A neural cocktail-party processor

Sensory segmentation is an outstanding unsolved problem of theoretical, practical and technical importance. The basic idea of a solution is described in the form of a model. The response of neurons within the sensory field is temporally unstable. Segmentation is expressed by synchronization within segments and desynchronization between segments. Correlations are generated by an autonomous pattern formation process. Neuronal coupling is the result both of peripheral evidence (similarity of local quality) and of central evidence (common membership in a stored pattern). The model is consistent with known anatomy and physiology. However, a new physiological function, synaptic modulation, has to be postulated. The present paper restricts explicit treatment to the peripheral evidence represented by amplitude modulations globally present in all components of a sound spectrum. Generalization to arbitrary sensory qualities will be the subject of a later paper. The model is an application and illustration of the Correlation Theory of brain function.This work has been supported by Grant I/37-821 of the Stiftung Volkswagenwerk.     

The inhibitory chloride channel activated by glutamate as well asγ-amino-butyric acid (GABA)

Summary Outside-out and inside-out patches of membrane were excised from different muscles of crayfish (Austropotamobius torrentium) and single channel currents elicited by synaptic transmitters and their analogues were measured with the patchclamp technique. If the Cl^–-concentration was high on both sides of the membrane, glutamate even at concentrations <1 M elicited low amplitude single channel currents, which were identified to be Cl^–-currents. The same channels were also activated by 10 M GABA. Glutamate and GABA showed competition in activating these inhibitory channels. Amplitude histograms of the single channel currents presented well defined peaks corresponding to 3 channel substatesI ₁,I ₂ andI ₃, with conductances of about(I₁)=22 pS in high chloride corresponding to a permeability _Cl(I₁)=3.5× 10^–14 cm³/s),(I₂)=2(I₁) and(I₃)=3(I₁). Glutamate activated preferably stateI ₁, and GABA stateI ₂, but both could activate all states at sufficient concentration. Distributions of the open times in the different states were plotted and could be fitted each with one or two exponentials described by time constants of(I₁) of 1 and 6 ms,(I₂) of 2 to 3 ms, and(I₃) or 1 to 2 ms. The burst durations had components of 3 to 4 and of 30 to 40 ms. All these durations were approximately the same when the channels were activated by glutamate and GABA. The analogue quisqualate of glutamate, as well as the GABA analogue-guanidino propionic acid also elicited the respective patterns of states of the inhibitory channel. Quisqualate is by far the most effective agonist and glutamate is more effective than GABA at the inhibitory receptor. Picrotoxin blocked activation of the inhibitory channel by GABA more effectively than by glutamate. The importance of the activation of the inhibitory channel by glutamate as well as by GABA and their analogues is discussed. Elements of a tentative reaction schema are proposed.     

Immunohistochemical localization of neuropeptide Y in the guinea pig medulla oblongata

Summary The immunohistochemical localization of neuropeptide Y (NPY) was correlated with those of dopamine--hydroxylase (DBH) and vasoactive intestinal polypeptide (VIP) by mapping serial 7 m paraffin sections at three levels of the guina pig lower brainstem: a) area postrema, b) dorsal motor nucleus of the vagus, and c) nucleus prepositus of the hypoglossal nerve. Based on differences in transmitter expression, three populations of NPY-immunoreactive (IR) neurons were distinguished: NPY-IR catecholaminergic cells (NPY/CA), NPY-IR VIP-ergic cells (NPY/VIP), and NPY-IR cells which were not reactive to either DBH or VIP. Within these populations, size differences among neurons in characteristic locations allowed differentiation among the following subpopulations: NPY/CA neurons in the lateral reticular nucleus — magnocellular part (mean neuronal size 538 m²) and parvocellular part (318 m²)-, in the vagus-solitarius complex (433 m²), and in the dorsal strip (348 m²); NPY/VIP neurons in the vagus-solitarius complex (368 m²) and in the nucleus ovalis (236 m²). Apart from scattered NPY-IR cell bodies in the regions listed above, NPY-IR cell bodies in the lateral portion of the nucleus solitarius and in the caudal part of the spinal nucleus of the trigeminal nerve did not exhibit IR to either DBH or VIP. NPY-IR neurons in the area postrema occurred too infrequently for co-localization studies. The differential distribution of heterogeneous NPY-IR cell subpopulations may reflect the involvement of NPY in a variety of neuronal functions.Supported by the Deutsche Forschungsgemeinschaft, grant He 919/6-1     

Interaction of medroxyprogesterone acetate with cytosol androgen receptors in the rat hypothalamus and pituitary

The binding of medroxyprogesterone acetate (MPA) with cytosol androgen receptors from rat pituitary and hypothalamus was studied. The pituitary and hypothalamic cytosol androgen receptors from adult castrated female rats were in vitro labeled using 3H natural (testosterone (T) and 5 alpha-dihydrotestosterone (DHT] and [3H]synthetic (methyltrienolone) androgens as radioligands. The [3H]androgen-receptor complexes sedimented with a coefficient of 8S in linear sucrose gradients. When incubated with an excess of radioinert MPA, specific binding was abolished indicating interaction of MPA with androgen receptors. Furthermore specific [3H]MPA-androgen cytosol receptor complexes could be identified in these neuroendocrine tissues when a post-gradient receptor labeling technique was used in the absence or presence of radioinert MPA, DHT, and triamcinolone acetonide. A study of binding kinetics disclosed that the equilibrium dissociation constant and saturation binding capacity for the MPA binder, were similar to those exhibited by DHT binding to androgen receptors in both studied tissues under identical experimental conditions. The overall results were interpreted as demonstrating that MPA interacts with cytosol steroid receptors other than those of progesterone in the rat hypothalamus and anterior pituitary. The data are consistent with MPA binding to androgen receptors.     

Morphometrisch-ultrastrukturelle Untersuchungen am Nucleus supraopticus der Ratte nach Dehydratation

Zusammenfassung Der Nucleus supraopticus der Ratte, die einer Dehydratation ausgesetzt war, wurde ultrastrukturell-morphometrisch analysiert. Dabei zeigte sich, daß die relativen Volumenanteile der einzelnen Zellkompartimente während der fünftägigen Durstperiode eine auffallende Konstanz aufweisen. Hingegen läßt sich eine absolute Zunahme der Einzelzellvolumina und somit auch der an der Synthese und Sekretion der Neurohormone beteiligten Zellkompartimente feststellen. Die vorliegenden Befunde sprechen für einen beschleunigten Abtransport des neurosekretorischen Materials bei gesteigerter Synthese. Auf eine optimale Standardisierung der Perfusionsmethode bei Untersuchungen am neurosekretorischen Zwischenhirnsystem wird hingewiesen.

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Morphometric-ultrastructural investigations on the supraoptic nucleus of dehydrated rats

Summary The supraoptic nucleus of the dehydrated rat has been analysed by electron microscopy and morphometry. With that it appears, that the relative volumes of the different cell compartments are striking constant. Otherwise one can see an absolute increase of the cell volume together with the cell compartments which take part at the synthesis and secretion of the neurohormones. These results are expression of an accelerated move of the neurosecretory material during increased synthesis. The importance of an optimal standardization of the perfusion-method in investigations of the neurosecretory system is demonstrated.

Wesentliche Teile der vorliegenden Arbeit werden von H. F. Reinhardt der Medizinischen Fakultät der Universität Basel als Dissertation vorgelegt.     

Histochemical studies on the lipids in the epithelium of the fetal colon

Summary Large intestines from 30 fetuses with crown-rump lengths ranging from 26 to 180 mm have been studied histochemically as to their epithelial content of lipids. These lipids have been localized intracellularly and basally in the cells, and comparative studies of the colon and the small intestine have demonstrated that there are considerable amounts of lipids in the colon as compared with the small intestine.It is concluded that the main part of the lipids consist of saturated and unsaturated constituents.The possible explanations of the lipids as absorbed material, biological active material synthetized de novo or as material involved in the metabolism of fetal surface cells are discussed.This work was supported by a grant from the Aid of the Crippled Children, New York.     

Auerbach's plexus of mammals and man: Electron microscopic identification of three different types of neuronal processes in myenteric ganglia of the large intestine from rhesus monkeys,guinea-pigs and man

Summary Ganglia from Auerbach's plexus of the large intestine (caecum, appendix vermiformis, colon transversum and rectum) in man, rhesus monkey and guinea-pig are composed of nerve cells and their processes, typical Schwann cells and a vast neuropil. The neuropil consists of dendrites and axons of intrinsic nerve cell perikarya and axons of extrinsic neurons. Axonal profiles in large nerve fibre bundles are of uniform size and appearance, embedded in infoldings of Schwann cell cytoplasm and contain occasional large granular vesicles, mitochondria and neurotubules. Preterminal axons widen into vesicle filled varicosities, some of which establish synaptic contact with intrinsic nerve cell bodies.At least three different types of neuronal processes can be distinguished in the myenteric neuropil according to the size, appearance and commutual proportion of vesicles present in axonal varicosities, and their ability to accumulate exogenous 5- and 6-hydroxydopamine and 5-hydroxydopa: 1. Axonal enlargements containing a major population of small electron lucent synaptic vesicles (350–600 Å in diameter) together with a small number of membrane-bound, opaque granules (800–1,100 Å). These profiles have been identified as cholinergic axons. The boutons establish synaptic contacts with dendritic processes of intrinsic nerve cell bodies; membrane specializations are found at the preand postsynaptic sites. 2. Axonal beads of sometimes very large diameter, containing an approximately equal amount of large granular vesicles (850–1,600 Å) and small, electron lucent or faintly opaque vesicles (400–600 Å). The granular core of the large vesicles is of medium electron density and may either fill the entire vesicle or is separated from the limiting membrane by a more or less clear interspace. The fibres probably belong to intrinsic neurons, and because of the similarity of the large, membrane-bound vesicles with neurosecretory elementary granules, they have been designated p-type fibres (polypeptide fibres). The granular core of the vesicles in these fibres becomes more electron dense after treatment with 5-OH-dopa. The accumulation of an amine precursor analogue in combination with a possible storage of a polypeptide substance (or an ATP-like substance) resembles the situation in several diffusely distributed endocrine cell systems. 3. Varicosities of axons equipped with small (400–600 Å) empty or sometimes granular vesicles, medium sized (500–900 Å) vesicles with highly electron dense cores and occasional large (900–1,300 Å) granular vesicles. Pretreatment with 5-OH-dopamine increases the electron density in almost all medium-sized granular vesicles and some of the large granular vesicles; an osmiophilic core develops in some small vesicles. 6-hydroxydopamine results in degenerative changes in the varicosities of this type of neurons. Concomitantly, both catecholamine analogues markedly reduce neuronal noradrenaline in the large intestine, as demonstrated by fluorescence histochemistry and in fluorimetric determinations. The ultrastructural features of these varicosities and their reaction to 5- and 6-OH-dopamine indicate that they belong to adrenergic, sympathetic nerves. No membrane specializations could be detected at sites of close contact of the adrenergic boutons with dendrites and cell bodies of intrinsic nerve cells.Supported by grants from the Deutsche Forschungsgemeinschaft.Supported by a grant from Albert Pahlsson's Foundation, Sweden. The work was carried out within a research organization sponsored by the Swedish Medical Research Council (projects No. B70-14X-1007-05B, B70-14X-712-05, and B70-14X-56-06).