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PubMed1985

[Characteristics of monosynaptic connections between neurons of the callosal system and specific thalamic nuclei].

In the sensorimotor cortex of awake rabbits monosynaptic afferent and efferent connections of callosal neurons (CN) with ipsilateral specific thalamic nuclei (ventral posterolateral, ventral posteromedial, ventral lateral and anteroventral nuclei) were analyzed by electrophysiological method and compared with those of target-units of callosal fibres (TU). It was demonstrated that CN and TU differed in their monosynaptic inputs from the thalamus and in their axons projecting to these structures and/or being a part of the pyramidal tract. These differences were the following: a greater portion of TU had the descending projections (54%) as compared with CN (14%); 22% of TU responded by monosynaptic action potentials to the stimulation of specific thalamic nuclei, while CN never manifested such responses. TU could project to the thalamus through the main axon stem as well as through the collaterals of the pyramidal tract axons. It is supposed that the discovered differences evidence for the much greater convergence of the thalamic relay neuron effect on TU, thus revealing the mechanism underlying the differences both in receptive field properties and in the background and evoked activity of CN and neurons synaptically excited in response to the transcallosal stimulation.

Animals↗
PubMed1998

In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging.

Development of efficient imaging techniques to trace neuronal connections would be very useful. Manganese ion (Mn2+) is an excellent T1 contrast agent for magnetic resonance imaging (MRI). Four reports utilizing radioactive Mn2+ in fish and rat brain indicate that Mn2+ may be useful for tracing neuronal connections. Therefore, the purpose of this work was to determine if Mn2+ can be used as an in vivo MRI neuronal tract tracer. The results indicate that topical administration of MnCI2 solution to the naris of mice as well as to the retinal ganglion cells via intravitreal injection leads to enhancement of contrast along the respective pathways. Therefore, application of Mn2+ to neurons allows the use of MRI to visualize neuronal connections.

Animals↗
PubMedDate not supplied

Evolution of the mechanisms of connection between neurons: electrical, mixed, and chemical synapses.

Investigation of the mechanisms of transmission of stimuli in synapses of isolated perfused spinal cord of cyclostomes, amphibia, reptiles, and mammals demonstrated that the ratio between electrical and chemical synapses decreased progressively in favor of the latter in the transition from primitive toward more highly developed forms. Electrical transmission was not detected in synapses of spinal cords of reptiles and mammals. On the basis of the data, the result of analysis of elementary synaptic processes in synapses uniting electrical and chemical mechanisms of transmission and dendrodendrite electronic interdependences of the motor neurons, a hypothesis is formulated that the number of electrical connections characterizes the union of similar neurons, while in a sequential union of nerve cells of various functions and origins, there are mixed or chemical synapses. The possible cellular mechanisms which are the basis of this phenomenon are discussed.

Afferent Pathways↗
PubMed1993

Synaptic remodelling and elimination as integral processes of synaptogenesis.

It has become increasingly clear that the development and maintenance of synaptic connectivity patterns in the central and peripheral nervous system are not only based on the formation of synapses but include the selective elimination of synaptic subpopulations. Synaptic remodeling and elimination apparently also play a key role in the specification of neuronal connections during ontogenesis of the neocortex in various species. At least three types of synapse elimination have been demonstrated until now, i.e. physiological cell death of synaptically connected neurons, synaptic disconnection and lysosomal degradation, predominantly of presynaptic elements. Occurrence of different elimination types appears to depend on (1) whether the presynaptic or postsynaptic element induces the synaptic reorganization and (2) whether or not the neuron inducing the synapse elimination survives. The same type of synapse elimination may be seen during normal development and under pathological conditions. Factors inducing mental retardation may then either retard synapse formation or interfere with the process of synapse removal. In order to undergo plastic changes in synaptic connections, neurons may respond to exogenous factors such as lack of trophic factors or sensitivity for them (e.g. NGF), long-lasting changes in neuronal activity (e.g. due to drug application or sensory deprivation), hormonal influences (e.g. thyroxin or sexual hormones), learning conditions, or lesions (partial deafferentation and axotomy). The neurons, in turn, may change their responsiveness to exogenous stimuli by inducing synaptic reorganisation.

Age Factors↗
PubMedDate not supplied

[The manifestation of the functional connections between neurons depending on changes in the frequency of their pulsations during the performance by animals of conditioned-reflex food-acquisition reactions].

Multiunit activity in the motor cortex of cats was analysed in the process of food-procuring conditioning to time (interval of 2 min). Functional connections between pairs of neurons each of which changed its current firing frequency during performance of the food-procuring movement were analysed by crosscorrelation method. The same method was implemented for the analysis of functional connections between pairs of neurons which demonstrated no changes in their activity during conditioned movement. Total number of significant correlations in the phase of passive waiting was less between non-reactive neurons than between reactive ones. In the phase of active waiting this difference was eliminated. Relative increase in the number of correlations in the active waiting phase as compared with the passive one was higher in the pairs of non-reactive neurons. This finding is considered as intensification of information analysis and processing in the active phase. Lability of the functional connections was higher in the pairs of reactive neurons which might provide their capability for correction of the functional structure in the case of quick change in a situation or internal state of the animal.

Animals↗
PubMed2002

Exploiting circuit-specific spread of pseudorabies virus in the central nervous system: insights to pathogenesis and circuit tracers.

The neurotropic alpha-herpesviruses are common mammalian pathogens that invade the peripheral and central nervous system of their hosts. Their ability to invade and spread in the nervous system in a directional manner has been exploited to develop them as neuronal circuit tracers. Tracing viruses spread among synaptically connected neurons and, by assaying brain sections for viral antigen or reporter genes expressed from the viruses, chains of synaptically connected neurons can be visualized. Virulent field strains generally are not good tracers, but some attenuated strains perform well. Live attenuated vaccine strains of pseudorabies virus (PRV), such as PRV Bartha, are among the most popular virus circuit tracers. It may be counterintuitive that attenuation results in improved neural tracing that requires extensive replication and spread in the brain. This report summarizes two lines of experiments directed to resolving this apparent paradox and introduces a new paradigm for tracing viruses.

Animals↗
PubMed1982

Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. III. Synaptic connections of electrically coupled pyloric neurons.

1. The pyloric dilator (PD) and anterior burster (AB) neurons in the pyloric system of the lobster stomatogastric ganglion are electrically coupled and synchronously active. We have used the lucifer yellow photoinactivation technique to separate the connections made by the PD motor neurons from those made by the AB interneuron. 2. Photoinactivation of either the two PD neurons or the single AB neuron allowed us to separate the compound inhibitory postsynaptic potentials (IPSPs) in the lateral pyloric (LP) and pyloric (PY) motor neurons resulting from synchronous PD and AB activity into AB-evoked and PD-evoked components. These IPSPs have different time courses, reversal potentials, ion selectivities, and pharmacological properties. 3. Photoinactivation and membrane-potential manipulations indicated that a readily observable IPSP recorded in the AB neuron and correlated with action potentials in the LP neuron is actually an electrotonic potential due to an LP-evoked IPSP in the PD neurons. 4. Selective inactivation of either the two PD neurons or the AB neuron revealed that the IPSP recorded in the ventricular dilator (VD) motor neuron is due solely to AB-released transmitter. 5. The electrical coupling potentials measurable between the AB, PD, and VD neuron somata are due to direct electrical coupling between all of these neurons. 6. Circuit analysis and transmitter identification may be complicated by electrical coupling. We suggest that the presence of electrical coupling between nonidentical neurons may provide a new mechanism that allows changes in synaptic characteristics among neurons within a "hard-wired" circuit.

Animals↗
PubMed2006

BDNF increases synapse density in dendrites of developing tectal neurons in vivo.

Neuronal connections are established through a series of developmental events that involve close communication between pre- and postsynaptic neurons. In the visual system, BDNF modulates the development of neuronal connectivity by influencing presynaptic retinal ganglion cell (RGC) axons. Increasing BDNF levels in the optic tectum of Xenopus tadpoles significantly increases both axon arborization and synapse density per axon terminal within a few hours of treatment. Here, we have further explored the mechanisms by which BDNF shapes synaptic connectivity by imaging tectal neurons, the postsynaptic partners of RGCs. Individual neurons were co-labeled with DsRed2 and a GFP-tagged postsynaptic density protein (PSD95-GFP) to visualize dendritic morphology and postsynaptic specializations simultaneously in vivo. Immunoelectron microscopy confirmed that PSD95-GFP predominantly localized to ultrastructurally identified synapses. Time-lapse confocal microscopy of individual, double-labeled neurons revealed a coincident, activity-dependent mechanism of synaptogenesis and axon and dendritic arbor growth, which is differentially modulated by BDNF. Microinjection of BDNF into the optic tectum significantly increased synapse number in tectal neuron dendritic arbors within 24 hours, without significantly influencing arbor morphology. BDNF function-blocking antibodies had opposite effects. The BDNF-elicited increase in synapse number complements the previously observed increase in presynaptic sites on RGC axons. These results, together with the timescale of the response by tectal neurons, suggest that the effects of BDNF on dendritic synaptic connectivity are secondary to its effects on presynaptic RGCs. Thus, BDNF influences synaptic connectivity in multiple ways: it enhances axon arbor complexity expanding the synaptic territory of the axon, while simultaneously coordinating synapse formation and stabilization with individual postsynaptic cells.

Animals↗
PubMed1990

Sexual differentiation of synaptic connectivity and neuronal plasma membrane in the arcuate nucleus of the rat hypothalamus.

Plasma membranes of the hypothalamic arcuate neurons of the rat show a sexually dimorphic phenotype: the numerical density of intramembrane protein particles is greater in females. Male and female Sprague-Dawley rats, 10, 20 and 100 days old, were studied in order to determine whether sexual differentiation of the neuronal plasma membrane in the soma of arcuate neurons is associated with the establishment of sex differences in the pattern of axo-somatic synaptic contacts. Axo-somatic synapses were counted in thin sections of the arcuate nucleus and intramembrane particles were assessed in freeze-fracture replicas of the neuronal membrane. The number of synapses per length of perikaryal membrane increased from day 10 to day 20 in both sexes, reaching by 20 days values similar to those found on day 100. A sex difference in the number of synapses was observed only in 20-day-old and 100-day-old rats: neurons from females showed a greater number of presynaptic inputs than males (P less than 0.05). This sex difference was abolished by administration of testosterone propionate to 5-day-old females. Quantitative evaluation of freeze-fracture replicas of the arcuate neuronal perikarya revealed sex differences in the numerical density of intramembrane particles at all time points studied: neurons from females contained significantly more particles in their plasma membranes than neurons from males or androgenized females of the same age (P less than 0.001). These results indicate that sexual differentiation of the plasma membrane in neuronal somas precedes the establishment of sex differences in axo-somatic synapses. The results are compatible with a possible role of neuronal membranes in the sexual differentiation of synaptic connectivity.

Animals↗
PubMed1987

Synaptic connections between neurons in living slices of the larval tiger salamander retina.

Synaptic connections between retinal cells were studied by recording simultaneously from pre- and postsynaptic cells in the retinal slice preparation. The time course and waveform of the pre- and postsynaptic light responses were monitored, and the postsynaptic voltage responses to presynaptic current injection were measured. Results obtained provide direct evidence showing that the rod-HBC and rod-HC synapses are sign-preserving, and the rod-DBC, HC-HBC and amacrine-DBC synapses are sign-inverting. Moreover, the synaptic delays between rods and bipolar cells are shorter than that between rods and horizontal cells. The methodology of making retinal slices and the subsequent recording and stimulation procedures are described. The advantages of the retinal slice preparation and its potential in retinal research are discussed.

Ambystoma↗
PubMed1984

Electrical properties and synaptic connections to neurons in parasympathetic colonic ganglia of the cat.

Intracellular recording techniques were used in vitro to analyze the electrophysiological properties and synaptic connections to cat parasympathetic neurons in ganglia located on the serosal surface of the distal colon. Neurons were classified into two types. The first type exhibited spontaneous action potentials at regular and irregular interspike intervals. Spontaneous action potentials were 1) not abolished by superfusion of the ganglia with a modified Krebs solution containing low Ca2+, high Mg2+, or nicotinic ganglionic blocking agents, 2) reduced or abolished by intracellular injection of hyperpolarizing current, and 3) increased by intracellular injection of depolarizing current. We suggest that the generation of spontaneous action potentials may be due to an endogenous depolarizing mechanism and not to cholinergic synaptic input from other neurons located in the ganglia. The second type of neuron termed "quiescent" exhibited a stable transmembrane potential and elicited action potentials in response to electrical stimulation of nerve trunks. Both quiescent and spontaneously discharging neurons receive synaptic input from preganglionic fibers in the pelvic nerve and project their postganglionic axons to colonic nerve fibers that innervate effector structures in the colon.

Action Potentials↗
PubMed1986

The brain as a self-organizing system.

Clinical evidence and numerous results from animal experimentation indicate that cognitive functions have to be learned. Brain structures subserving these functions require sensory experience for their maturation. Genetic instructions are in principle not sufficient to specify neuronal connections with sufficient precision. Self-organization processes are implemented in addition which allow to optimize genetically determined blue prints of connectivity by making use of functional criteria. Thus, neuronal activity becomes an important shaping factor in the development of the structural and functional architecture of the forebrain. To the extent that this neuronal activity is modulated by sensory signals, environmental factors can influence the development of neuronal networks. Recent experiments indicate that these shaping processes are additionally controlled by modulatory systems. Both, the noradrenergic projection from the locus coeruleus and the cholinergic projection from the basal forebrain facilitate activity-dependent long-term changes of neuronal connections during development. The activity of these modulatory systems in turn depends on central states such as arousal, attention, and perhaps also motivation. It is inferred from this evidence that experience-dependent self-organization should not be considered as a passive imprinting process but rather as an active dialogue between the brain and its environment. The hypothesis is discussed that many developmental disturbances which are commonly attributed to deprivation are in fact due to defaults of the CNS which either lead to the formulation of wrong questions or to the reduction of exploratory drive.

Animals↗
PubMedDate not supplied

Long-term changes in the efficiency of excitatory and inhibitory connections in neuronal micronetworks of the motor cortex induced by tetanization of the thalamic nuclei and the sensory cortex.

Tetanization of the ventrolateral nucleus of the thalamus, the red nucleus, and the sensory cortex produced long-term potentiation and depression of the efficiency of both excitatory and inhibitory connections in the neuronal micronetworks of the motor cortex in the cat. Rhythmic stimulation of various structures produced a variety of stable patterns of interneuronal connections in micronetworks. In monosynaptic excitation and disynaptic inhibition, the efficiency of inhibitory transmission was potentiated simultaneously with depression of the efficiency of excitatory transmission in the same post-synaptic cell. The efficiencies of synapses formed by axon collaterals of a given cell on its neighboring cells could change in different directions. These results may indicate that the sign (positive or negative) of modification may be determined by the activity of both cells, i.e., the pre- and post-synaptic cells.

Action Potentials↗
PubMed1990

Viruses as transneuronal tracers.

Tracing chains of neurones requires the use of transneuronal tracers, which are transferred between connected neurones. The conventional transneuronal tracers used so far produce weak labelling of recipient neurones, probably because only a small amount of tracer is transferred. Live neurotropic viruses are beginning to be used as transneuronal tracers. The viruses are replicated in recipient neurones after transneuronal transfer. This replication, which is a unique characteristic of viruses, produces strong transneuronal labelling. The findings indicate that herpes-viruses in particular represent powerful tools for demonstrating neuronal connections across synapses, for example between peripheral nerves and neurones in the brain.

Animals↗
PubMed2006

Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections.

Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in which lmo4 is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditional lmo4 null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Long-term recording on multi-electrode array reveals degraded inhibitory connection in neuronal network development.

Spontaneous neuronal activity plays an important role in development. However, the mechanism that underlies the long-term spontaneous developmental change of cultured neuronal networks in vitro is not well understood. To investigate the contribution of inhibitory and excitatory connections to the development of neuronal networks, dissociated neurons from an embryonic rat hippocampal formation were cultured on a multi-electrode array plate and spontaneous activities were recorded by multi-channel system. These spontaneous activities were compared to bicuculline-induced firings, which were recorded by 60 electrodes simultaneously from 1 to 14 weeks in vitro (WIV). The phenomena showed that the spontaneous firing activities changed from an initial pattern of synchronized bursts to a later pattern of high frequency random spikes. The bicuculline-induced firing activities transformed from a pattern of synchronized bursts throughout all active sites in 3 WIV, to a pattern of local synchronized or random spikes appearing in the intervals of synchronized bursts after 11 WIV, while the firing rate hardly changed. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, blocked all activities while CNQX inhibited only the local synchronized or random spikes. These suggest that the inhibitory connection was age-dependent degraded in vitro and the developmental spontaneous firing pattern was built by the homeostatic balance of the excitatory-inhibitory connection networks. Long-term cultures on MEA provided a useful tool to measure the relationship between spontaneous developmental change and pharmacological influence in vitro.

Animals↗
PubMed1991

Cat pontine omnipause neurons: direct inhibitory connection with Forel's field burst neurons participating in the genesis of vertical saccades.

This study investigates synaptic connections of omnipause neurons (OPNs) in the midline pontine tegmentum with vertical medium-lead burst neurons (BNs) in the Forel's field H (FFH), using the microstimulation and spike-triggered averaging techniques in chronically prepared alert cats. OPNs on both sides were antidromically activated by microstimulation at the recording sites of the BNs. Systematic tracking with the stimulating microelectrode revealed indications of profuse axonal branching of OPNs within the BN area. Antidromic spikes of the BNs evoked from the oculomotor nucleus and spike bursts of the BNs associated with saccades were suppressed by OPN area microstimulation. Averaged field potentials in the BN area triggered by spikes of OPNs showed monosynaptic positive waves. These results all but confirm the existence of direct inhibitory synaptic connections of OPNs with the BNs in the FFH. The role of OPNs in the genesis of vertical saccades was also discussed.

Animals↗
PubMed2001

Solving the binding problem of the brain with bi-directional functional connectivity.

We propose a neural network model which gives one solution to the binding problem on the basis of 'functional connectivity' and bidirectional connections. Here, 'functional connectivity' is dynamic neuronal connectivity peculiar to temporal spike coding neural networks with coincidence detector neurons. The model consists of a single primary map and two higher modules which extract two different features shown on the primary map. There exist three layers in each higher module and the layers are connected bi-directionally. An object in the outer world is represented by a 'global dynamical cell assembly' which is organized across the primary map and the two higher modules. Detailed, but spatially localized, information is coded in the primary map, whereas coarse, but spatially extracted information or globally integrated information is coded in the higher modules. Computer simulations of the proposed model show that multiple cell assemblies sharing the same neurons partially can co-exist. Furthermore, we introduce a three-dimensional J-PSTH (Joint-Peri Stimulus Time Histogram) which is capable of tracking such cell assemblies, altering its constituent neurons as in our proposed model.

Action Potentials↗