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P Müller-Preuss

Publications and source records attributed to P Müller-Preuss.

16 recordsLinked to original sources

Cytokine secretion in squirrel monkeys.

The squirrel monkey, a non-human New World primate, has several endocrine peculiarities, including a 10-fold higher plasma cortisol concentration than Old World primates, such as man. Glucocorticoids are known to have immunomodulatory properties. We therefore measured cytokine levels in supernatants of in vitro cultures of mononuclear cells from the peripheral blood of squirrel monkeys and humans. We stimulated monocytes and lymphocytes with lipopolysaccharide (LPS) and phytohemagglutinin (PHA) in the presence or absence of hydrocortisone. Squirrel monkey monocytes secreted a more than 100-fold lower level of interleukin-1 beta (IL-1 beta) but a four-fold higher level of transforming growth factor beta (TGF-beta) than human monocytes, whereas the secretion of other cytokines, such as tumor necrosis factor alpha (TNF-alpha), TNF-beta and interleukin 2 (IL-2), did not differ between squirrel monkeys and humans. However, in squirrel monkey lymphocytes, the PHA-stimulated secretion of TNF-alpha was much greater than that of TNF-beta. Our results support the view that in squirrel monkeys there are subtle adaptations in some immune functions, particularly linked to the hypothalamic-pituitary-adrenal (HPA) system rather than a global suppression of the immune system.

Adult↗

Auditory responsive cortex in the squirrel monkey: neural responses to amplitude-modulated sounds.

The neural response to amplitude-modulated sinus sounds (AM sound) was investigated in the auditory cortex and insula of the awake squirrel monkey. It was found that 78.1% of all acoustically driven neurons encoded the envelope of the AM sound; the remaining 21.9% displayed simple On, On/Off or Off responses at the beginning or the end of the stimulus sound. Those neurons with AM coding were able to encode the AM sound frequency in two different ways: (1) the spikes followed the amplitude modulation envelopes in a phase locked manner; (2) the spike rate changed significantly with changing modulation frequencies. As reported in other species, the modulation transfer functions for rate showed higher modulation frequencies than the phase-locked response. Both AM codings exhibited a filter characteristic for AM sound. Whereas 46.6% of all neurons had the same filter characteristic for both the spike discharge and the phase-locked response, the remaining neurons displayed combinations of different filter types. The discharge pattern of a neuron to simple tone or noise bursts suggests the behaviour of this neuron when AM sound is used as the stimulus. Neurons with strong onset responses to tone/noise bursts tended to have higher phase-locked AM responses than neurons with weak onset responses. The spike rate maxima for AM sound showed no relation to the tone/noise burst discharge patterns. Varying modulation depth was encoded by the neuron's ability to follow the envelope cycles and not by the non-phase-locked spike rate frequency. The organization of the squirrel monkey's auditory cortex has previously been established by an anatomical study. We have added two new fields using physiological parameters. All fields investigated showed a clear functional separation for time-critical information processing. The best temporal resolution was shown by the primary auditory field (AI), the first-temporal field (T1) and the parainsular auditory field (Pi). The neural data in these fields and the amplitude modulation frequency range of squirrel monkey calls suggest a similar correlation between vocalization and perception as in human psychophysical data for speech and hearing sensation. The anterior fields in particular failed to follow the AM envelopes. For the first time in a primate, the insula was tested with different sound parameters ranging from simple tone bursts to AM sound. It is suggested that this cortical region plays a role in time-critical aspects of acoustic information processing. The observed best frequencies covered the same spectrum as AI. As in the auditory fields, most neurons in the insula encoded AM sound with different filter types. The high proportion of neurons unable to encode AM sound (40.6%) and the low mean best modulation frequency (9.9 Hz) do not support a prominent role of the insula in temporal information processing.

Acoustic Stimulation↗

Lipopolysaccharide increases EEG delta activity within non-REM sleep and disrupts sleep continuity in rats.

Activation of the immune system by microorganisms or specific microbial constituents promotes non-rapid-eye-movement (REM) sleep (non-REMS). In this study, we assessed the effects of lipopolysaccharide (LPS) on sleep duration, electroencephalogram (EEG) power spectra, and brain temperature (Tbr) in rats. Twenty-four hour recordings were made before and after intraperitoneal injection of vehicle or 30 or 100 micrograms/kg LPS at lights on. During the first 12 h after administration of both doses of LPS, Tbr was elevated, REMS duration was reduced, and non-REMS duration was unchanged, whereas the non-REMS episodes were shortened. EEG activity within non-REMS from 0.5 to 7 Hz was enhanced during hours 3-12. During the second 12-h period, the number of non-REMS and REMS episodes and the total time in both states were increased. EEG activity within non-REMS was mainly reduced in the entire frequency range (0.5-25.5 Hz). The effects of LPS did not differ between the doses. The effects of LPS on EEG power spectra are similar to those observed after sleep deprivation, i.e., a physiological intensification of non-REMS, indicating that both manipulations may activate common sleep EEG regulatory mechanisms. However, the disruption of non-REMS continuity following LPS administration at light onset contrasts the changes induced by sleep deprivation and may reflect an effect of a systemic inflammatory response on sleep maintenance.

Animals↗

Effect of bacterial endotoxin and interleukin-1 beta on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study.

In this study the effect of immune system stimulation and intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1 beta) on hippocampal serotonergic neurotransmission, behavioral activity, and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An in vivo microdialysis method was used to measure hippocampal extracellular concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in conscious, freely moving rats. In addition, we established a method to continuously monitor free corticosterone levels in dialysates. Behavioral activity was scored by measuring the time during which rats were active (locomotion, grooming, eating, drinking). We found a significant, positive relationship between behavioral activity and hippocampal extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300 micrograms/kg body weight) produced an increase in the extracellular concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled by a significant decline in behavioral activity and a marked increase in extracellular corticosterone levels. Thus, the close correlation between hippocampal extracellular 5-HT levels and behavioral activity observed in control rats was disrupted in the LPS-treated animals. The effects of i.p. LPS could be mimicked by i.c.v. application of recombinant human IL-1 beta (hIL-1 beta; 100 ng). i.c.v. pretreatment with the IL-1 receptor antagonist (IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra showed no intrinsic effects. Furthermore, it was found that i.c.v. pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p. LPS-induced (100 micrograms/kg body weight) rise in hippocampal extracellular 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pregnenolone enhances EEG delta activity during non-rapid eye movement sleep in the rat, in contrast to midazolam.

Several endogenous steroids exert their neuroactivity through non-genomic effects and act as potent GABAA receptor-agonists or-antagonists. To examine the influence of the main precursor of these steroids on sleep-wake behaviour, pregnenolone (400 micrograms) was dissolved in oil and administrated s.c. to 8 rats at the beginning of the light period. For comparison, the benzodiazepine midazolam was also injected (3 mg/kg). The effects on the amounts of the vigilance states and on the EEG signals within each state were investigated during 24 hours. Compared to control vehicle, pregnenolone did not significantly affect the duration of the vigilance states. However, delta activity (0.5-4 Hz) within non-rapid eye movement sleep (nonREMS) was enhanced throughout the recording period. Midazolam increased nonREMS, decreased wakefulness and, transiently, also suppressed rapid eye movement sleep (REMS). Spectral analysis of the EEG within nonREMS showed a long lasting reduction in delta and theta activity (4-9 Hz) and a shorter lasting enhancement in the higher frequencies (10-25 Hz). EEG activity within REMS and wakefulness was elevated in the higher frequencies (> or = 10 Hz) during the the first half of the recording period. We conclude that in the rat, the effects of midazolam on EEG activity closely resemble those of benzodiazepines in other mammalian species. The influence of pregnenolone on EEG delta activity within nonREMS indicates that pregnenolone acts as an inverse GABAA-benzodiazepine agonist.

Animals↗

Neural encoding of amplitude modulation within the auditory midbrain of squirrel monkeys.

The neuronal responses to amplitude modulated (AM) sounds were investigated in the auditory midbrain of the squirrel monkey. Sinusoidally modulated tones and noise served as acoustic stimuli. In order to describe the response properties of collicular neurons, Fast-Fourier-Transformation (FFT), a cross-correlation algorithm and spike-rate counts were applied to translate the neuronal reactions into modulation transfer functions. FFT and cross-correlation defined a measure for synchronicity of the neuronal discharges with the modulation cycles. All neurons (542) responded selectively to AM-sounds insofar as all displayed a best modulation frequency (BMF). Most of them furthermore had a band-pass-like modulation transfer function, whose center frequencies were mainly between 8 and 128 Hz. Transfer functions obtained by spike-rate showed less selectivity: a relatively great number of neurons did not change their spike rate as a function of modulation frequency. The results show that encoding of amplitude-modulated sounds occurs to a greater extent via phase locking of discharges than via changes in spike number. In the same way, changing modulation depth is processed: whereas spike rate on average remains constant between 100% and 0% modulation, there is a drastic reduction in synchronicity. No clear relationship was found between a unit's characteristic frequency and BMF; the same applied to BMF and recording place. The results furthermore show that amplitude modulations are encoded selectively in a band pass function in a non-human primate. The midbrain thereby occupies an intermediate position within the pathway from the periphery to the cortex. This form of temporal resolution probably underlies mechanisms caused by the increasing synaptic activity in the course of the pathway. This may indicate adaptation since those modulation frequencies embedded in this species' vocal repertoire fit quite well with the system's tuning properties for amplitude modulation.

Acoustic Stimulation↗

Processing of amplitude modulated sounds in the medial geniculate body of squirrel monkeys.

The responses of single and multi units in the medial geniculate body of the squirrel monkey (Saimiri sciureus) to modulation frequency, modulation depth and changes in absolute intensity of sinusoidally amplitude modulated (AM) sounds were studied. Both spike-frequency and spike rate modulation were used as a measure for neuronal response. Spike rate modulation was derived from FFT (Fast-Fourier-Transformation) analysis of the PSTHs. In all cases (N = 133) spike rate modulation was shown to be dependent on the stimulus modulation frequency: Most neurons responded best to one modulation frequency, i.e., they showed a modulation transfer function with bandpass characteristic; only a few displayed a low pass or multiple peaked transfer characteristic. The majority of the neurons responded best in a range from 4 to 64 Hz, with a peak at 32 Hz and a median at 16 Hz. Such modulation frequencies are common in parts of the species vocal repertoire.

Acoustic Stimulation↗

On the mechanisms of call coding through auditory neurons in the squirrel monkey.

The main goal of the study was to investigate the neural processing of those acoustic signals through auditory neurons whose relevance for communication is either obvious or has been tested by psychoacoustic or behavioral experiments. Thus the activity of cortical, thalamic (MGB) and midbrain (IC) neurons of the auditory pathway were studied with periodically amplitude-modulated (AM) sounds, species-specific AM vocalizations and self-produced vocalizations. With regard to the processing of AM stimuli, there is evidence of a neural correlate to the psychoacoustic phenomenon "fluctuation strength": maximum of the Best Modulation Frequency (BMF) for the cortex was registered at 4 Hz. Furthermore, a relatively large number of units within the IC and the MGB can encode such amplitude changes which have been shown to be of communicative function; here too a neural correlate to the encoding processes of species-specific calls was indicated. Self-produced vocalizations do not seem to underlie a specific processing except that in higher auditory structures, they evoke quantitatively lower responses. In the midbrain, such less active areas are rare and were localized in regions belonging more to secondary auditory structures than primary ones.

Animals↗

Searching for neural correlates of the hearing sensation fluctuation strength in the auditory cortex of squirrel monkeys.

Sounds with slow (less than 20 Hz) fluctuations may elicit the hearing sensation fluctuation strength. For AM tones, neural correlates of fluctuation strength were searched in the auditory cortex of unanesthetized squirrel monkeys. To enable a comparison of psychophysical and physiological data, the 'modulation' of the peristimulus time histogram was fitted by a sinusoidal function. The dependence of the amplitude of this function on modulation frequency, modulation depth and sound pressure level was often comparable to the dependence of fluctuation strength on the same stimulus parameters. In particular, as a function of modulation frequency, the neural data also show a bandpass characteristic at low modulation frequencies as was found for the hearing sensation fluctuation strength.

Animals↗

Functional anatomy of the inferior colliculus and the auditory cortex: current source density analyses of click-evoked potentials.

In the auditory midbrain (inferior colliculus) and cortex (superior temporal gyrus) of awake squirrel monkeys profiles of click-evoked field potentials were recorded. The recording tracks were reconstructed anatomically. From the field potentials the one-dimensional current source density (CSD) distributions were calculated. By comparing the CSD profiles with the anatomical features of the reconstructed recording paths, the components of the CSDs could be attributed to certain anatomical sites. Thus a physiological method for the functional identification of recording sites was obtained. It permits the identification of depth locations of specific laminae in cortex. In the inferior colliculus it permits distinction between central and peripheral regions and between three depth segments. The CSDs in the central nucleus of the inferior colliculus lend functional support to the anatomical division into three distinct parts and, in addition, provide the temporal aspects of the main groups of synaptic activities. The CSDs in the auditory cortex permit determination of five different groups of excitatory synaptic activations. The spatio-temporal distributions of these components are very similar to those obtained in other neocortical areas and thus corroborate the hypothesis that afferent activity is relayed very similarly in all sensory areas of neocortex.

Acoustic Stimulation↗

Inhibition of auditory cortical neurons during phonation.

The neuronal activity of the auditory cortex in the squirrel monkey was investigated during phonation in order to study relationships between brain structures involved in phonation and audition. Responses of single cells in the superior temporal gyrus were extracellularly recorded during stimulation by self-produced vocalizations (elicited either through electrical stimulation of the central gray or uttered spontaneously), and by tape-recorded vocalizations played back together with other species-specific cells. More than half of those cells which reacted to the play-back of self-produced vocalizations responded clearly weaker or not at all during phonation. Less than half of the neurons did not differentiate between self-produced and loudspeaker-transmitted vocalizations. It is concluded that brain structures which are activated during phonation exert an inhibitory influence on parts of the auditory cortex, a fact providing evidence of a neuronal feed-forward circuit mechanism within the process of audiovocal communication.

Acoustic Stimulation↗

Anatomical and physiological evidence for a relationship between the 'cingular' vocalization area and the auditory cortex in the squirrel monkey.

With the aid of the autoradiographic tracing technique the projections from cortical limbic vocalization areas to the auditory cortex in the superior temporal gyrus were studied in the squirrel monkey. The vocalization areas were identified by exploring the anterior limbic cortex with moving electrodes until a site was found where electrical stimulation yielded vocalization. Projections from the region around the cingulate sulcus and supracallosal anterior cingulate gyrus have their terminal fields in the lower part of the superior temporal gyrus (STG) and upper bank of the superior temporal sulcus. Injections just in front of the genu of the corpus callosum and in the subcallosal gyrus and gyrus rectus lead to terminal fields in the middle part of STG. No projections were found in the upper part of STG, i.e. the primary auditory cortex. To test the functional properties of this pathway, action potentials of single neurons in the auditory cortex were recorded during electrical stimulation of the cingular vocalization area. From a total of 135 STG neurons, an effect on spontaneous activity was seen in 27 cells. All except one of these neurons also reacted to acoustic stimuli. In most cases, stimulation of the cingular area caused a decrease in the discharge rate of the STG neurons. In 4 neurons, stimulation of the vocalization area had an influence on the acoustic reactivity of the STG neurons. The results provide evidence that during phonation the 'cingular' vocalization area exerts a predominantly inhibitory influence on auditory cortex neurons. This effect probably is mediated via the extreme capsule. Its possible function is discussed.

Animals↗

Response variability of auditory cortex cells in the squirrel monkey to constant acoustic stimuli.

Sixty-three cells in the superior temporal gyrus of awake squirrel monkeys were tested with 8 species-specific vocalizations plus noise, clicks and tones. Identical series of stimuli were repeatedly presented over 1-5 hour intervals. The responses elicited by both vocalizations and artificial stimuli in primary and secondary cortical neurons often varied over time. In several cases the selectivity of a cell to specific vocalizations appeared to change, i.e., a vocalization which was effective in eliciting a response at one point in the experiment, later became ineffective. In the primary cortex 50% of the cells gave variable responses to one or more of the vocalizations. Twenty percent of the primary cortical cells appeared to change the selectivity of their responses to specific vocalizations. In the secondary cortex 62% of the cells varied in their responses to vocalizations; 42% showing apparent changes in selectivity.

Acoustic Stimulation↗

Convergent projections of different limbic vocalization areas in the squirrel monkey.

The projections of four different sub-areas within the anterior limbic cortex, all yielding vocalization when electrically stimulated, were compared in six squirrel monkeys by the autoradiographic tracing technique. Areas of convergence of the projections from all four vocalization loci were the cortex within the anterior cingulate sulcus, a zone following the inferior thalamic peduncle from the central amygdaloid nucleus through the substantia innominata into the midline thalamus, a second zone following the periventricular fibre system from the anterior diencephalon to the caudal midbrain and dorsolateral pontine tegmentum and, finally, the tail of the caudate nucleus. Except for the latter, all of these brain structures produce vocalization when electrically stimulated. The call types elicitable from these projection areas are sometimes different from those elicitable from the anterior limbic cortex. It is hypothesized that the anterior limbic cortex controls vocalization directly, independently of the specific motivational state underlying it.

Animals↗

Projections from the 'cingular' vocalization area in the squirrel monkey.

In 5 squirrel monkeys the anatomical projections from the 'cingular' vocalization area were studied by the autoradiographic tracing technique. The 'cingular' vocalization area lies around the sulcus cinguli at the level of the genu of the corpus callosum; its electrical stimulation yields purring and cackling calls. The following efferent connections were found: corticocortical fibers could be traced into the orbital cortex (areas 10 and 11), dorsomedial frontal cortex (areas 9, 8 and 6), limbic cortex (areas 25, 24 and 23), Broca's area (area 44), frontal operculum (area 50), insula (areas 13 and 14), and auditory association cortex (area 22). Subcortical terminal fields within the telencephalon were found in the nucleus caudatus, putamen, claustrum, globus pallidus, olfactory tubercle, preoptic region and nucleus centralis and basolateralis amygdalae. Fibers reached most of these structures along different trajectories. In the diencephalon terminal fields lay in the dorsal hypothalamus, the subthalamus, lateral habenular nucleus, and the following thalamic nuclei: nucleus reticularis, ventralis anterior, centralis medialis, centralis superior lateralis, centralis inferior, submedius, medialis dorsalis and centrum medianum. In the midbrain, the periaqueductal gray was the only projection area, extending into the parabrachial nuclei at the pontomesencephalic transition. The most caudal terminal field was found in the medial pontine gray. No terminals were detected in the nucleus ambiguus, nucleus n. hypoglossi or in any other cranial motor nucleus involved in phonation processes. A comparison of this projection system with the whole of structures producing vocalization when electrically stimulated yielded only partial overlap. Not all vocalization areas lie within the 'cingular' projection system, and inversely, not the whole projection system yielded vocalization. Overlap took place in the anterior limbic cortex, preoptic region, central amygdaloid nucleus, midline thalamus, dorsal hypothalamus, periaqueductal gray and parabrachial nuclei. These structures are considered to compose a functionally coherent vocalization system. The projections into Broca's area, nucleus ventralis anterior thalami, frontoopercular cortex within the lateral fissure, pontine nuclei and superior temporal gyrus are discussed in their possible relationship to vocalization processes.

Animals↗