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Background gamma-oscillations in neuronal networks with interhemisphere connections.

Results obtained in studies of the high-frequency components of EEG recordings and in modeling, determining the conditions for the appearance of gamma oscillations in interneuronal interactions, were compared with features of the background gamma oscillations recorded in the activity of interacting neurons located in symmetrical loci of the right and left hemisphere motor areas in anesthetized rats. Similarities in high frequencies extracted from EEG recordings and in the most commonly observed gamma oscillation frequencies suggested that these oscillations may represent one of the mechanisms underlying the high-frequency EEG component. Published modeling data indicating that the formation of these oscillations involves reciprocal inhibitory connections, along with our own data that interhemisphere oscillations are seen 1.5 times more commonly than ipsilateral oscillations, suggested that transcallosal inhibition is more effective than inhibition between neighboring cells. Simultaneously extracted background oscillations in the interacting activity of callosal cells and neighboring cells could be different, as could those characterizing the activity of individual neurons. It is suggested that these differences underlie the functional heterogeneity of local cortical neuronal networks and explain the fact that these networks contain various types of inhibitory neurons.

Animals↗

A role for subplate neurons in the patterning of connections from thalamus to neocortex.

During cerebral cortical development, ingrowing axons from different thalamic nuclei select and invade their cortical targets. The selection of an appropriate target is first evident even before thalamic axons grow into the cortical plate: initially axons accumulate and wait below their cortical target area in a zone called the subplate. This zone also contains the first postmitotic neurons of the cerebral cortex, the subplate neurons. Here we have investigated whether subplate neurons are involved in the process of target selection by thalamic axons by ablating them from specific cortical regions at the onset of the waiting period and examining the subsequent thalamocortical axon projection patterns. Subplate neurons were ablated at the onset of the waiting period by intracortical injections of kainic acid. The effect of the ablation on the thalamocortical projection from visual thalamus was examined by DiI-labeling of the LGN days to weeks following the lesion. At two to four weeks post-lesion, times when LGN axons would have normally invaded the cortical plate, the axons remained below the cortical plate and grew past their appropriate cortical target in an anomalous pathway. Moreover, examination of LGN axons at one week post-lesion, a time when they would normally be waiting and branching within the visual subplate, indicated that the axons had already grown past their correct destination. These observations suggest that visual subplate neurons are involved in the process by which LGN axons select and subsequently grow into visual cortex. In contrast, subplate neurons do not appear to play a major role in the initial morphological development of the LGN itself. Subplate ablations did not alter dendritic growth or shapes of LGN projection neurons during the period under study, nor did it prevent the segregation of retinal ganglion cell axons into eye-specific layers. However, the overall size of the LGN was reduced, suggesting that there may be increased cell death of LGN neurons in the absence of subplate neurons. To examine whether subplate neurons beneath other neocortical areas play a similar role in the formation of thalamocortical connections, subplate neurons were deleted beneath auditory cortex at the onset of the waiting period for auditory thalamic axons. Subsequent DiI labeling revealed that in these animals the majority of MGN axons had grown past auditory cortex instead of innervating it. Taken together these observations underscore a general requirement for subplate neurons throughout neocortex in the process of cortical target selection and ingrowth by thalamic axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Connections from upper cervical inspiratory neurons to phrenic and intercostal motoneurons studied with cross-correlation in the decerebrate rat.

We examined the synaptic connections from upper cervical inspiratory neurons to phrenic and intercostal motoneurons in decerebrate rats using cross-correlation. Upper cervical inspiratory neurons (n = 79) were recorded from the C1 and C2 segments of the spinal cord in 38 vagotomized, paralyzed, ventilated, and decerebrate rats. The neurons were identified by their inspiratory firing pattern and antidromic activation from the ipsilateral spinal cord at C7. Whole-nerve recordings were made using bipolar electrodes from the central cut ends of the C5 phrenic nerve and the external and internal intercostal nerves at various thoracic levels. Cross-correlation histograms were computed between these recordings to detect short time-scale synchronizations indicative of synaptic connections. The 55 cross-correlation histograms computed between the upper cervical inspiratory neurons and the ipsilateral phrenic nerve showed seven (13%) narrow peaks (mean half-amplitude width +/- SD, 1.09 +/- 0.15 ms) at short latencies (mean latency +/- SD, 1.29 +/- 0.26 ms) suggestive of monosynaptic excitation, and four (7%) broader peaks (mean half-amplitude width +/- SD, 1.50 +/- 0.17 ms) at short latencies (mean latency +/- SD, 1.40 +/- 0.24 ms) suggestive of oligosynaptic excitation. Another 14 (25%) cross-correlation histograms displayed a central broad peak (mean half-amplitude width +/- SD, 1.59 +/- 0.23 ms) suggestive of common activation. The eight cross-correlation histograms computed between the upper cervical inspiratory neurons and the contralateral phrenic nerve were featureless. The 77 cross-correlation histograms computed between the upper cervical inspiratory neurons and the internal and external intercostal nerves at various thoracic levels (T2-8) showed no peaks suggestive of synaptic connections. We conclude that some upper cervical inspiratory neurons make monosynaptic and paucisynaptic connections to phrenic motoneurons but not to intercostal motoneurons.

Animals↗

[Neuronal composition and interneuronal connections of field 5 of the parietal association cortex of cats].

Field 5 of the cat neocortex was studied by the Golgi method. Characteristic features here are as follows: predominance of pyramidal cells in layers II-III and existence of large forms (40X26 micron) among them; single and clustered giant pyramidal neurons (70X23 micron) in layer V; large (25-30 micron in diameter) and giant (40-45 micron in diameter) stellate cells with radial dendrites, single or gathered in groups, in layers V--VI; few efferent spindle-like neurons (40X20 micron) in layers V-VI. Stellate cells found in layers II-VI probably unite the pyramidal cells localized within one or several layers. Some of the stellate cells in layers II-III establish long horizontal connections within the field. Interneuronal connections are formed by axo-somatic and axo-dendritic terminals with the prevalence of the latter; dendro-dendritic and axo-axonic contacts were rarely observed.

Animals↗

Neuronal circuitry and synaptic connectivity of the basal ganglia.

The concept of organization of the basal ganglia has changed markedly over the last 10 years. These developments have led to the introduction of a schematic model of the functional circuitry of the basal ganglia that accounts for normal and abnormal basal ganglia functions. The recent introduction of powerful techniques for the analysis of neuronal networks has led to many new developments in our understanding of the anatomic and synaptic organization of the basal ganglia. The objective of this article is to go from the established model of the basal ganglia connectivity to new anatomic findings that lead to reconsideration and refinement of some aspects of the models.

Basal Ganglia↗

Ultrastructural and functional connectivity of intracellularly stained neurones in the vertebrate retina: correlative analyses.

A variety of intracellular recording and staining techniques has been used to establish structure-function and, in some cases, structure-function-neurochemical correlations in fish, turtle, and cat retinae. Cone photoreceptor-horizontal cell connectivity has been studied extensively in the cyprinid fish retina by intracellular staining with horseradish peroxidase (HRP) and subsequent electron microscopy. The available data suggest that horizontal cell dendrites around the ridge of the synaptic ribbon are postsynaptic, whilst finger-like extensions ("spinules") of lateral dendrites function as inhibitory feedback terminals. An interesting feature of this interaction is its plasticity: the feedback pathway is suppressed in the dark and becomes potentiated by light adaptation of the retina. Intracellular recordings and stainings of ganglion cells in both turtle and cat retinae have been possible. Prelabelling of ganglion cells by retrograde transport of rhodamine from the tectum allows ganglion cells to be stained under visual control, and their synaptic inputs determined by electron microscopy. Such studies have been extended to double labelling by using autoradiography or postembedding immunohistochemistry to identify the neurotransmitter content of the labelled cell and/or the neurotransmitter(s) converging upon it. It is envisaged that further applications of intracellular staining followed by double- or even triple-labelling will continue to enhance greatly our understanding of the functional architecture of the vertebrate retina.

Animals↗

Functional connectivity between brain stem midline neurons with respiratory-modulated firing rates.

1. Recent evidence supports the idea that neurons distributed along the midline of the brain stem contribute to the regulation of breathing. This study sought evidence for functional connections between midline neurons with respiratory-modulated firing rates. 2. Experiments were conducted on 38 anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Planar arrays of tungsten microelectrodes were used to monitor spike trains of two or more midline neurons simultaneously in the regions of n. raphe obscurus, n. raphe pallidus, and n. raphe magnus. Efferent phrenic nerve activity was recorded. Data were analyzed with auto- and cross-correlograms and cycle-triggered histograms. Spike trains of neurons were also tested for respiratory modulation by an analysis of variance with the use of a subjects-by-treatments experimental design. 3. Of 584 neurons studied, 99.1% were tonic, i.e., they had firing probabilities greater than zero in all phases of the respiratory cycle. Fifty-three percent of the neurons had respiratory-modulated firing rates; 223 cells were more active during the expiratory (E) interval; 88 neurons were inspiratory (I)-related. The remaining cells were classified as having no respiratory-related modulation of firing rate (NRR). 4. The spike trains of 210 of 1,078 pairs (19.5%) of brain stem midline neurons exhibited short-time scale correlations indicative of paucisynaptic interactions. Primary cross-correlogram features included 129 central peaks, 45 offset peaks, two central troughs, and 57 offset troughs. Twenty-two of the neuronal pairs analyzed had both offset peaks and troughs. Correlograms from an additional 35 pairs of neurons had multiple peaks and troughs without a significant primary feature. 5. The frequency of correlations for neuron pairs composed of cells with respiratory-modulated firing rates was as follows: E-E, 40/185 (22%); E-I, 23/111 (21%); E-NRR, 45/297 (15%); I-I, 11/25 (44%); and I-NRR, 13/104 (13%). Twenty-two percent of the NRR pairs (79/357) exhibited short-time scale correlations. 6. Thirty pairs of neurons included a cell with an antidromically identified axonal projection extending to at least the third cervical segment. The mean estimated conduction velocity based on the single-site stimulation method was 26.5 +/- 9.9 (SD) m/s. 7. The results provide evidence for inhibitory and excitatory functional connections between midline brain stem neurons. Data support the hypothesis that the respiratory-modulated discharge patterns of midline neurons are, at least in part, a consequence of the synaptic actions of other midline cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

[Reactions of a neuronal network model with stochastic connections to frequency variations and interval structure of input signals].

A computer model of neuron network with stochastic ally organized connections was studied. The constructed neural network found to be highly sensitive to the interval structure of input signals and is capable of integrating and encoding them by the ratio of frequencies of pulsations of neurons comprising the network. The results obtained suggest that essential in modelling real brain structures is both the stochastic distribution of interneuron connections and specific configuration of anatomic connections of the real neural network. The proposal is made to assess these two possibilities separately.

Computer Simulation↗

Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study.

In adult rats with a unilateral 6-hydroxydopamine-induced destruction of the nigrostriatal dopamine (DA) pathway, grafts of embryonic substantia nigra can establish a new dopaminergic terminal fiber plexus in the previously denervated neostriatum and compensate for some of the behavioral deficits induced by the nigrostriatal lesion. In the present study the synaptic connections of the ingrowing DA fibers from the graft were analyzed ultrastructurally, using immunocytochemical localization of tyrosine hydroxylase (TH), in animals whose lesion-induced motor asymmetry had been completely compensated for by the nigral grafts. In two of the animals, horseradish peroxidase-wheatgerm agglutinin conjugate was injected into the graft in order to trace possible reciprocal afferent connections to the graft from the host striatum. TH-immunoreactive axons from the graft were seen to make abundant symmetric synapses with neuronal elements in the host neostriatum. Between 85 and 90% of these synapses were on dendritic shafts and spines, and the rest were on neuronal perikarya. Two principal targets were identified: dendrites of spiny neurons, the majority of which are likely to be striatal projection neurons; and the cell bodies of giant neurons, most (or perhaps all) of which are known to be cholinergic interneurons. The synapses made on dendritic spines, which constituted about 40% of all TH-positive synapses formed by the TH-positive neurons in the graft, resembled those seen in normal animals, both in that they made contacts with spine necks and in that they invariably were associated with an asymmetric TH-negative synapse contacting the spine head. The innervation of the giant cell perikarya, which constituted about 6% of all TH-positive synapses found, was strikingly abnormal in that the graft-derived TH-positive fibers formed dense pericellular "baskets" selectively around the giant cell bodies. Such arrangements were never seen in the normal striatum, nor did they occur in the intact contralateral striatum in the grafted animals. It is proposed that this apparent dopaminergic hyperinnervation from the graft could provide a powerful inhibition of the cholinergic interneurons in the reinnervated host striatum, and that such an inhibitory mechanism could assist in the graft-induced functional recovery by potentiating the functional effects of DA synapses terminating on the spiny efferent neurons. This dual innervation may thus help to explain why restoration of only a small proportion of the striatal DA innervation by the graft is sufficient to induce complete compensation of, e.g., motor asymmetry in the lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Inhibitory connections among rostral medullary expiratory neurones detected with cross-correlation in the decerebrate rat.

Expiratory neurones, with a decrementing firing pattern during the first phase of expiration (E-DEC) and located in the rostral ventrolateral medulla, are thought to be involved in the network generating respiratory rhythm, which also includes expiratory neurones with augmenting firing patterns (E-AUG). We used cross-correlation to detect their synaptic interconnections and connections to phrenic motoneurones in 32 vagotomised, decerebrate, paralysed and ventilated male rats. Pairs of neurones were recorded extracellularly with glass-insulated tungsten microelectrodes and the whole phrenic nerve with bipolar silver wire electrodes. Of the 79 cross-correlograms computed between pairs of E-DEC neurones, 8 (approximately 10%) showed evidence for inhibitory connections. Of the 67 cross-correlograms computed between E-DEC and E-AUG neurones, 5 (7.5%) showed evidence for a monosynaptic inhibition of the E-AUG neurone by the E-DEC neurone, while 3 (4.5%) showed evidence for a monosynaptic inhibition of the E-DEC neurone by the E-AUG neurone. An inhibitory connection from E-DEC neurones to phrenic motoneurones was detected in 5 (approximately 2%) of the cross-correlograms, and from E-AUG neurones to phrenic motoneurones in 4 (approximately 3.7%). These results are the first demonstration that network models of rhythm generation in the rat involving reciprocal inhibition between E-DEC and E-AUG neurones could have a neurophysiological basis, and the first to demonstrate that phrenic motoneurones are inhibited during the early phase of expiration by E-DEC neurones.

Animals↗

Electron microscopical observations on the indoleamine-accumulating neurons and their synaptic connections in the retina of the cat.

The distribution of indoleamine-accumulating amacrine cells and their synaptic connections in the retina of the cat were analyzed in the fluorescence, phase-contrast, and electron microscopes. The findings were compared to recently characterized morphological subclasses of amacrine cells. The indoleamine-accumulating neurons were visualized after labeling with an exogenous indoleamine, 5,6-dihydroxytryptamine. The intravitreal injection of the labeling drug was preceded by treatment with the neurotoxic dopamine-analogue, 6-hydroxydopamine, in order to destroy the otherwise interfering dopaminergic processes. The analysis in the fluorescence and phase-contrast microscopes confirmed earlier reports that the indoleamine-accumulating cell bodies and processes have a redistribution consistent with that of amacrine cells. A stratified branching pattern of the indoleamine-accumulating processes in the outer half of the inner plexiform layer was discovered. In the inner half of that layer the branching pattern is diffuse. In the electron microscope the indoleamine-accumulating neurons were seen to have synapses fo the conventional type. Their main synaptic contacts are reciprocal synapses with rod bipolar terminals in sublamina b of the inner plexiform layer. They also have synapses with flat cone bipolar terminals in sublamina a, and occasionally with amacrine cells and ganglion cells throughout the inner plexiform layer. Synapses with invaginating cone bipolar terminals, in sublamina b, appear to be rare. The synaptic arrangement with reciprocal synapses with rod bipolar terminals is similar to that of the recently reported AI amacrine cells. It is also similar to that of the indoleamine-accumulating neurons in the retinae of other mammals investigated earlier.

5,6-Dihydroxytryptamine↗

Inhibitory connections between antagonistic motor neurones of the crayfish walking legs.

The inhibitory relationship between two antagonistic groups of motor neurones (MNs) that control the second leg joint of the crayfish Procambarus clarkii, was investigated in an in vitro preparation of the ventral nerve cord. Paired intracellular recordings were used to test the hypothesis that reciprocal inhibitory connections between levator (Lev) and depressor (Dep) MNs are direct. The injection of depolarising current into a Lev MN induces a hyperpolarising response in the Dep MN. This inhibitory relationship does not require spikes in the presynaptic MN, because it persists when spikes are suppressed by the sodium channel blocker tetrodotoxin (TTX). This reciprocal inhibition is graded, and both the amplitude and the time constant of the hyperpolarising response increase with increasing amount of depolarising current injected into an antagonistic MN. Although this inhibition is slow (synaptic delay around 10 ms), it is probably supported by a direct glutamatergic synapse from the antagonistic glutamatergic MN because it persists in the presence of the gamma-amino-butyric acid (GABA) synthesis inhibitor 3-mercapto-propionic acid (3-MPA). This hypothesis is reinforced by the demonstration of close appositions between antagonistic MNs by using a confocal microscope, and by the presence of glutamate-immunoreactive synapses on the neurites of MNs labelled for electron microscopy by intracellular injection of horseradish peroxidase.

3-Mercaptopropionic Acid↗

[Character of functional connections between sensomotor cortex neurons during isolated and combined stimulation of thalamic nuclei].

In experiments on curarized cats pronounced transformations of the "excitatory" component of the "inhibitory-excitatory" dependence of two close neurones in the sensorimotor cortex were found following multiple isolated VPL and VL stimulation. The effects of repetitive stimulation of thalamic nuclei were opposite to each other: VPL stimulation mainly weakened the "excitatory" component of the "inhibitory-excitatory" connection, whereas VL stimulation generally enhanced it. In the course of combined stimulations of both nuclei the character of interneuronal relations, established under the influence of isolated stimuli, showed further changes. Modifications of interneuronal dependence, resulting from thalamic stimulation, could last for several minutes after cessation of all stimulations.

Animals↗

The connectivity of the brain: multi-level quantitative analysis.

We develop a mathematical formalism or calculating connectivity volumes generated by specific topologies with various physical packing strategies. We consider four topologies (full, random, nearest-neighbor, and modular connectivity) and three physical models: (i) interior packing, where neurons and connection fibers are intermixed, (ii) sheeted packing where neurons are located on a sheet with fibers running underneath, and (iii) exterior packing where the neurons are located at the surfaces of a cube or sphere with fibers taking up the internal volume. By extensive cross-referencing of available human neuroanatomical data we produce a consistent set of parameters for the whole brain, the cerebral cortex, and the cerebellar cortex. By comparing these inferred values with those predicted by the expressions, we draw the following general conclusions for the human brain, cortex, and cerebellum: (i) Interior packing is less efficient than exterior packing (in a sphere). (ii) Fully and randomly connected topologies are extremely inefficient. More specifically we find evidence that different topologies and physical packing strategies might be used at different scales. (iii) For the human brain at a macro-structural level, modular topologies on an exterior sphere approach the data most closely. (iv) On a mesostructural level, laminarization and columnarization are evidence of the superior efficiency of organizing the wiring as sheets. (v) Within sheets, microstructures emerge in which interior models are shown to be the most efficient. With regard to interspecies similarities and differences we conjecture (vi) that the remarkable constancy of number of neurons per underlying square millimeter of cortex may be the result of evolution minimizing interneuron distance in grey matter, and (vii) that the topologies that best fit the human brain data should not be assumed to apply to other mammals, such as the mouse for which we show that a random topology may be feasible for the cortex.

Animals↗