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Involvement of pedal neurons in cardio-renal regulation and their connections with identified visceral cells in Helix pomatia L.

Involvement of the cells of pedal ganglia in the regulation of heart activity and their connections with visceral neurons was studied in the central nervous system of Helix pomatia L. It was found that (1) numerous cells of pedal ganglia receive inputs from the heart. The reaction of the pedal cells to heart afferents was characteristic: initial high frequency increase of firing followed by inhibition, then a secondary tonic increase occurred in activity. Some of the pedal cells were activated after a brief delay; (2) many of the cells of the visceral and right parietal ganglia were activated simultaneously with pedal neurons during tactile stimulation of the heart. In different ganglia the answer to heart afferents can be observed to the same or opposite directions but its duration was identical in every cell; (3) one cell of the left pedal ganglion (LP3) formed monosynaptic connections with several cells of the visceral ganglion. The axons of the visceral cells, connected monosynaptically to the neurons LP3, runs into the intestinal nerve. LP3 caused EPSPs on the visceral cells; (4) the heart excitatory motoneuron V41, simultaneously with a number of pedal cells, receives excitatory inputs from the heart. The heart excitatory motoneuron is involved in the afferent and efferent pathways of heart regulatory network; (5) a motoneuron (V43) was identified to cause relaxation of the heart, giving branches into the intestinal nerve and similarly to other motoneurons activated by heart afferents.

Action Potentials↗

Direct synaptic connections of axons from superior colliculus with identified thalamo-amygdaloid projection neurons in the rat: possible substrates of a subcortical visual pathway to the amygdala.

The aim of the present study was to identify synaptic contacts from axons originating in the superior colliculus with thalamic neurons projecting to the lateral nucleus of the amygdala. Axons from the superior colliculus were traced with the anterograde tracers Phaseolus vulgaris leucoagglutinin or the biotinylated and fluorescent dextran amine "Miniruby." Thalamo-amygdaloid projection neurons were identified with the retrograde tracer Fluoro-Gold. Injections of Fluoro-Gold into the lateral nucleus of the amygdala labeled neurons in nuclei of the posterior thalamus which surround the medial geniculate body, viz. the suprageniculate nucleus, the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the peripeduncular nucleus. Anterogradely labeled axons from the superior colliculus terminated in the same regions of the thalamus. Tecto-thalamic axons originating from superficial collicular layers were found predominantly in the suprageniculate nucleus, whereas axons from deep collicular layers were detected in equal density in all thalamic nuclei surrounding the medial geniculate body. Double-labeling experiments revealed an overlap of projection areas in the above-mentioned thalamic nuclei. Electron microscopy of areas of overlap confirmed synaptic contacts of anterogradely labeled presynaptic profiles originating in the superficial layers of the superior colliculus with retrogradely labeled postsynaptic profiles of thalamo-amygdaloid projection neurons. These connections may represent a subcortical pathway for visual information transfer to the amygdala.

Amygdala↗

Synaptic efficacy and reliability of excitatory connections between the principal neurones of the input (layer 4) and output layer (layer 5) of the neocortex.

A prerequisite for the understanding of how a cortical column functions is a description of small and defined neuronal circuits consisting of only a few identified neurones. Here we summarise, with particular reference to the barrel cortex, the morphological and physiological properties of two synaptic connections, namely those between pairs of spiny neurones in layer 4 and pairs of pyramidal cells in layer 5. While layer 4 spiny neurones are the cortical input neurones that amplify and relay incoming excitation from the periphery, layer 5 pyramidal cells integrate neuronal activity both within and across cortical columns and subsequently distribute it to both cortical and subcortical brain regions.

Animals↗

Redirected perforant and commissural of connections of eutopic and ectopic neurons in the hippocampus of methylazoxymethanol-acetate treated rats.

In an earlier study, it was reported that clusters of ectopic neurons developed postnatally in the hippocampus of rats which were exposed to Methylazoxymethanol acetate (MAMac) during fetal development (Singh, 1977b). This paper describes the perforant tract and commissural connections of hippocampal eutopic and ectopic neurons. These connections were traced with a reduced-silver method (Eager, 1970). Two observations of significance were made: (i) Ectopic neurons misplaced in stratum radiatum received terminals from axons in the perforant tract. The upper boundary for these redirected fibers was stratum pyramidale--approximately 350 mu outside the normal boundary which is situated near the hippocampal fissure. (ii) Ectopic neurons received a dramatically reduced commissural projection, compared with eutopic pyramidal neurons in Ammon's horn. Eutopic neurons in the hippocampus were found to receive afferent perforant tract and commissural fibers in the same way--i.e., density and distribution, as in control rats.

Animals↗

Enhanced synaptic transmission at identified synaptic connections in the cerebral ganglion of Aplysia.

The identified A-B neuron synaptic connections in the cerebral ganglion of Aplysia exhibited a novel form of enhanced synaptic transmission. A brief high-frequency train of action potentials (2 s, 10-30 Hz) in the presynaptic A neurons produced a long-lasting increase in the amplitude of excitatory postsynaptic potentials (EPSPs) in B neurons. The increase in synaptic efficacy was termed slow developing potentiation (SDP) since the EPSP amplitude increased slowly with the peak occurring 5 min after the tetanizing train. Peak EPSP amplitudes increased relative to the initial EPSP by an average of greater than 250%. SDP decayed as a single exponential with a time constant of tau = 24 min. The enhanced transmission was neuron specific. Only the connections made by the tetanized A neuron were potentiated. However, potentiation apparently occurred at all the synapses made by the tetanized A neuron. Tetanizing the postsynaptic B neurons neither induced, nor when paired with A neuron tetanization, increased SDP. SDP appears to be primarily due to increased transmitter release by the presynaptic neuron.

Action Potentials↗

Circuitry of rat barrel cortex investigated by infrared-guided laser stimulation.

Infrared-guided laser stimulation was used to examine the synaptic connectivity of neurons in rat barrel cortex. Layer V pyramidal neurons were visualized by infrared videomicroscopy and their membrane potential was recorded with patch pipettes. Presumptive presynaptic neurons were activated by uncaging glutamate with the light of a uv laser directed onto these neurons superfused with medium containing caged glutamate. Synaptic connections were identified by postsynaptic potentials following laser stimulation. The most frequent synaptic connections were found between layer V pyramidal neurons. The probability of this intralaminar input declined monotonically with the lateral distance between stimulated and recorded neuron. In contrast, input from layer II/III onto lamina V neurons showed a periodic organization. Synaptic connections originating from this lamina clearly reflected the barrel structure, with more input originating from the barrel column side, and less input from the barrel column centre. Thus, a barrel-specific organization seems to be especially pronounced for synaptic input from layer II/III to neurons of layer V.

Animals↗

Specification of synaptic connections between sensory and motor neurons in the developing spinal cord.

Experimental studies of mechanisms underlying the specification of synaptic connections in the monosynaptic stretch reflex of frogs and chicks are described. Sensory neurons innervating the triceps brachii muscles of bullfrogs are born throughout the period of sensory neurogenesis and do not appear to be related clonally. Instead, the peripheral targets of these sensory neurons play a major role in determining their central connections with motoneurons. Developing thoracic sensory neurons made to project to novel targets in the forelimb project into the brachial spinal cord, which they normally never do. Moreover, these foreign sensory neurons make monosynaptic excitatory connections with the now functionally appropriate brachial motoneurons. Normal patterns of neuronal activity are not necessary for the formation of specific central connections. Neuromuscular blockade of developing chick embryos with curare during the period of synaptogenesis still results in the formation of correct sensory-motor connections. Competitive interactions among the afferent fibers also do not seem to be important in this process. When the number of sensory neurons projecting to the forelimb is drastically reduced during development, each afferent still makes central connections of the same strength and specificity as normal. These results are discussed with reference to the development of retinal ganglion cells and their projections to the brain. Although many aspects of the two systems are similar, patterned neural activity appears to play a much more important role in the development of the visual pathway than in the spinal reflex pathway described here.

Animals↗

APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin-alpha connection.

Protein ubiquitination has critical roles in neuronal physiology and defects in protein ubiquitination have been implicated in neurodegenerative pathology. The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle transitions in proliferating cells by acting on cyclins and components of the mitotic/meiotic apparatus. Documentation of APC/C's action beyond cell division is sparse. In the past year, however, novel and surprising roles for APC/C in postmitotic neurons, particularly in the modulation of axonal growth and synaptic functions, have been revealed. APC/C and its activator Cdh-1 are found in good abundance in neurons, and these seem to function at different cellular locations, modulating apparently diverse processes such as axonal growth and synaptic function. Interestingly, there also appears to be a single link to these apparently divergent actions of APC/C in neurons--the multi-domain, multi-functional scaffolding protein Liprin-alpha which is an APC/C substrate.

Anaphase-Promoting Complex-Cyclosome↗

[Plastic changes of the network properties of neurons during learning in the cat].

Functional connections between neurones of various types in microareas and between microareas of the motor cortex in cats have been studied during elaboration of an electro-defensive reflex to sound. A difference has been shown between neighbouring neurones in formation of their contacts with nearby neurones located within an area of 500 mc. Neurones generating spikes of high amplitude had more active "outputs" to neurones situated at different distances, while neurones generating spikes of low amplitude had more active "inputs" to them. On the other hand, as a result of conditioning "inputs" to distant neurones underwent more significant changes in the first type of neurones, and in the second type--the "outputs" changed more markedly.

Animals↗

Monosynaptic connections between serotonin-containing neurones labelled by 5,6-dihydroxytryptamine-induced pigmentation in the snail Helix pomatia L.

Microelectrophysiological experiments were carried out on in vivo 5,6-dihydroxytryptamine-induced pigment-labelled serotonin-containing neurones of Helix pomatia. Excitatory chemical monosynaptic connections were found between the giant pedal LP3 neurone and several follower cells in the visceral and right parietal ganglia. These neurones have previously been described to be involved in regulation of visceral functions. Monitoring changes in identified monosynaptic connections between pairs of serotonin-containing neurones aids the cellular analysis of behavioural plasticity.

5,6-Dihydroxytryptamine↗

Trigeminal nociceptive neurons in the subnucleus reticularis ventralis. I. Response properties and afferent connections.

Trigeminal nociceptive neurons within the subnucleus reticularis ventralis medullae oblongatae (SRV), which lies ventral to the trigeminal subnucleus caudalis and subnucleus reticularis dorsalis medullae oblongatae, were studied in urethane/chloralose-anesthetized cats and monkeys. These neurons were called 'SRV neurons'. They were almost regularly excited by pressure to the ipsilateral cornea or to both corneas at a strength well above the human corneal pain threshold. Most of them were activated by noxious mechanical stimulation of the pinna, face and/or tongue. A significant fraction of SRV units was responsive to tapping of the ipsilateral dorsum of the nose and/or electrical stimulation of tooth pulp afferents. Evidence was obtained that responses to tapping of the dorsum of the nose were due to mechanical distortion of the nasal mucosa. Intracellular injection of HRP into SRV neurons demonstrated that injected neurons were large neurons characteristic of the SRV. Trigeminal tractotomy just rostral to the obex did not eliminate responses of SRV units to trigeminal inputs. Neurons relaying trigeminal inputs to SRV neurons were electrophysiologically identified in the nucleus reticularis parvocellularis which is ventromedially adjacent to the subnuclei oralis and interpolaris of the trigeminal spinal tract nucleus. These findings were supported by HRP injection into the SRV. Units having receptive fields similar to those of SRV neurons were found in lamina VII of the first cervical cord, suggesting that SRV neurons may be trigeminal lamina VII neurons.

Afferent Pathways↗

Reward-predicting activity of dopamine and caudate neurons--a possible mechanism of motivational control of saccadic eye movement.

Recent studies have suggested that the basal ganglia are related to motivational control of behavior. To study how motivational signals modulate motor signals in the basal ganglia, we examined activity of midbrain dopamine (DA) neurons and caudate (CD) projection neurons while monkeys were performing a one-direction-rewarded version (1DR) of memory-guided saccade task. The cue stimulus indicated the goal position for an upcoming saccade and the presence or absence of reward after the trial. Among four monkeys we studied, three were sensitive to reward such that saccade velocity was significantly higher in the rewarded trials than in the nonrewarded trials; one monkey was insensitive to reward. In the reward-sensitive monkeys, both DA and CD neurons responded differentially to reward-indicating and no-reward-indicating cues. Thus DA neurons responded with excitation to a reward-indicating cue and with inhibition to a no-reward-indicating cue. A group of CD neurons responded to the cue in their response fields (mostly contralateral) and the cue response was usually enhanced when it indicated reward. In the reward-insensitive monkey, DA neurons showed no response to the cue, while the cue responses of CD neurons were not modulated by reward. Many CD neurons in the reward-sensitive monkeys, but not the reward-insensitive monkey, showed precue activity. These results suggest that DA neurons, with their connection to CD neurons, modulate the spatially selective signals in CD neurons in the reward-predicting manner and CD neurons in turn modulate saccade parameters with their polysynaptic connections to the oculomotor brain stem.

Animals↗

NEOBASE: databasing the neocortical microcircuit.

Mammals adapt to a rapidly changing world because of the sophisticated perceptual and cognitive function enabled by the neocortex. The neocortex, which has expanded to constitute nearly 80% of the human brain seems to have arisen from repeated duplication of a stereotypical template of neurons and synaptic circuits with subtle specializations in different brain regions and species. Determining the design and function of this microcircuitry is therefore of paramount importance to understanding normal and abnormal higher brain function. Recent advances in recording synaptically-coupled neurons has allowed rapid dissection of the neocortical microcircuitry thus yielding a massive amount of quantitative anatomical, electrical and gene expression data on the neurons and the synaptic circuits that connect the neurons. Due to the availability of the above mentioned data, it has now become imperative to database the neurons of the microcircuit and their synaptic connections. The NEOBASE project, aims to archive the neocortical microcircuit data in a manner that facilitates development of advanced data mining applications, statistical and bioinformatics analyses tools, custom microcircuit builders, and visualization and simulation applications. The database architecture is based on ROOT, a software environment that allows the construction of an object oriented database with numerous relational capabilities. The proposed architecture allows construction of a database that closely mimics the architecture of the real microcircuit, which facilitates the interface with virtually any application, allows for data format evolution, and aims for full interoperability with other databases. NEOBASE will provide an important resource and research tool for studying the microcircuit basis of normal and abnormal neocortical function. The database will be available to local as well as remote users using Grid based tools and technologies.

Animals↗

Selective reduction by dopamine of excitatory synaptic inputs to pyramidal neurons in primate prefrontal cortex.

We have employed in vitro physiological methods to investigate dopaminergic modulation of excitatory synaptic transmission in monkey prefrontal cortex (PFC) circuits. We show that combined activation of D1-like and D2-like dopamine receptors results in the reduction of extracellular stimulation-evoked isolated EPSCs in layer 3 pyramidal neurons. Using paired recordings from synaptically connected pyramidal neurons we have determined the basic properties of unitary synaptic connections between layer 3 pyramids in the primate PFC and, interestingly, we found that dopamine does not reduce synaptic transmission between nearby pairs of synaptically coupled PFC pyramidal neurons. This input specificity may be a critical aspect of the dopaminergic regulation of recurrent excitatory circuits in the PFC.

Animals↗

Interaction foci, information synthesis, and mental activity.

The cerebral organization of mental activity is based on neural integration, specialization of functions, and the combination of rigid and flexible connections. These principles are embodied in dynamic structures, interaction foci that are detectable in the cortex during intellectual activity by means of the intracortical interaction mapping technique. Interaction foci comprise centers of cortical connections. A focus consists of neuronal groups connected by rigid connections, based on structural changes in the synapses. Each of the groups has its own frequency characteristics and is connected by flexible connections constructed on the principle of iso-lability, with neural elements at the periphery which are isorhythmic to it. The construction of interaction focus supports the synthesis of information arriving from sense organs and centers of motivations, and extractable from memory. Information synthesis underlies mental functions, the cerebral basis for which includes a rigid nucleus and a system of peripheral connections, the configuration of which may vary, thus controlling the uniqueness of a given mental experience. The principle of specialization of functions is manifested in the fact that the topography of interaction foci varies for different mental acts. In the case of perception the projection cortex is the integration center; in the case of thinking, the associative zones of the cortex are the integrative center. Imaginal thinking is primarily associated with the parietotemporal, and abstract thinking with the frontal, divisions of the cortex. Evidently, the two principle functions of consciousness are also spatially separated: integration of the "Self", which includes the volitional principle, and communication.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

The 196G/A (val66met) polymorphism of the BDNF gene is significantly associated with binge eating behavior in women with bulimia nervosa or binge eating disorder.

The brain-derived neurotrophic factor (BDNF) is involved not only in promoting neuronal outgrowth and differentiation, synaptic connectivity and neuronal repair, but also in modulating eating behavior. Since genetic factors likely contribute to the biological vulnerability to bulimia nervosa (BN) and binge eating disorder (BED), we investigated whether the functional 196G/A single nucleotide polymorphism (SNP) of the BDNF gene was associated to BN and/or BED or to some phenotypic aspects of the disordered eating. Two hundred and ten Caucasian women (126 with BN, 84 with BED and 121 healthy controls) participated into the study. No significant differences were found in the frequencies of the 196G/A variants of the BDNF gene among patients with BN or BED and healthy controls. In both BN and BED groups, subjects carrying the 196A/A genotype exhibited a weekly frequency of bingeing and a severity of binge eating (as assessed by the Bulimia Investigation Test Edinburgh) significantly higher than those with the 196A/G and 196G/G genotypes. These results suggest that the 196G/A SNP of the human BDNF gene does not contribute to the genetic susceptibility to BN and BED, but may predispose those patients to a more severe binge eating behavior.

Amino Acid Substitution↗

Significance of extracellular potassium in central respiratory control studied in the isolated brainstem-spinal cord preparation of the neonatal rat.

The significance of extracellular potassium in central respiratory control was investigated using the isolated brainstem-spinal cord preparation of the neonatal rat. Depth profiles of extracellular potassium activity ([K+])ECF in the medulla were measured with ion-sensitive microelectrodes. Although [K+]ECF increased with depth in medullary tissue during control (4 mM) and low (1 mM) potassium concentration ([K+])CSF superfusion, this gradient disappeared with higher [K+]CSF. With low [K+]CSF (1 mM), respiratory CO2 responsiveness was abolished, and increased with high [K+]CSF (8 mM). Respiratory frequency (fR) was diminished at low [K+]CSF (1 mM), and increased with elevated [K+]CSF (8 and 16 mM); with yet higher [K+]CSF (32 mM) apnea occurred after a transient increase in fR. Perforated patch recording revealed that high [K+]ECF decreased membrane resistance, depolarized membrane potential, and increased firing frequency in most of the recorded medullary neurons. High [K+]ECF also increased excitatory and inhibitory post-synaptic potentials of medullary neurons and augmented the functional connectivity among neurons. It is concluded that [K+]ECF is of importance in the maintenance of respiratory rhythm and central chemosensitivity.

Analysis of Variance↗

Growth and differentiation of cerebellar suspensions transplanted into the adult cerebellum of mice with heredodegenerative ataxia.

Cell suspensions from cerebellar primordia of 12-day mouse embryos were grafted into the cerebellum of 4-month-old Purkinje cell degeneration (pcd) mutant mice and examined 2-3 months later. In contrast to those of nontreated mutants, all of the grafted cerebella exhibited Purkinje cells that had migrated into the molecular layer, where they were clustered over its superficial two-thirds. These Purkinje cells develop flattened dendritic trees perpendicular to bundles of parallel fibers. Ultrastructural examination of their synaptic inputs and outputs disclosed that (i) as in normal cerebella, climbing fibers and axons from basket and stellate cells synapse on thick dendrites, whereas parallel fibers almost exclusively contact the distal spiny branchlets, and (ii) a substantial number of Purkinje cell axons reach their appropriate targets in the deep cerebellar nuclei, where they establish synaptic connections on large and small neurons. These results indicate that embryonic Purkinje cells grafted into the cerebellum of adult mice with heredodegenerative ataxia integrate themselves very specifically into the cerebellar circuitry of the recipient mouse, where they can replace the missing Purkinje cells. They also provide a morphological basis favoring the notion of functional restorative capabilities of neural grafts in systems in which neurons are connected in an almost point-to-point manner.

Animals↗