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PubMed2003

Transient activation in a network of coupled map neurons.

The focus of this Letter is on the activity of a network of neurons pairwise coupled by inhibitory connections. Each neuron is represented by a two-dimensional map capable, when isolated, of a rich variety of complex dynamical regimes. It is shown that the network exhibits a stimulus-dependent sequential activation and inactivation of subgroups of neurons. This complex behavior is rather similar to some spatiotemporal features observed in the first stages of the olfaction process in some insects and suggests the possibility of large scale simulation of these processes by using reasonable computational capabilities.

Action Potentials↗
PubMed1992

Simultaneous characterization of efferent and afferent connectivity, neuroactive substances, and morphology of neurons.

We present a method for establishing in a single experiment four characteristics of individual neurons: the efferent and afferent connectivity, the morphology, and the content of a particular neuroactive substance. The connectivity of the neurons is determined by retrograde fluorescent tracing with Fast Blue and anterograde tracing with the lectin Phaseolus vulgaris leucoagglutinin (PHA-L). After fixation, the brain is cut into 300-micron thick slices. Neurons containing retrogradely transported Fast Blue are intracellularly injected with the fluorescent dye Lucifer Yellow to fill their dendritic trees. The slices are then resectioned at 20-40 microns. One section through the soma of a Lucifer Yellow-filled neuron is selected for the detection of a neuroactive substance contained by this cell [immunofluorescence, secondary antiserum conjugated to tetramethylrhodamine (TRITC)]. Using appropriate filtering, it can be determined in the fluorescence microscope whether a Lucifer Yellow-containing cell body has also been labeled with TRITC, i.e., whether it is immunoreactive for this neuroactive substance. The adjacent sections are subjected to dual peroxidase immunocytochemistry with different chromogens to visualize the PHA-L-labeled afferent fibers (nickel-enhanced diaminobenzidine, blue-black reaction product) and to stabilize the Lucifer Yellow (diaminobenzidine, brown reaction product) in the dendrites of the intracellular injected cells. The other sections are used for electron microscopic visualization of the transported PHA-L. The relationships between the PHA-L-labeled afferent fibers (blue color) and the dendrites of the intracellularly Lucifer Yellow-injected, retrogradely Fast Blue-labeled cells (brown color) are studied by light microscopy. The electron microscope supplies ultrastructural data on the PHA-L-labeled axon terminals.

Afferent Pathways↗
PubMed2000

Secondary nicotinic synapses on sympathetic B neurons and their putative role in ganglionic amplification of activity.

The strength and number of nicotinic synapses that converge on secretomotor B neurons were assessed in the bullfrog by recording intracellularly from isolated preparations of paravertebral sympathetic ganglia 9 and 10. One input to every B neuron invariably produced a suprathreshold EPSP and was defined as the primary nicotinic synapse. In addition, 93% of the cells received one to four subthreshold inputs that were defined as secondary nicotinic synapses. This contradicts the prevailing view, which has long held that amphibian B neurons are singly innervated. More important, the results revealed that B cells provide the simplest possible experimental system for examining the role of secondary nicotinic synapses on sympathetic neurons. Combining the convergence data with previous estimates of divergence indicates that the average preganglionic B neuron forms connections with 50 ganglionic B neurons and that the majority of these nicotinic synapses are secondary in strength. Secondary EPSPs evoked by low-frequency stimulation ranged from 0.5 to 10 mV in amplitude and had an average quantal content of 1. Nonetheless, secondary synapses could trigger action potentials via four mechanisms: spontaneous fluctuations of EPSP amplitude, two-pulse facilitation, coactivation with other secondary synapses, and coactivation with a slow peptidergic EPSP. The data were used to formulate a stochastic theory of integration, which predicts that ganglia function as amplifiers of the sympathetic outflow. In this two-component scheme, primary nicotinic synapses mediate invariant synaptic gain, and secondary nicotinic synapses mediate activity-dependent synaptic gain. The model also provides a common framework for considering how facilitation, metabotropic mechanisms, and preganglionic oscillators regulate synaptic amplification in sympathetic ganglia.

Animals↗
PubMed1995

Regeneration of neuromuscular connections in crayfish allotransplanted neurons.

Transplantation of whole ganglia was used to study the regeneration of four of the neurons that innervate the superficial flexor muscles of the crayfish Procambarus clarkii. The isolated ganglia containing the somas of these neurons were successfully transplanted from one crayfish to another. Reinnervation proceeded across the muscle surface and by 8 to 10 weeks connections were detected across the entire target field. At different time periods after the transplant, junction potentials (JPs) produced in phase with spontaneous neuronal spikes were recorded. The distribution of JP sizes and their decay times were examined. JPs from transplanted preparations were smaller than JPs from control or normal regeneration animals. These JPs also failed to facilitate when stimulated at 1 and 10 Hz. These are normal characteristics of immature terminals, but in the transplant preparations, once established, they remained stable for the duration of the study. Thus, synaptogenesis appears to be arrested at a stage before synaptic efficacy is established in the allotransplants. In addition, connectivity maps were plotted for each axon over the muscle surface. Some muscle fibers did not receive any contacts, and overall innervation leveled off at around 60% of the muscle fibers, remaining stable for the duration of this study. Despite the incomplete physiological innervation, however, three of the four neurons showed the same medial/lateral preferences observed in control animals, regenerating their original patterns of connectivity across the muscle surface.

Animals↗
PubMed1997

Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function.

Free recall and recognition are simulated in a network model of the hippocampal formation, incorporating simplified simulations of neurons, synaptic connections, and the effects of acetylcholine. Simulations focus on modeling the effects of the acetylcholine receptor blocker scopolamine on human memory. Systemic administration of scopolamine is modeled by blockade of the cellular effects of acetylcholine in the model, resulting in memory impairments replicating data from studies on human subjects. This blockade of cholinergic effects impairs the encoding of new input patterns (as measured by delayed free recall), but does not impair the delayed free recall of input patterns learned before the blockade. The impairment is selective to the free recall but not the recognition of items encoded under the influence of scopolamine. In the model, scopolamine blocks strengthening of recurrent connections in region CA3 to form attractor states for new items (encoding impaired) but allows recurrent excitation to drive the network into previously stored attractor states (retrieval spared). Neuron populations representing items (individual words) have weaker recurrent connections than neuron populations representing experimental context. When scopolamine further weakens the strength of recurrent connections it selectively prevents the subsequent reactivation of item attractor states by context input (impaired free recall) without impairing the subsequent reactivation of context attractor states by item input (spared recognition). This asymmetry in the strength of attractor states also allows simulation of the list-strength effect for free recall but not recognition. Simulation of a paired associate learning paradigm predicts that scopolamine should greatly enhance proactive interference due to retrieval of previously encoded associations during storage of new associations.

Cholinergic Antagonists↗
PubMed2003

Resonant synchronization in heterogeneous networks of inhibitory neurons.

Brain rhythms arise through the synchronization of neurons and their entrainment in a regular firing pattern. In this process, networks of reciprocally connected inhibitory neurons are often involved, but what mechanism determines the oscillation frequency is not completely understood. Analytical studies predict that the emerging frequency band is primarily constrained by the decay rate of the unitary IPSC. We observed a new phenomenon of resonant synchronization in computer-simulated networks of inhibitory neurons in which the synaptic current has a delayed onset, reflecting finite spike propagation and synaptic transmission times. At the resonant level of network excitation, all neurons fire synchronously and rhythmically with a period approximately four times the mean delay of the onset of the inhibitory synaptic current. The amplitude and decay time constant of the synaptic current have relatively minor effects on the emerging frequency band. By varying the axonal delay of the inhibitory connections, networks with a realistic synaptic kinetics can be tuned to frequencies from 40 to >200 Hz. This resonance phenomenon arises in heterogeneous networks with, on average, as few as five connections per neuron. We conclude that the delay of the synaptic current is the primary parameter controlling the oscillation frequency of inhibitory networks and propose that delay-induced synchronization is a mechanism for fast brain rhythms that depend on intact inhibitory synaptic transmission.

Action Potentials↗
PubMed2003

Organization of neural networks in the neocortex.

Implanted semimicroelectrodes were used in conscious cats to record spike discharges from groups of close-lying neurons, i.e., multineuron activity, in the deep layers of the frontal and motor areas of the cortex at different levels of food motivation. Spike activity was extracted from 4-7 neurons and interneuronal interactions were studied by cross-correlation analysis between neighboring neurons in each zone (local networks) and between neurons in two zones (distributed networks) with analysis epochs of 0-100 msec. The results showed that neurons in local networks can be divided into two subgroups: neurons with high-amplitude spikes and a predominance of output (divergent) connections and neurons with low-amplitude spikes and a predominance of input (convergent) connections. Local networks are based on powerful monosynaptic connections (with delays of up to 2 msec) between large and small neurons. Most connections in distributed networks were between small neurons in local networks of the frontal cortex and large neurons in local networks in the motor cortex. Food deprivation for 24 h mainly affected late (with delays of 2-100 msec) cross-correlation interneuronal relationships in both local and distributed networks.

Animals↗
PubMed1985

Regeneration of axons and synaptic connections by touch sensory neurons in the leech central nervous system.

In studies of axonal regeneration, it has been difficult to determine (a) whether growth along the normal pathway is important for restoration of connections with previous targets and (b) whether the new synapses resemble the old in strength and location. To address these problems at the level of individual nerve cells, we have studied touch (T) sensory neurons in the leech after their axons have been severed and we have confirmed that their axons regenerate electrical connections with some of their usual synaptic targets in the central nervous system. Injections of horseradish peroxidase and Lucifer Yellow dye into separate T cells in unoperated animals showed that T cell axons typically run close to one another within single ganglia or from ganglion to ganglion. Knowledge of one T cell's arborizations thus revealed the groundplan of others in the same ganglia and the sites of apparent contact with its synaptic targets. For regenerating axons, those sprouts that encountered the normal pathway (as marked by homologous axons) grew preferentially along it. Despite the striking coincidence of old and new pathways, regenerated branching patterns within the ganglionic neuropils were usually incomplete and sometimes had atypical branches. Synaptic connections with normal targets (other T cells as well as S and C cells) were abnormally weak physiologically. The numbers of apparent contacts seen with the light microscope were also lower than normal. In addition, the strength of the synaptic potentials, normalized to the number of contacts (calculated as microvolts per contact), was generally smaller in the regenerated connections than in the controls, and smallest at earliest times, during the first 6 weeks following injury. It thus appears to be characteristic of T cell regeneration that axon regrowth is aided by the recognition of specific pathways and that successful regeneration, as assayed anatomically and physiologically, occurs frequently but usually incompletely.

Animals↗
PubMedDate not supplied

Neural population structures and consequences for neural coding.

Researchers studying neural coding have speculated that populations of neurons would more effectively represent the stimulus if the neurons "cooperated:" by interacting through lateral connections, the neurons would process and represent information better than if they functioned independently. We apply our new theory of information processing to determine the fidelity limits of simple population structures to encode stimulus features. We focus on noncooperative populations, which have no lateral connections. We show that they always exhibit positively correlated responses and that as population size increases, they perfectly represent the information conveyed by their inputs regardless of the individual neuron's coding scheme. Cooperative populations, which do have lateral connections, can, depending on the nature of the connections, perform better or worse than their noncooperative counterparts. We further show that common notions of synergy fail to capture the level of cooperation and to reflect the information processing properties of populations.

Algorithms↗
PubMed1986

Arrangement and connections of mesencephalic trigeminal neurons in the rat.

The morphology of the mesencephalic trigeminal nucleus was examined microscopically in serial frozen sections. The nucleus extends over a length of about 4.5 mm, and its cell number was calculated to range from 1,000 to 1,600. 60% of the cells were located in the caudal third of the nucleus. Clustering of large unipolar cells was seen throughout the nucleus. Small spindle-shaped multipolar cells were found in the pontine part of the nucleus. The efferent connections of the mesencephalic trigeminal neurons were investigated by means of iontophoretically delivered Phaseolus vulgaris leuco-agglutinin or horseradish peroxidase after electrophysiological identification of mesencephalic trigeminal neurons. All projections were found ipsilateral to the injection site; they were confined to the trigeminal motor nucleus, especially to its lateral part, and to the dorsolateral reticular formation. The latter projection area included the supratrigeminal nucleus, the nucleus of Probst, and the parvocellular reticular zone. There were no direct projections to the facial or hypoglossal motor nuclei. It is concluded that proprioceptive input from one side is mediated polysynaptically to the bilateral oral final common-path neurons, with the exception of the ipsilateral trigeminal motoneurons.

Animals↗
PubMed1992

NeuronC: a computational language for investigating functional architecture of neural circuits.

A computational language was developed to simulate neural circuits. A model of a neural circuit with up to 50,000 compartments is constructed from predefined parts of neurons, called "neural elements". A 2-dimensional (2-D) light stimulus and a photoreceptor model allow simulating a visual physiology experiment. Circuit function is computed by integrating difference equations according to standard methods. Large-scale structure in the neural circuit, such as whole neurons, their synaptic connections, and arrays of neurons, are constructed with procedural rules. The language was evaluated with a simulation of the receptive field of a single cone in cat retina, which required a model of cone-horizontal cell network on the order of 1000 neurons. The model was calibrated by adjusting biophysical parameters to match known physiological data. Eliminating specific synaptic connections from the circuit suggested the influence of individual neuron types on the receptive field of a single cone. An advantage of using neural elements in such a model is to simplify the description of a neuron's structure. An advantage of using procedural rules to define connections between neurons is to simplify the network definition.

Computer Simulation↗
PubMed1998

Tetanus toxin-enhanced GABA immunoreactivity in living neurons.

Analysis of the connectivity between different neuronal cell types is dependent on an appreciation of their dendritic and axonal arborizations. A detailed study of the dendrites and axons of GABAergic neurons has been thwarted by the lack of a suitable technique for enhancing GABA immunoreactivity. This article describes a procedure using tetanus toxin which, when applied to organotypic hippocampal cultures, considerably enhances the immunoreactivity in the dendrites and axons of the GABA- and somatostatin-containing neurons and clearly demonstrates the co-localization of GABA and somatostatin immunoreactivities in the same neuron. Tetanus toxin was applied to the culture medium on Day 14 for a 24-hr period and the cultures were fixed at the end of Day 18. Tetanus toxin-treated cultures (n = 30) or untreated cultures (n = 40) were incubated for either GABA or somatostatin immunoreactivity. Tetanus toxin-treated cultures used for co-localization studies (n = 20) were incubated for both GABA and somatostatin immunoreactivity.

Animals↗
PubMed1986

Scanning electron microscopic studies of bullfrog sympathetic neurons exposed by enzymatic removal of connective tissue elements and satellite cells.

The ninth and tenth abdominal sympathetic ganglia of bullfrogs were studied by light microscopy and transmission and scanning electron microscopy after the removal of the connective tissue elements overlying the neurons. Digestion of tissues with trypsin and subsequent acid hydrolysis exposed the unipolar neurons, which remained covered by their satellite cells. The preganglionic innervation was visible on the proximal segment and axon hillock region of the postganglionic neurite. Clusters of small cells seen at the periphery of ganglia probably corresponded to groups of cells with abundant catecholamine-containing granules (SIF cells). Digestion with collagenase and protease removed some or all of the satellite cells in addition to the connective tissue. The true neuronal surfaces had short finger-like processes, whereas the external surfaces of satellite cells were smooth. Preganglionic nerve varicosities were clearly visible on the proximal segment of the postganglionic neurite, on the axon hillock and on the cell body of neurons. A few axonal varicosities were fractured to reveal the synaptic vesicles within. The possible effects of the distribution and glial ensheathment of nerve varicosities on their function are discussed.

Animals↗
PubMed1999

Direct connection of the nucleus reticularis gigantocellularis neurons with neck motoneurons in cats.

Functional connections of single reticulospinal neurons (RSNs) in the nucleus reticularis gigantocellularis (NRG) with ipsilateral dorsal neck motoneurons were examined with the spike-triggered averaging technique. Extracellular spikes of single NRG-RSNs activated antidromically from the C6, but not from the L1 segment (C-RSNs) were used as the trigger. These neurons were monosynaptically activated from the superior colliculus and the cerebral peduncle. Single-RSN PSPs were recorded in 43 dorsal neck motoneurons [biventer cervicis and complexus (BCC) and splenius (SPL)] for 21 NRG-RSNs and 135 motoneurons tested. All synaptic potentials were EPSPs, and most of their latencies, measured from the triggering spikes, were 0.8-1.5 ms, which is in a monosynaptic range. The amplitudes of single-RSN EPSPs were 10-360 microV. Spike-triggered averaging revealed single-RSN EPSPs in multiple motoneurons of the same species (SPL or BCC), their locations extending up to nearly 1 mm rostrocaudally. Synaptic connections of single RSNs with both SPL and BCC motoneurons were also found with some predominance for one of them. The results provide direct evidence that NRG-RSNs make monosynaptic excitatory connections with SPL and BCC motoneurons. It appears that some NRG-RSNs connect predominantly with SPL motoneurons and others with BCC motoneurons.

Animals↗
PubMed2005

Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice.

The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic method to map upstream neuronal populations that have synaptic connections to orexin neurons and revealed that orexin neurons receive input from several brain areas. These include the amygdala, basal forebrain cholinergic neurons, GABAergic neurons in the preoptic area, and serotonergic neurons in the median/paramedian raphe nuclei. Monoamine-containing groups that are innervated by orexin neurons do not receive reciprocal connections, while cholinergic neurons in the basal forebrain have reciprocal connections, which might be important for consolidating wakefulness. Electrophysiological study showed that carbachol excites almost one-third of orexin neurons and inhibits a small population of orexin neurons. These neuroanatomical findings provide important insights into the neural pathways that regulate sleep/wakefulness states.

Animals↗
PubMed1988

Voltage-dependent currents prolong single-axon postsynaptic potentials in layer III pyramidal neurons in rat neocortical slices.

1. Using isolated slices of rat cingulate and sensorimotor cortex, intracellular recordings were obtained from pyramidal neurons in layer III. Simultaneous extracellular recordings were obtained from neurons in ventral layer III and layer IV. Spike-triggered averaging was employed to investigate synaptic connections from neurons in layers III/IV to pyramidal cells in layer III. 2. Of 701 simultaneously recorded pairs of neurons, comprising 699 extracellularly and 128 intracellularly recorded neurons, synaptic connections were demonstrated in 30 pairs. Of these, 29 were excitatory postsynaptic potentials (EPSPs) and 1, an inhibitory postsynaptic potential (IPSP). Single-axon EPSPs with a wide variety of amplitudes were recorded: the range recorded at membrane potentials between -68 and -72 mV was 0.079-2.3 mV. Comparing recordings obtained from different cells, EPSP amplitude was found to be independent of both the membrane resistance of the postsynaptic neuron and the EPSP time course; i.e., the largest EPSPs were not necessarily those recorded from neurons with the highest input resistance, nor those with the briefest time course. 3. Shape indices: width at half amplitude and rise-time, indicative of both proximal and distal synaptic locations were obtained. Normalized rise-times were between 0.1 and 2 times the membrane time constant and half-widths between 0.8 and 20 times. 4. The majority of postsynaptic neurons displayed nonlinear voltage relations typical of pyramidal neurons, and the contribution to EPSP shape of voltage-dependent currents was investigated. EPSP amplitude and duration were found to be dependent on membrane potential. The majority of single-axon EPSPs (26 of 29), increased in amplitude and duration with membrane depolarization over the range -95 - -50 mV, despite the significant decrease in driving force for the EPSP that would be expected to accompany such large depolarizations. This increase coincided with an increase in the amplitude of voltage responses to small injected current pulses. 5. It is concluded that the amplitude and time course of single-axon EPSPs recorded in cortical pyramidal somata are affected not only by the amplitude of the postsynaptic current and the location(s) of the synapse(s) relative to the soma, but also by voltage-dependent currents. The possibility that the increase in amplitude and duration of these EPSPs with membrane depolarization is due to N-methyl-D-aspartate receptor involvement is discussed.

Animals↗
PubMedDate not supplied

[Comparative study of interneuronal relations in neighboring microareas of the cerebral cortex in untrained wakeful cats].

Multineuronal activity was studied in unrestrained cats with bundles of 7 electrodes (50 mcm dia of the tips) chronically implanted in the auditory and motor cortex. Impulses of the highest and lowest amplitude were isolated from each neurogram by an amplitude discriminator. By means of AI-128 analyser interval cross-histograms were built for spike series, isolated from two simultaneous records. Functional connections between neurones located under different electrodes at a distance of up to 500 mcm were defined by statistical dependence of spike series. A higher level of interneuronal interaction was revealed in the motor cortex. In both cortical zones, excitatory connections dominated for neurones which generated high amplitude spikes. For neurones with low amplitude spikes, connections of the inhibitory type were typical in the auditory cortex, and inhibitory and inhibitory-excitatory connections were typical for neurones in the motor cortex. The excitatory type of dependence in the auditory cortex was manifested on histograms during the first 6 ms after the triggering spike, in the motor cortex-by 4 to 6 ms more frequently; the inhibitory type was manifested in both zones only during the first 2 ms.

Animals↗