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PubMed1993

Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link?

Although the mechanisms regulating the cerebral microcirculation during neural activity have been the subject of inquiry for a century or more, the mediators responsible for the changes in cerebral blood flow still remain to be clearly identified. The discovery that nitric oxide, a powerful cerebrovasodilator, is produced by active neurons has led to the hypothesis that this agent could be the long-sought mediator 'coupling' brain activity to cerebral blood flow. This hypothesis is supported by recent experimental data suggesting that nitric oxide participates in the maintenance of resting cerebral blood flow and in the cerebrovasodilatation elicited by increased neural activity. In this article, this evidence is critically reviewed and discussed in the context of general principles of cerebrovascular regulation.

Animals↗
PubMed2005

Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping.

In mammals, retinal ganglion cell (RGC) projections initially intermingle and then segregate into a stereotyped pattern of eye-specific layers in the dorsal lateral geniculate nucleus (dLGN). Here we found that in mice deficient for ephrin-A2, ephrin-A3 and ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted. In contrast, mice that lacked correlated retinal activity did not segregate eye-specific inputs. Inhibition of correlated neural activity in ephrin mutants led to overlapping retinal projections that were located in inappropriate regions of the dLGN. Thus, ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers.

Animals↗
PubMed1996

Persisting versus sustained neural activity: effects on transient N100m response.

Previous evidence from animal and human studies suggests that neural activity, both during a continuous tone and persisting after the offset of a first tone, can prolong the latency and enhance the amplitude of a transient response to a second tone. Our results showed that the latency of N100m to a second tone presented to the opposite ear was prolonged equally in both conditions. Unexpectedly, the effects on response strength strongly depended on stimulus laterality: the ipsilateral but not the contralateral N100m to the second tone was enhanced by the simultaneous presence of the first when compared with the effect of the preceding tone. This suggests that sustained neural activity during a continuous tone can release inhibition normally induced by ipsilateral stimulation.

Acoustic Stimulation↗
PubMed1976

The effects of neurally active amino acids on prolactin secretion.

Several neurally active amino acids were injected into the third ventricle of anesthetized male rats. Two or eight mumole of GABA produced significant increases in the plasma concentrations of prolactin (PRL), indicating increased PRL release from the pituitary. Two mumole of glycine was also effective in elevating PRL levels. The intraventricular injection of the lowest dose of GABA (1.0 mumole), glutamate (0.4 or 2.3 mumole), lysine (0.2 or 2.0 mumole), or 0.9% NaCl did not alter PRL levels significantly. Plasma PRL concentrations did not increase following the injection of GABA or glycine directly into the anterior pituitary gland. The results suggest that GABA and glycine may play a role in the neural regulation of PRL secretion.

Amino Acids↗
PubMed2001

Parasympathetic inhibition of sympathetic neural activity to the pancreas.

The present study tested the hypothesis that activation of the parasympathetic nervous system could attenuate sympathetic activation to the pancreas. To test this hypothesis, we measured pancreatic norepinephrine (NE) spillover (PNESO) in anesthetized dogs during bilateral thoracic sympathetic nerve stimulation (SNS; 8 Hz, 1 ms, 10 mA, 10 min) with and without (randomized design) simultaneous bilateral cervical vagal nerve stimulation (VNS; 8 Hz, 1 ms, 10 mA, 10 min). During SNS alone, PNESO increased from the baseline of 431 +/- 88 pg/min to an average of 5,137 +/- 1,075 pg/min (P < 0.05) over the stimulation period. Simultaneous SNS and VNS resulted in a significantly (P < 0.01) decreased PNESO response [from 411 +/- 61 to an average of 2,760 +/- 1,005 pg/min (P < 0.05) over the stimulation period], compared with SNS alone. Arterial NE levels increased during SNS alone from 130 +/- 11 to approximately 600 pg/ml (P < 0.05); simultaneous SNS and VNS produced a significantly (P < 0.05) smaller response (142 +/- 17 to 330 pg/ml). Muscarinic blockade could not prevent the effect of VNS from reducing the increase in PNESO or arterial NE in response to SNS. It is concluded that parasympathetic neural activity opposes sympathetic neural activity not only at the level of the islet but also at the level of the nerves. This neural inhibition is not mediated via muscarinic mechanisms.

Animals↗
PubMed1989

Influence of muscle mass on sympathetic neural activation during isometric exercise.

The primary purpose of this study was to determine whether the sympathetic neural activation induced by isometric exercise is influenced by the size of the contracting muscle mass. To address this, in nine healthy subjects (aged 19-27 yr) we measured heart rate, systolic arterial blood pressure, and muscle sympathetic nerve activity in the leg (MSNA; peroneal nerve) before (control) and during 2.5 min of isometric handgrip exercise (30% of maximal voluntary force). Exercise was performed with the right and left arms separately and with both arms simultaneously (random order). During exercise, heart rate, systolic pressure, and MSNA increased above control under all conditions (P less than 0.05). For each variable, the magnitudes of the increases from control to the end of exercise were significantly greater when exercise was performed with two arms compared with either arm alone (P less than 0.05). In general, the increases in heart rate, systolic pressure, and MSNA elicited during two-arm exercise were significantly less than the simple sums of the responses evoked during exercise of each arm separately. These findings indicate that the magnitude of the sympathetic neural activation evoked during isometric exercise in humans is determined in part by the size of the active muscle mass. In addition, our results suggest that the sympathetic cardiovascular adjustments elicited during exercise of separate limbs are not simply additive but instead exhibit an inhibitory interaction (i.e., neural occlusion).

Adult↗
PubMedDate not supplied

Changes in muscle size, architecture, and neural activation after 20 days of bed rest with and without resistance exercise.

Nine healthy men carried out head-down bed rest (BR) for 20 days. five subjects (TR) performed isometric, bilateral leg extension exercise every day, while the other four (NT) did not. Before and after BR, maximal isometric knee extension force was measured. Neural activation was assessed using a supramaximal twitch interpolated over voluntary contraction. From a series cross-sectional magnetic resonance imaging scans of the thigh, physiological cross-sectional areas (PCSA) of the quadriceps muscles were estimated (uncorrected PCSA, volume/estimated fibre length). Decrease in mean muscle force after BR was greater in NT [-10.9 (SD 6.9)%, P < 0.05] than in TR [0.5 (SD 7.9)%, not significant]. Neural activation did not differ between the two groups before BR, but after BR NT showed smaller activation levels. Pennation angles of the vastus lateralis muscle, determined by ultrasonography, showed no significant changes in either group. The PCSA decreased in NT by -7.8 (SD 0.8)% (P < 0.05) while in TR PCSA showed only an insignificant tendency to decrease [-3.8 (SD 3.8)%]. Changes in force were related more to changes in neural activation levels than to those in PCSA. The results suggest that reduction of muscle strength by BR is affected by a decreased ability to activate motor units, and that the exercise used in the present experiment is effective as a countermeasure.

Adolescent↗
PubMed2002

Event-related neural activity associated with habit and recollection.

The neural activity associated with conscious recollection and habit was examined using event-related brain potentials. In a training phase, participants learned A-B, A-C word associations in which the probability of specific responses was varied. Once a habit was established, participants studied and were tested on a series of short lists consisting of word pairs seen in training. The process-dissociation procedure was used to estimate the contribution of habit and recollection to memory performance. Habit estimates reflected the probability with which information was presented in training but recollection estimates did not show this effect. Recollection was associated with sustained negativity over the parieto-occipital region, which was opposite in polarity over the frontal regions. Indices of habit strength were associated with a sustained positivity over left fronto-temporal regions and a sustained negativity over right fronto-central regions. Partial-least squares analyses revealed two significant latent variables that distinguished recollection and habit, consistent with the distinction between consciously controlled and automatic influences of memory.

Adult↗
PubMed2000

Quantification of optical signals with electrophysiological signals in neural activities of Di-4-ANEPPS stained rat hippocampal slices.

We have quantified the optical signals of synaptically induced neural activities in an in vitro brain slice preparation in terms of electrophysiological signals. The qualification was done using electrophysiologically well known neural activities in the CA1 area of rat hippocampal slices stained with externally applied fluorescent voltage-sensitive dye (VSD; Di-4-ANEPPS). Together with a newly designed CCD-based digital high-speed camera system and epi-fluorescent optics, our improvements were made on a protocol for staining using a newly designed chamber system. These improvements enabled us to make stable and reliable recordings of optical signals and electrophysiological measurements without affecting the physiological status and to make a quantitative comparison between them. The time course and amplitude of the optical signal showed fair agreement with intracellular and extracellular recordings, and was stable over 2 h. The optical signal followed synaptically induced long-term potentiation (LTP) as monitored by the electrophysiological signals. A regional difference in the amount of LTP was found in optical signals and was confirmed in the electrophysiological signals. These results demonstrate the capabilities of our improved method as an alternative but more potent tool to measure the neuronal activities of brain slice in addition to electrophysiological method.

Action Potentials↗
PubMed1998

Derivatization of progesterone to a neurally active steroid by pituitary neurointermediate lobe.

The melanotrophs of the neurointermediate lobe and peptidergic terminals of the neural lobe are regulated by gamma-aminobutyric acid (GABA) via GABA-A receptors and therefore, may be important sites for the modulatory actions of neurally active steroids. These steroid compounds might be produced peripherally, synthesized de novo in the pituitary, or derivatized from circulating steroids, each pathway having different physiological implications. In the present study, we show that neurointermediate lobe tissue can derivatize progesterone to the neurally active steroid 3 alpha-hydroxy-5 alpha-pregnan-20-one. The neurointermediate lobe was found to be four times as active as anterior pituitary and mediobasal hypothalamus in conversion of progesterone to 3 alpha-hydroxy-5 alpha-pregnan-20-one; mediobasal hypothalamus was relatively more active in the production of the intermediate 5 alpha-pregnan-3,20-dione. The identity of the compounds was confirmed by the method of serial isotopic dilution. We observed rates of synthesis in the neurointermediate lobe consistent with the production of physiologically relevant quantities of 3 alpha-hydroxy-5 alpha-pregnan-20-one from concentrations of progesterone which can occur naturally. In support of these findings, we demonstrate the presence of 3 alpha-hydroxysteroid oxidoreductase in neurointermediate lobe by immunocytochemistry.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

Regional changes in human cerebral blood flow during dipyridamole stress: neural activation in the thalamus and prefrontal cortex.

Intravenous dipyridamole increases the concentration of circulating adenosine and produces coronary vasodilation. However, it decreases global cerebral blood flow (CBF) due to hyperventilation side effect of adenosine. In the present study, changes in regional CBF during dipyridamole stress were identified in detail. In 11 healthy men (51-71 years of age), CBF was measured by positron emission tomography with oxygen-15-labeled water at rest (baseline) and during dipyridamole stress. All images were normalized to global CBF and transformed to standard brain anatomy. A t map between baseline and dipyridamole stress conditions was then created on a pixel-by-pixel basis. CBF was globally decreased during dipyridamole stress. However, a significant relative increase in CBF was observed bilaterally in the thalamus and prefrontal cortex, indicating neural activation in these regions. Adenosine plays an important role in the production of anginal pain by stimulation of A(1) adenosine receptors. Neural activation in the thalamus and prefrontal cortex during angina pectoris has been reported. Although no subject felt chest pain during dipyridamole stress, neural activation in the thalamus and prefrontal cortex indicates that stimulation of A(1) adenosine receptors during dipyridamole stress may produce input from the heart to the thalamus through the vagal fiber.

Blood Pressure↗
PubMed1994

Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii).

Is patterned neural activity in immature, prefunctioning sensory systems a general phenomenon? Such patterning has been found in the prenatal visual and somatosensory systems. We have now identified patterning in the immature auditory system of a prehearing mammal, the tammar wallaby. Neurones recorded in vivo from the eighth nerve and cochlear nucleus at pouch days 94-122 discharged in bursts with rhythmic inter-spike intervals. Our findings are applied to the argument that neural activity is vital to sensory development.

Acoustic Stimulation↗
PubMed1989

The organization of spatial coding in the hippocampus: a study of neural ensemble activity.

Neural activity was recorded from local groups of hippocampal single units in rats performing a spatial-memory task. The organization of functional correlates in these neural ensembles was investigated by examining the spatial relationships among the place fields of single units in each ensemble. The distance and overlap between place fields were determined together with the tuning of cellular activity to behavioral variables, including direction, speed, and turning angle during movements within place fields. The place fields of recorded neural ensembles were significantly clustered: closer in space and considerably more overlapped than chance when compared statistically with Monte Carlo simulations. Just as single units often have significant firing in more than one distinct location in the environment (subfields), the ensembles had multiple and distinct clusters of overlapping subfields. In addition, proximity and overlap between place fields were significantly, but weakly, correlated with similarity in optimal movement tuning parameters. These results suggest that the hippocampus maintains a local organization with respect to place fields despite having no apparent large-scale isomorphism with the spatial environment. The organization of multiple, clustered place fields with correlated movement tuning properties in small neural ensembles suggests the existence of functional neural ensembles serving to encode multiple sensory and behavioral aspects of a place or event. Such an organization is similar to that observed for neocortical association areas afferent to the hippocampal system.

Animals↗
PubMed2004

Monitoring neural activity and [Ca2+] with genetically encoded Ca2+ indicators.

Genetically encoded Ca2+ indicators (GECIs) based on fluorescent proteins (XFPs) and Ca2+-binding proteins [like calmodulin (CaM)] have great potential for the study of subcellular Ca2+ signaling and for monitoring activity in populations of neurons. However, interpreting GECI fluorescence in terms of neural activity and cytoplasmic-free Ca2+ concentration ([Ca2+]) is complicated by the nonlinear interactions between Ca2+ binding and GECI fluorescence. We have characterized GECIs in pyramidal neurons in cultured hippocampal brain slices, focusing on indicators based on circularly permuted XFPs [GCaMP (Nakai et al., 2001), Camgaroo2 (Griesbeck et al., 2001), and Inverse Pericam (Nagai et al., 2001)]. Measurements of fluorescence changes evoked by trains of action potentials revealed that GECIs have little sensitivity at low action potential frequencies compared with synthetic [Ca2+] indicators with similar affinities for Ca2+. The sensitivity of GECIs improved for high-frequency trains of action potentials, indicating that GECIs are supralinear indicators of neural activity. Simultaneous measurement of GECI fluorescence and [Ca2+] revealed supralinear relationships. We compared GECI fluorescence saturation with CaM Ca2+-dependent structural transitions. Our data suggest that GCaMP and Camgaroo2 report CaM structural transitions in the presence and absence of CaM-binding peptide, respectively.

Action Potentials↗
PubMed2006

Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia.

Recent theoretical and empirical research on schizophrenia converges on the notion that core aspects of the pathophysiology of the disorder may arise from a dysfunction in the coordination of distributed neural activity. Synchronization of neural responses in the beta-band (15-30 Hz) and gamma-band range (30-80 Hz) has been implicated as a possible neural substrate for dysfunctional coordination in schizophrenia. To test this hypothesis, we examined the electroencephalography (EEG) activity in 19 patients with a Diagnostic and Statistical Manual of Mental Disorder, edition IV criteria, diagnosis of schizophrenia and 19 healthy control subjects during a Gestalt perception task. EEG data were analyzed for phase synchrony and induced spectral power as an index of neural synchronization. Schizophrenia patients were impaired significantly in the detection of images that required the grouping of stimulus elements into coherent object representations. This deficit was accompanied by longer reaction times in schizophrenia patients. Deficits in Gestalt perception in schizophrenia patients were associated with reduced phase synchrony in the beta-band (20-30 Hz), whereas induced spectral power in the gamma-band (40-70 Hz) was mainly intact. Our findings suggest that schizophrenia patients are impaired in the long-range synchronization of neural responses, which may reflect a core deficit in the coordination of neural activity and underlie the specific cognitive dysfunctions associated with the disorder.

Action Potentials↗
PubMed1989

Gustatory-salivary reflex: neural activity of sympathetic and parasympathetic fibers innervating the submandibular gland of the hamster.

Electrophysiological experiments were performed to clarify the neural control mechanisms subserving gustatory-salivary reflex in anesthetized and decerebrate hamsters. Efferent neural activities of postganglionic sympathetic and preganglionic parasympathetic fibers, innervating the submandibular gland, were recorded when taste stimuli were infused into the oral cavity. Neural activities of primary gustatory afferents were also recorded from the chorda tympani (innervating the anterior part of the tongue) and the glossopharyngeal nerve (innervating the posterior part of the tongue). The parasympathetic fibers showed a low rate of spontaneous discharges (about 0.3 Hz), and responded tonically in an excitatory manner to taste stimulation. The magnitude of parasympathetic activity was highly correlated with the magnitude of gustatory afferent responses of the chorda tympani rather than that of the glossopharyngeal nerve. On the other hand, the sympathetic fibers showed irregular burst discharges (1.5 burst/s), and the rate of burst discharges was increased in response to high concentrations of HCl (0.03 M) or NaCl (1 M) solutions. Deafferentation experiments suggest that the parasympathetic activity is mainly influenced by gustatory information via the chorda tympani, while the sympathetic activity can be evoked by both the chorda tympani and glossopharyngeal nerve.

Action Potentials↗
PubMed2006

Temporal characteristics of neural activity related to target detection during visual search.

A previous MEG study on neural activities during the orientation singleton search showed that both efficient and inefficient searches shared a common neural network and the search efficiency was determined by a neural process executed in the temporal and parietal areas. The target segmentation stage, however, remains to be elucidated. In the present study, MEG and fMRI experiments were conducted, and moment-magnitudes of equivalent current dipoles were estimated with an fMRI-constrained MEG multi-dipole method to obtain differences between target-present and -absent conditions in each brain region for the whole time course. The dipole moments around the calcarine sulcus (CaS) and posterior fusiform gyrus (pFuG) increased at latencies around 70-350 ms. Activity around the CaS consisted of a prominent and a subsequent smaller but still obvious peak (117, 215 ms); the first peak showed no difference between conditions, while the second peak was significantly larger in the target-present condition. Activity around the pFuG had a prominent peak (125 ms) and subsequent small activity (237 ms), whereas the target's presence or not had no influence on either activity. The activity of the right intraparietal sulcus (IPS) was significantly larger than that for the left IPS at latencies around 196 ms irrespective of the target's presence or not. The activity of the other brain regions such as the posterior superior temporal sulcus, cingulate sulcus and central sulcus showed no difference between target conditions. The results demonstrate that neural activities of multiple regions had different temporal characteristics, and the later activity around the CaS was related to the target segregation from its surroundings during the orientation contrast search.

Adult↗