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A monosynaptic connection between identified snail neurons.

Electrophysiological and morphological studies of a monosynaptic connection are performed on specimens of the isolated CNS of the snail Achatina fulica, using the standard techniques of intracellular leading-off and neuron stimulation and intracellular pressure injection of cobalt chloride. The presence of a monosynaptic connection between two identified neurons is demonstrated both in the physiological experiment and by means of the intracellular dye.

Action Potentials↗

Central noradrenergic neurons: the autonomic connection.

Most CNS noradrenergic (NE) cell groups reside in portions of the medulla oblongata primarily involved in autonomic control (A1, A2, A5) and even the pontine locus coeruleus (A6) receives a major innervation from these medullary areas. This review examines the neuroanatomical and neurophysiological literature relevant to the issue of the role of CNS NE neurons in central autonomic control (with emphasis on cardiovascular control). It is concluded that NE cells, with the possible exception of certain A5 and A1 neurons, have relatively weak or no inputs from visceral cardiovascular afferents but provide a complex "open loop" control over non-aminergic circuits which are more specialized in the processing of cardiovascular and other autonomic reflexes. The question of whether the C1 "adrenergic" cells of the rostral medulla oblongata actually use noradrenaline as a neurotransmitter is also briefly addressed.

Adrenergic Fibers↗

Dynamic properties of recurrent inhibition in primary visual cortex: contrast and orientation dependence of contextual effects.

A fundamental feature of neural circuitry in the primary visual cortex (V1) is the existence of recurrent excitatory connections between spiny neurons, recurrent inhibitory connections between smooth neurons, and local connections between excitatory and inhibitory neurons. We modeled the dynamic behavior of intermixed excitatory and inhibitory populations of cells in V1 that receive input from the classical receptive field (the receptive field center) through feedforward thalamocortical afferents, as well as input from outside the classical receptive field (the receptive field surround) via long-range intracortical connections. A counterintuitive result is that the response of oriented cells can be facilitated beyond optimal levels when the surround stimulus is cross-oriented with respect to the center and suppressed when the surround stimulus is iso-oriented. This effect is primarily due to changes in recurrent inhibition within a local circuit. Cross-oriented surround stimulation leads to a reduction of presynaptic inhibition and a supraoptimal response, whereas iso-oriented surround stimulation has the opposite effect. This mechanism is used to explain the orientation and contrast dependence of contextual interactions in primary visual cortex: responses to a center stimulus can be both strongly suppressed and supraoptimally facilitated as a function of surround orientation, and these effects diminish as stimulus contrast decreases.

Animals↗

Target-induced transcriptional control of dendritic patterning and connectivity in motor neurons by the ETS gene Pea3.

The apposition of axon terminals and dendrites is critical for the control of neuronal activation, but how distinct neuronal subpopulations establish selective dendrite patterns and acquire specific presynaptic inputs remains unclear. Spinal motor neuron (MN) pools project to specific target muscles and are activated by selective synaptic inputs from group Ia proprioceptive afferents (IaPAs). Here, we show that MN pools with radially projecting dendrites respond to sensory stimulation with monosynaptic latency and are strikingly different from MN pools with dendrites that avoid the central gray matter, which are only activated through indirect connections. We provide genetic evidence that the induction of the ETS transcription factor Pea3 by GDNF is essential in two cervical MN pools to control dendrite patterning and selectivity of IaPA connectivity. These findings suggest that target-induced transcriptional programs control MN dendrite orientation and play a crucial role in the establishment of sensory-motor connections in the spinal cord.

Animals↗

The distribution of acetylcholine receptors in chick ciliary ganglion neurons following disruption of ganglionic connections.

Chick ciliary ganglion neurons have nicotinic acetylcholine receptors (AChRs) that mediate primary chemical synaptic transmission through the ganglion. Previous studies have shown that preganglionic denervation reduces the total number of AChRs in the ganglion about 3-fold in 10 d, while postganglionic axotomy reduces AChR levels about 10-fold in 5 d. Since the neurons contain large numbers of intracellular AChRs in addition to the surface AChRs, the present studies were undertaken to determine whether either surface or internal AChR pools are changed selectively by the operations. An anti-AChR monoclonal antibody followed by an HRP-conjugated secondary antibody was used to visualize AChR distributions on neurons in ciliary ganglia 5 d after postganglionic axotomy and 10 d after preganglionic denervation. Ganglia were permeabilized by treatment with saponin to obtain access to intracellular receptors. The results show that the operations do not qualitatively change the subcellular localization of AChRs, but they do alter the levels relative to control ganglia. Axotomy produces substantial declines both in the number of synaptic AChRs and in the number of intracellular AChRs. Denervation produces a significant, though less extensive decline in the number of intracellular receptors while having no detectable effect on the number of synaptic AChRs. Small alterations in receptor distribution would have gone undetected by the present techniques. Regulation of neuronal AChRs differs in several respects from that described for muscle AChRs: presynaptic input appears to be less important for controlling neuronal AChRs, while signals from the postsynaptic target tissue may be essential for maintaining synaptic receptors on the neurons.

Animals↗

Computational inference of the molecular logic for synaptic connectivity in C. elegans.

MOTIVATION: The nematode C. elegans is an ideal model organism in which to investigate the biomolecular mechanisms underlying the connectivity of neurons, because synaptic connections are described in a comprehensive wiring diagram and methods for defining gene expression profiles of individual neurons are now available. RESULTS: Here we present computational techniques linking these two types of information. A systems-based approach (EMBP: Entropy Minimization and Boolean Parsimony) identifies sets of synergistically interacting genes whose joint expression predicts neural connectivity. We introduce an information theoretic measure of the multivariate synergy, a fundamental concept in systems biology, connecting the members of these gene sets. We present and validate our preliminary results based on publicly available information, and demonstrate that their synergy is exceptionally high indicating joint involvement in pathways. Our strategy provides a robust methodology that will yield increasingly more accurate results as more neuron-specific gene expression data emerge. Ultimately, we expect our approach to provide important clues for universal mechanisms of neural interconnectivity.

Animals↗

Functional connectivity of disparity-tuned neurons in the visual cortex.

Different mechanisms have been proposed concerning how disparity-tuned neurons might be connected to produce the signals for depth perception. Here we present neurophysiological evidence providing insight on this issue. We have recorded simultaneously from pairs of disparity-tuned neurons in the cat's striate cortex. The purpose was to determine the relationships between disparity tuning and functional connectivity revealed through neural cross-correlograms. Monosynaptic connections tend to be stronger between pairs of cells with similar disparity tuning. Pairs of complex cells tend to have either similar tuning or nearly opposite tuning with an absence of quadrature relations. Pairs with at least one simple cell do have some nearly quadrature relationships when they are recorded from the same electrode. Coarse-to-fine connections (i.e., the presynaptic cell has lower disparity frequency and larger disparity range) tend to be stronger but less frequent than those of a fine-to-coarse nature. Our results are consistent with a system that produces weighted averaging across cells that are tuned to similar disparities but different disparity scales to reduce false matches.

Action Potentials↗

Intrinsic neurons and neural connections of the pineal organ of the house sparrow, Passer domesticus, as revealed by anterograde and retrograde transport of horseradish peroxidase.

In Passer domesticus, intrapineal nerve cells were labeled by uptake of microiontophoretically administered horseradish peroxidase (HRP). Unipolar nerve cells with a dichotomously branching stem process are the main source of the dominant pinelaofugal component of the pineal tract, whereas multipolar and bipolar neurons appear to represent interneurons. HRP-Labeled nerve fibers are observed in the distal division (end-piece) of the pineal organ; they can be regarded either as processes of intrapineal neurons or projections of pinealopetal axons originating from central neurons. Furthermore, scattered labeled nerve fibers occur in different portions of the pineal stalk. Nerve fibers containing HRP were also demonstrated in the medial and lateral divisions of the habenular complex and in the periventricular layer of the hypothalamus; these axons apparently represent anterogradely labeled pinealofugal elements. On the other hand, retrogradely labeled neurons were found in the medial habenular complex and in the periventricular hypothalamic gray near the paraventricular nucleus, indicating that the pineal organ receives a pinealopetal innervation arising from the central nervous system. Ultrastructurally, the neuropil of the pineal organ of P. domesticus displays single basal processes of pinealocytes containing synaptic ribbons in association with clear synaptic vesicles. Occasionally, conventional synapses were observed the presynaptic terminals of which exhibit granular inclusions. The pineal tract consisting of four to six spatially separated fiber bundles comprises mainly unmyelinated elements accompanied by only few myelinated axons. The functional role of the neural apparatus revealed in the present study is discussed in context with the humoral (hormonal) control of circadian functions; the latter type of activity has been shown to exist in the pineal organ of P. domesticus (Zimmerman 1976).

Animals↗

Reformation in adult rats of functional septo-hippocampal connections by septal neurons regenerating across an embryonic hippocampal tissue bridge.

Implants of embryonic hippocampus, placed into a cavity transecting the septo-hippocampal pathway in adult rats, have previously been shown to promote the regeneration of the lesional septo-hippocampal axons across the cavity. The present study provides electrophysiological evidence that these regenerating acetylcholinesterase-containing axons are able to re-establish atropine-sensitive excitatory synaptic connections in the grafted hippocampus as well as in the dorsal part of the initially denervated host hippocampus, thus demonstrating that intracerebral tissue implants can promote true, functional regeneration across a major tissue defect in the adult mammalian CNS.

Acetylcholinesterase↗

Changes in neurons and interneural connections of the higher sections of the motor system in the progeny of alcoholized male and female rats.

We have studied the effects of long-term alcoholic intoxication of male and female rats on the structural development of the sensory motor cortex and the caudate nucleus in 21-day-old rats (their progeny). Using light microscopy and morphometry we observed a delay in the maturation of neurons and their dendrites, and also dystrophic changes in the nerve structures in the experimental animals. The morphological changes observed show that alcoholic intoxication of parents leads to negative effects on postnatal development of their progeny.

Alcoholism↗

Depression of synaptic connections between identified motor neurons in the locust.

1. The fast extensor tibiae motor neuron makes direct excitatory central connections with the posterior group of flexor tibiae motor neurons in the locust metathoracic ganglion. The flexor group has a slow, a fast, and an intermediate motor neuron. The motor neurons are involved in the motor program for kicking and jumping, the defensive and escape behaviors of the locust. An antidromic action potential in fast extensor tibiae motor neuron (FETi) results in a monosynaptic, glutamatergic excitatory postsynaptic potential (EPSP) in each of the flexor motor neurons. 2. A train of 10 antidromic spikes in FETi at frequencies of 1-20 Hz resulted in depression of the amplitude of the EPSP in each of the flexor motor neurons. The depression was not significantly different in the different flexor motor neurons. The depression was greater with higher frequency stimulation and was reduced in low calcium saline. 3. After stimulation at 20 Hz, the EPSP amplitude was depressed by approximately 80%. This did not change when the number of stimuli was increased to 20, when stimulation was done in high calcium saline, or when the frequency of stimulation was increased to 50 or 100 Hz. The recovery from depression was greater after 20-Hz stimulation than at lower frequencies, although the recovery was reduced when the number of stimuli was increased, and also in high calcium saline. 4. In normal saline the depression of the EPSP amplitude was associated with a reduction of the presynaptic spike amplitude at frequencies of > or = 5 Hz. In tetraethylammonium (TEA) saline the width of a TEA-broadened spike was also reduced. The reduction in spike amplitude and spike width correlated with the depression of the EPSP. 5. Certain of these results are consistent with a depletion model of synaptic depression, whereas others are not consistent with this model. The depression may be partly due to an initial depletion of transmitter stores, and partly to modulation of the presynaptic action potential that reduces calcium entry, and therefore transmitter release. The significance of the depression on the motor program for kicking and jumping is discussed.

Animals↗

Development of specific connectivity between premotor neurons and motoneurons in the brain stem and spinal cord.

Astounding progress has been made during the past decade in understanding the general principles governing the development of the nervous system. An area of prime physiological interest that is being elucidated is how the neural circuitry that governs movement is established. The concerted application of molecular biological, anatomical, and electrophysiological techniques to this problem is yielding gratifying insight into how motoneuron, interneuron, and sensory neuron identities are determined, how these different neuron types establish specific axonal projections, and how they recognize and synapse upon each other in patterns that enable the nervous system to exercise precise control over skeletal musculature. This review is an attempt to convey to the physiologist some of the exciting discoveries that have been made, within a context that is intended to link molecular mechanism to behavioral realization. The focus is restricted to the development of monosynaptic connections onto skeletal motoneurons. Principal topics include the inductive mechanisms that pattern the placement and differentiation of motoneurons, Ia sensory afferents, and premotor interneurons; the molecular guidance mechanisms that pattern the projection of premotor axons in the brain stem and spinal cord; and the precision with which initial synaptic connections onto motoneurons are established, with emphasis on the relative roles played by cellular recognition versus electrical activity. It is hoped that this review will provide a guide to understanding both the existing literature and the advances that await this rapidly developing topic.

Afferent Pathways↗

A computer model of neural processes observed in the cat motor cortex during performance of an operant movement.

This report describes a computer model of a "column" in the cat motor cortex. The model includes two layers of two-segment pyramidal neurons with two groups of inhibitory interneurons in each layer, which selectively control the somatic and dendritic segments of the pyramidal cells. In this model, neurons include active sodium, calcium, and several types of potassium currents. Excitatory connections between neurons are of the AMPA and NMDA types, while collateral connections between neurons of the upper layer are mainly of the NMDA type; connections between neurons in the lower layer are of the AMPA type. All inhibitory connections are of the GABA(A) type. The model reproduces the main neuronal processes seen in the cat motor cortex during performance of an operant movement. Pyramidal neurons of the upper layer generate primary and secondary responses to external stimuli. As in real experiments, secondary NMDA-dependent responses appear when GABA(A) inhibition is weakened and disappear when stimulation is increased; these properties of secondary responses are only reproduced when NMDA receptors are located in the terminals of collateral connections. Using only rapid NMDA-independent connections, neurons in the lower layer generate a slow bell-shaped wave of excitation (a "motor command"), which is formed by sequential activation of neurons with dendritic trees of different sizes.

Algorithms↗

The differential regulation of formation of chemical and electrical connections in Helisoma.

Novel chemical and electrical connections form between neurons not normally connected in the buccal ganglia of the snail Helisoma. We examined the cellular and environmental conditions required for the formation of each type of connection. Previous work in situ showed that novel electrical connections could form in response to axotomy. We have now found that axotomy can evoke the formation of novel unidirectional chemical connections between neurons B5 and B4 in addition to a novel electrical connection. The novel chemical connections display all of the normal properties of chemical synapses in Helisoma ganglia. These connections, however, are transient in nature and break 4 days following axotomy. Previous work has shown that conjoint outgrowth is required for the formation of electrical connections. In cell culture we have investigated whether conjoint outgrowth is also required for chemical synaptogenesis. Using neurons B5 and B19 we have found that when neuron pairs make contact in cell culture, under conditions of synchronous neurite extension, both electrical and chemical synapses form. However, if one neuron has ceased extension prior to contact by a growing neuron, electrical synapses never form (Hadley et al., 1983, 1985) but chemical synapses do form. Furthermore, the addition of serotonin (10(-6) M) to culture medium to inhibit neurite extension of B19, but not that of B5, selectively prevents the formation of electrical connections while permitting the formation of chemical synapses. Thus, the timing of contact in relation to the state of neurite extension can specify the type of connection a given neuron can form.

Animals↗