryptophan and serotonin-reuptake inhibitors) as well as enkephalin activity (such as D-phenylalanine, an enkephalinase inhibitor) should potentiate EAS-mediated analgesia - a view consistent with much previous medical research. Comprehensive support of the EAS with well-tolerated nutrients and pharmaceuticals may amplify the analgesic efficacy of chronic opiate therapy, while enabling dosage reductions that minimize opiate side-effects. Analogously, this approach may complement the efficacy of acupuncture and other analgesic measures that activate the EAS.

Analgesia↗

PubMed2002

Attenuated drinking response induced by angiotensinergic activation of subfornical organ projections to the paraventricular nucleus in estrogen-treated rats.

The present study was carried out to examine whether estrogen modulates the drinking response caused by activation of neural pathways from the subfornical organ (SFO) to the hypothalamic paraventricular nucleus (PVN) in the female rat. Microinjection of angiotensin II (ANG II) into the SFO elicited drinking in ovariectomized female rats that were treated with either propylene glycol (PG) vehicle or estradiol benzoate (EB). The amount of water intake induced by the ANG II injection was significantly greater in the PG-treated than in the EB-treated animals. In both groups, previous injections of either saralasin, an ANG II antagonist, or phentolamine, an alpha-adrenoceptor antagonist, bilaterally into the PVN resulted in the significant attenuation of the drinking response to ANG II, whereas similar injections of saline vehicle into the PVN were without effect. These results suggest that the circulating estrogen may act to reduce the drinking response that is mediated through angiotensinergic and alpha-adrenergic mechanisms in the PVN in response to angiotensinergic activation of SFO efferent projections.

Angiotensins↗

PubMed2002

Event-related skin conductance responses to musical emotions in humans.

While the reasons underlying musical emotions are unclear, music is nevertheless a powerful elicitor of emotion, and as such, may induce autonomic nervous system responses. One typical measure of this neural pathway is the skin conductance response (SCR). This response generally depends upon stimulus arousal, one of the two motivational determinants of emotion. The objective of the present study was to verify whether emotional reactions to music elicit such event-related autonomic responses. To this aim, four musical emotions varying in arousal were employed: fear, happiness, sadness and peacefulness. SCRs were found to be greater with the two more stimulating emotions, fear and happiness, as compared to the two more relaxing emotions, sadness and peacefulness (P<0.05). In addition, subjects' ratings of the emotional clarity for each excerpt did not parallel the corresponding SCRs magnitudes. The results show that SCRs can be evoked and modulated by musical emotional arousal, but are not sensitive to emotional clarity. While several studies have been performed with visual scenes and environmental sounds, the present study brings similar evidence from the musical domain.

Acoustic Stimulation↗

PubMed2003

Functional activation using apparent diffusion coefficient-dependent contrast allows better spatial localization to the neuronal activity: evidence using diffusion tensor imaging and fiber tracking.

Recent studies suggested that functional activation using apparent diffusion coefficient (ADC) contrast can be used to detect synchronized functional MRI (fMRI) signal changes during brain activation. Such changes may reflect better spatial localization to the smaller vessels, which are closely coupled to the true neuronal activation. Since it is generally believed that there are neural pathways among neuronally relevant areas, methods that would allow clear delineation of such pathways could help validate the neuronal relevance of the activated functional areas. The development of diffusion tensor imaging (DTI) has shown promise in detailed nerve fiber tracking. In this report, DTI was adopted to track the fiber connections among the discrete areas determined using the ADC contrast, in an effort to confirm the neuronal origin of these activated areas. As a comparison, activated areas using blood oxygenation level-dependent (BOLD) contrast were also obtained. Our results showed that the areas determined by the ADC contrast consistently allowed better fiber tracking within, while the BOLD-activated areas were more spatially diffused due to the smearing effect of brain vasculature, rendering the task of fiber tracking more difficult. This observation provides converging evidence that the activated areas using ADC contrast are more closely coupled to the neuronal activity than those using BOLD contrast.

Brain↗

PubMed1990

Perineural tumor extension through the foramen ovale: evaluation with MR imaging.

Perineural tumor extension is a form of metastatic disease in which primary tumors spread along neural pathways and gain access to non-contiguous regions. The treatment and prognosis are altered when perineural extension occurs. Awareness and proper evaluation are critical for the radiologist. The third (mandibular) division of the trigeminal nerve (V3), passing through the skull base via the foramen ovale, is a common route of perineural spread of head and neck lesions. Seven patients with perineural tumor involvement of the mandibular nerve were evaluated with magnetic resonance imaging with use of standard spin-echo pulse sequences emphasizing T1-weighted information. Three patients had adenoid cystic carcinoma, three had squamous cell carcinoma, and one had well-differentiated lymphocytic lymphoma of the orbit. MR imaging signs of perineural involvement included smooth thickening of V3, concentric expansion of the foramen ovale, replacement of the normal trigeminal cistern hypointensity by an isointense mass, lateral bulging of cavernous sinus dural membranes, and atrophy of masticator muscles.

Carcinoma, Adenoid Cystic↗

PubMed1989

Neuropsychological "systems efficiency" and positron emission tomography.

Positron emission tomography (PET) has dramatically improved our ability to examine the functioning of the living brain. PET studies of neural pathways of the major sensory modalities--auditory, visual, somatosensory--have confirmed many traditional neuropsychological concepts, such as cross-lateral representation and regional functioning to particular primary sensory cortical areas. Other PET studies have used radioisotopes to examine relationships between radiopharmaceutical agents and neurobehavioral functioning in both normal and neuropathological states. In some areas, PET methodology requires further refinement. For example, effort should be made to develop the technology to do multiple scans within a short time frame; statistical procedures to examine relationships between neuropsychological tasks and the activity or presence of radiopharmaceutical agents in multiple sites; adequate controls for experimental error; and activation paradigms controlling the nonspecific effects of simple arousal. PET activation models of cognition suggest that a "systems efficiency" approach to assessing neuropsychological test performance involving both serial and parallel processing would be useful. These developments will improve empirical methodology and our understanding of brain-behavior relationships.

Arousal↗

PubMed1997

New aspects of gastric adaptive relaxation, reflex after food intake for more food: involvement of capsaicin-sensitive sensory nerves and nitric oxide.

To accommodate the intake of food or liquid, gastric reservoir functions are important as the physiological reflex. There exist two major responses as a reservoir function of the stomach; adaptive and receptive relaxations. Adaptive relaxation is a reflex in which the fundus of the stomach dilates in response to small increases in intragastric pressure when food enters the stomach. Receptive relaxation is a reflex in which the gastric fundus dilates when food passes down the pharynx and the esophagus. The mechanisms of these two types of functional responses are to some extent different, although a nitric oxide (NO) dependent non adrenergic, non cholinergic neural pathway is involved in the both relaxation reflexes. Adaptive relaxation is an intragastric pressure induced reflex. Stretch of the gastric wall activates the mechanoreceptors in gastric mucosa (Mu), which generate impulses carried by the capsaicin-sensitive afferent sensory neuron. The sensory neuron can synapse on the inhibitory efferent neuron directly or activate it via interneurons of the myenteric plexus. This leads to the release of NO from the nitroxergic efferent neuron, which causes relaxation of circular muscle and hence of the fundus. Alternatively, an axon reflex causes the NO release from the sensory neuron, resulting in hexamethonium resistant gastric relaxation. Receptive relaxation is mediated by vagal motor fibers. In contrast with the pressure-induced adaptive relaxation, ganglionic nicotinic transmission is essential in the vagally induced relaxation. VIP and CGRP are important neurotransmitters of the inhibitory sensory neuron, which, however, may not mediate both adaptive and receptive relaxations. Disorders of these reservoir functions result in symptoms of early satiety and anorexia, which are the major symptoms of patients with functional dyspepsia.

Adaptation, Physiological↗

PubMed2000

Neurophysiologic evaluation of auditory recognition memory in healthy newborn infants and infants of diabetic mothers.

OBJECTIVES: We evaluated the integrity of neural pathways for auditory recognition memory in normal newborn infants (n = 32) and infants of diabetic mothers (IDMs, n = 25). IDMs are at risk for fetal metabolic abnormalities that potentially damage recognition memory pathways. We hypothesized that newborn IDMs would have recognition memory deficits that would be correlated with later cognitive development. STUDY DESIGN: Recognition memory was assessed with event-related potentials (ERPs). Neonatal ERPs elicited by the maternal voice were compared with those elicited by a stranger's voice. The Bayley Scales of Infant Development were administered at 1 year of age. RESULTS: Infants in both the control and IDM groups demonstrated recognition of the maternal voice, but their ERP patterns differed. Both groups demonstrated increased amplitude and latency for the "P2" peak elicited by the maternal voice compared with the stranger's voice. In the control group the stranger's voice also elicited a negative slow wave, which was attenuated in the IDMs. The negative slow wave correlated significantly with the 1-year Mental Developmental Index. CONCLUSIONS: The presence of a specific neonatal ERP pattern indicated better 1-year cognitive development in infants in the control and IDM groups. ERPs from IDMs demonstrated subtle evidence of recognition memory impairments.

Analysis of Variance↗

PubMed1998

Penile erection produced by microstimulation of the sacral spinal cord of the cat.

The sacral neural pathways mediating penile erection in the cat were studied by measuring the change in cavernous sinus pressure (CSP) elicited by stimulation of the sacral ventral roots or by microstimulation of the sacral spinal cord. Ventral root stimulation revealed that the S1 segment rather than S2 and S3 spinal segments could evoke the largest CSP responses. Microstimulation in the S1 spinal cord elicited large CSP responses but small or no bladder contractions. Maximal CSP responses were evoked by microstimulation in the middle of the S1 ventral horn, 1.6-2.8 mm below the cord surface and midway between the midline and the lateral edge of the gray matter. The area was 200-400 microm wide (medial to lateral) and extended 1-2 mm in the rostrocaudal direction. Maximal CSP responses to spinal cord microstimulation were elicited by stimulus intensities of 50-150 microA, at a pulse width of 0.2 ms and at frequencies of 3040 Hz and occurred after delay of 8-40 s. This study suggests that focal microstimulation of the sacral spinal cord might be useful in eliciting penile erectile activity in patients with spinal cord injury.

Animals↗