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Connections of medial preoptic neurons with the median eminence and amygdala. An electrophysiological study in the rat.

An electrophysiological investigation was conducted on the connection of medial preoptic neurons with the median eminence and the basal and corticomedial amygdala in pentobarbital anesthesized male Sprague-Dawley rats. Of 411 medial preoptic neurons tested with median eminence stimuli, antidromic responses (mean latency 11.4 +/- SEM 0.4 ms) identified 177 cells as tuberoinfundibular neurons. Most were located in the periventricular area; 21 cells were in the area of the suprachiasmatic nucleus. Axon conduction velocities ranged between 0.01 and 0.9 m/s. 16 neurons displayed two distinct antidromic latencies when the median eminence stimulus was increased above threshold, indicating that their axons may branch in the region of the median eminence. Following suprathreshold stimulation, only 10% of spontaneously active neurons displayed features to suggest activation of a recurrent inhibitory pathway. In response to amygdala stimulation, 23% of tuberoinfundibular neurons displayed an orthodromic response; most (80%) responded with an increase in excitability after a latency of 21.6 +/- 2.4 ms; the remainder displayed a decrease in excitability at latencies of 20-28 ms lasting in excess of 100 ms. These data suggest an additional neural pathway whereby the amygdala can influence neuroendocrine regulation, i.e. through its actions on the excitability of medial preoptic tuberoinfundibular neurons.

Action Potentials↗

A pair of reciprocally inhibitory histaminergic sensory neurons are activated within the same phase of ingestive motor programs in Aplysia.

Previous studies have shown that each buccal ganglion in Aplysia contains two B52 neurons, one in each hemiganglion. We now show that there are two B52 neurons in a single buccal hemiganglion and four cells in an animal. We also show that the B52 neurons are histamine-immunoreactive and use reverse phase HPLC to show that the histamine-immunoreactive substance is authentic histamine. Previous studies have shown that the B52 neurons make numerous inhibitory synaptic connections with neurons active during the radula closing/retraction phase of ingestive motor programs. A computational model of the Aplysia feeding central pattern generator has, therefore, suggested that the B52 neurons play a role in terminating closing/retraction. Consistent with this idea we show that both B52 neurons fire at the beginning of radula opening/protraction. We also show that both B52 neurons are sensory neurons. They are depolarized when a flap of connective tissue adjacent to the buccal commissural arch is stretched. During ingestive feeding this is likely to occur at the peak of closing/retraction as opening/protraction begins. In the course of this study we compare the two ipsilateral B52 neurons and show that these cells are virtually indistinguishable; e.g., they use a common neurotransmitter, make the same synaptic connections, and are both sensory as well as premotor neurons. Nevertheless we show that the B52 neurons are reciprocally inhibitory. Our results, therefore, strikingly confirm theoretical predictions made by others that neurons that inhibit each other will not necessarily participate in antagonistic phases of behavior.

Animals↗

Reciprocal connections of lateral septal neurons and neurons in the lateral hypothalamus in the rat: a combined phaseolus vulgaris-leucoagglutinin and Fluoro-Gold immunocytochemical study.

Reciprocal connections between lateral septal neurons and neurons in the lateral hypothalamus/lateral preoptic area were studied in the rat. The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde tracer Fluoro-Gold (FG) were simultaneously injected into the lateral septum. After double-immunocytochemistry, PHA-L-labeled terminals were found in synaptic contact with dendrites of retrogradely FG-labeled neurons in the lateral hypothalamic/lateral preoptic area.

Afferent Pathways↗

Fine structural studies of growth-hormone-releasing-factor (GRF)-immunoreactive neurons and their synaptic connections in the guinea pig arcuate nucleus.

The fine structure of neurons containing human growth-hormone-releasing factor (hGRF) immunoreactivity located in the arcuate nucleus of the guinea pig was studied by means of the preembedding immunohistochemical technique. The perikaryon of labeled neurons was fusiform or ovoid; the nucleus was regular in shape and contained a prominent nucleolus. The main ultrastructural features of the hGRF-immunoreactive neurons were the presence of numerous labeled secretory granules (100-120 nm in diameter) and the abundance and the enlargement of the organelles involved in the synthesis of the peptides: a well-developed rough endoplasmic reticulum and a conspicuous Golgi apparatus. Synaptic inputs were observed on immunoreactive perikarya but, above all, on the labeled dendrites. The unstained presynaptic nerve endings most often contained only small clear vesicles and formed symmetrical contacts. In rare cases, the presynaptic terminals exhibited both small clear and large dense vesicles and constituted asymmetrical contacts. Immunoreactive nerve endings were also observed in this area: the synaptic boutons contained large, stained vesicles and small, unlabeled, clear vesicles. These axon terminals made synaptic contacts with unstained dendritic processes; the contacts were symmetrical. The results indicate that hGRF-immunoreactive neurons of the guinea pig arcuate nucleus present morphological features of neuroendocrine cells. Moreover, the presence of hGRF-labeled nerve endings in the arcuate nucleus itself suggests that a substance related to hGRF might be a neuromodulator, at least in this area.

Animals↗

Brainstem neurons projecting to the rostral ventral respiratory group (VRG) in the medulla oblongata of the rat revealed by co-application of NMDA and biocytin.

Groups of neurons in the medulla and pons are essential for the rhythm generation, pattern formation and modulation of respiration. The rostral Ventral Respiratory Group (rVRG) is thought to be a crucial area for rhythm generation. Here we co-applied biocytin and NMDA in the rVRG to label retrogradely brainstem neurons reciprocally connected to a population of inspiratory neurons in the rat rVRG. The procedure excited rVRG neurons in multi-unit recordings and led to a Golgi-like labelling of distant cells presumably excited by efferents from the rVRG. Injection of biocytin without NMDA did not label neurons in distant structures. Several brainstem ipsi- and contralateral structures were found to project to the rVRG, but three major respiratory-related structures, the nucleus of the solitary tract (NTS), the parabrachialis medialis and Kölliker-Fuse nuclei (PB/KF) and the caudal VRG, which are known to project bilaterally to the rVRG, were exclusively labelled ipsilaterally, suggesting an ipsilateral excitation of these structures by the rVRG. The pathways of efferent axons from labelled neurons in the rVRG were traced rostrally towards the pons and caudally to the spinal cord. Terminal axonal arborizations were seen in the same regions where retrogradely filled neurons were found as well as in a few other motor nuclei (the dorsal vagal motor nucleus and XII nucleus). Moreover, in the NTS and the PB/KF, efferent terminal varicosities were seen closely apposed to the soma and proximal dendrites of labelled neurons, suggesting monosynaptic connections between the rVRG and these nuclei.

Animals↗

Electrophysiological relationship between claustrum and contralateral area 4 and 6 pyramidal tract neurons.

The connections between the claustrum and the contralateral motor areas were electrophysiologically investigated in cats under chloralose anesthesia. The extracellular unitary activity of 81 pyramidal tract neurons (PTNs) was recorded; 22 PTNs were inhibited by activation of the contralateral claustrum; inhibition was preceded by an early activation of 4 out of the 22 inhibited PTNs. Section of the corpus callosum abolished the contralateral claustrum effect, while the action of the ipsilateral homologous structure persisted.

Animals↗

Two neuropeptides colocalized in a command-like neuron use distinct mechanisms to enhance its fast synaptic connection.

In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia, we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size (q) and CP2 increases the calculated quantal content (m) of EPSPs. Since the PSP amplitude represents the product of q and m, the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron.

Action Potentials↗

Are ultra-slow isoperiodic oscillations in rat intergeniculate leaflet neurons dependent on reciprocal connection with its contralaterally located counterpart?

We investigated effects of the electrical lesion and/or chemical inactivation of intergeniculate leaflet (IGL) neurons on the ultra-slow isoperiodic neuronal oscillation of the contralaterally located IGL. The spontaneous extracellular activity of neurons, recorded simultaneously in both leaflets of the lateral geniculate nucleus, showed an ultradian oscillatory pattern. In all our experiments, both the electrical lesion and the inactivation of neurons via the blockade of action potential generation did not cause any changes in the neuronal activity pattern in the contralaterally located geniculate leaflet. The obtained results show that a bilateral IGL connection is not necessary for the pattern of neuronal oscillation in the IGL. Hence the functional significance of a reciprocal connection between both lateral geniculate nucleus leaflets is still an open question.

Animals↗

Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.

Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

Afferent Pathways↗

Innervation of the ring gland of Drosophila melanogaster.

In insects, peptidergic neurons of the central nervous system regulate the synthesis of the main developmental hormones. Neuropeptides involved in this neuroendocrine cascade have been identified in lepidopterans and dictyopterans. Since these organisms are not suitable for genetic research, we identified peptidergic brain neurons innervating the ring gland in Drosophila melanogaster. In larvae of Drosophila, ecdysteroids and juvenile hormones are produced by the ring gland, which is composed of the prothoracic gland, the corpus allatum, and the corpora cardiaca. Using the GAL4 enhancer trap system, we mapped those neurons of the central nervous system that innervate the ring gland. Eleven groups of neurosecretory neurons and their target tissues were identified. Five neurons of the lateral protocerebrum directly innervate the prothoracic gland or corpus allatum cells of the ring gland and are believed to regulate ecdysteroid and juvenile hormone titers. Axons of the circadian pacemaker neurons project onto dendritic fields of these five neurons. This connection might be the neuronal substrate of the circadian rhythms of molting and metamorphosis in Drosophila. Most of the neurons presented here have not been described before. The enhancer trap lines labeling them will be valuable tools for the analysis of neuronal as well as genetic regulation in insect development.

Animals↗

Highly dissimilar behaviors mediated by a multifunctional network in the marine mollusk Tritonia diomedea.

Several motor networks have now been found to be multifunctional, in which one group of neurons participates in the generation of multiple behavioral motor programs. Not surprisingly, the behaviors involved are frequently closely related, often using the same or similar muscle groups. Here we describe an interneuronal network in the marine mollusk Tritonia diomedea that is involved in producing two highly dissimilar behaviors, rhythmic, muscle-based escape swimming and nonrhythmic, cilia-mediated crawling. Several observations support this conclusion. First, the dorsal swim interneurons (DSIs) of the swim central pattern generator (CPG) directly excite Pedal neuron 21 (Pd21) and Pd5, the only identified cilia-activating efferent neurons in Tritonia. Second, stimulation of a single DSI elicits beating of the foot cilia in semi-intact preparations and crawling in intact animal treadmill preparations. Third, the DSIs fire at an elevated rate for nearly 1 hr after a swim motor program, which correlates reasonably well with the period freely behaving animals were found to crawl after they swam. Fourth, silencing the tonically active DSIs after a swim motor program substantially reduces or eliminates ongoing cilia neuron firing, indicating that the DSIs are major contributors to the synaptic input driving these cells. Finally, all of the other swim CPG neurons also connect to the cilia neurons, most monosynaptically. Taken together, these observations indicate that the Tritonia swim CPG network participates in producing both escape swimming and crawling. Given the extreme differences between these behaviors---rhythmic versus tonic, muscular versus ciliary, and brief versus prolonged--these findings reveal a striking versatility for a small multifunctional network.

Action Potentials↗

[Averaged impulse activity in a neuronal network model].

Every neuronal pool is proposed to contain identical neurons with identical interneuronal connections. A neuronal net containing two neuronal pools is considered. Two regimes are possible: 1) the asymptotically stable stationary solution of smooth equations system exists, the neuron pulses are periodical with different frequency in each pool; 2) the stationary sliding regime solution of smoothed equations exists. Periodical pulse train solution is impossible. The situation of "chaos" type is probable.

Models, Theoretical↗

Neuronal ceroid lipofuscinoses are connected at molecular level: interaction of CLN5 protein with CLN2 and CLN3.

Neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative storage diseases characterized by mental retardation, visual failure, and brain atrophy as well as accumulation of storage material in multiple cell types. The diseases are caused by mutations in the ubiquitously expressed genes, of which six are known. Herein, we report that three NCL disease forms with similar tissue pathology are connected at the molecular level: CLN5 polypeptides directly interact with the CLN2 and CLN3 proteins based on coimmunoprecipitation and in vitro binding assays. Furthermore, disease mutations in CLN5 abolished interaction with CLN2, while not affecting association with CLN3. The molecular characterization of CLN5 revealed that it was synthesized as four precursor forms, due to usage of alternative initiator methionines in translation. All forms were targeted to lysosomes and the longest form, translated from the first potential methionine, was associated with membranes. Interactions between CLN polypeptides were shown to occur with this longest, membrane-bound form of CLN5. Both intracellular targeting and posttranslational glycosylation of the polypeptides carrying human disease mutations were similar to wild-type CLN5.

Aminopeptidases↗

[The stability of the behavioral specialization of the neurons].

Constancy of connection between the activity of limbic cortex neurones and food-procuring behaviour was studied on rabbits during prolonged unit records. Comparison of activity in the first and the second halves of records was conducted according to the mean frequency during each stage of recording, the mean frequency in each of 10 selected acts of cyclic behaviour and also the probability of activation presence in these acts. It was shown, that behavioural specialization, determined by the criterion of presence of 100% cell activation in specific acts, did not change during recording. The volume of changes in the connection of neurone activity to behaviour in the process of record greatly depended on conditions of recording; at constant mean frequency of neurone activity during the whole time of recording the volume of these changes was minimal.

Action Potentials↗

Double labeling immunoelectron microscopic study on the synaptic connections between glutamic acid neurons and GABA neurons in the hippocampus of rats.

In order to explore the roles of different neurotransmitters in epileptic pathogenesis, the synaptic connections between glutamic acid (Glu) neurons and GABA neurons in normal rat hippocampus were studied by pre-embedding double labeling immunoelectron microscopy. The GABA immunoreaction was first demonstrated by chromogen DAB, then the Glu immunoreaction was demonstrated by molybdic acid-TMB method. After being stabilized by DAB-cobalt chloride, the sections were processed for electron microscopic embedding. Under electron microscope, there were many Glu immunoreaction-positive neurons in the pyramidal layer of hippocampal CA1 area and some GABA immunoreaction-positive neurons with pyramidal or polygonal perikarya in the pyramidal, polymorphic and radiant layer of CA1 area. There were also symmetric dendro-axonic synapses formed by GABA-positive dendrites and Glu-positive axons in the polymorphic layer and symmetric axo-dendrites synapses formed by GABA-positive axons and Glu-positive dendritic in the radiant layer. In addition, there were symmetric autoregulatory axo-dendritic synapses between Glu-positive axons and dendrites and autoregulatory axo-axonic synapses (both symmetric and asymmetric) between GABA-positive axons. Above mentioned results, for the first time, showed that there were complex synaptic regulatory relationships between excitatory Glu neurons and inhibitory GABA neurons in the hippocampal CA1 area, thereby, providing ultrastructural evidence for different neurotransmitters participating in epileptic pathogenesis.

Animals↗

[Excitatory interactions in the nerve nets switching on the cells of the auditory cortex and the medial geniculate body].

Crosscorrelation method was used for revealing effective monosynaptic excitatory interactions in neural networks containing simultaneously recorded neurons from different loci of auditory cortex (A1) and medial geniculate body (MGB). It was shown that (a) there were effective reciprocal excitatory connections between neurons in different loci of A1 and MGB; (b) connections between neurons in tonotopic loci of A1 and MGB and in adjacent cortical loci were the most effective; (c) connections were "divergent", i.e., one neuron in A1 (MGB) excited neurons in different loci of A1 and MGB simultaneously; (d) connections were "convergent", i. e., one neuron in A1 (MGB) was excited by neurons from different loci of A1 and MGB simultaneously. We suggest that this principles of organization of excitatory connections in thalamo-cortical networks promoted the induction of long-term changes (LTP and LTD) in excitatory synaptic efficacy and that this mechanism underlie the observed changes of receptive fields of A1 and MGB neurons induced by intracortical microstimulation.

Action Potentials↗

[Principle of neuronal organization of defensive reflexes in mollusks].

Spontaneous and evoked synaptic activity of the command neurons of the snail defensive reaction were studied by means of simultaneous intracellular recording. The spontaneous synaptic potentials and monosynaptic EPSP evoked by stimulation of presynaptic neurons were investigated. A mathematical model of a two-layered neuronal net of the defensive reaction was developed and constructed on the basis of the neurophysiological data. In this model the neurons of the afferent layer have local but overlapping receptive fields. Each afferent neuron is monosynaptically connected with all efferent neurons but the efficiency of the connections is different (each efferent neuron has the most effective connection with one afferent neuron only). The number of spikes of each afferent neuron appearing after stimulation of different points of its receptive field as well as efficiency of synaptic connections of each afferent neuron with efferent neurons are described by the normal low. Such neuronal net acquires the following principal property: different stimuli result in different one-model "excitation profiles" of efferent neurons.

Animals↗

Randomly connected sigma-pi neurons can form associator networks.

A set of sigma-pi units randomly connected to two input vectors forms a type of hetero-associator related to convolution- and matrix-based associative memories. Associations are represented as patterns of activity rather than connection strengths. Decoding the associations requires another network of sigma-pi units, with connectivity dependent on the encoding network. Learning the connectivity of the decoding network involves setting n3 parameters (where n is the size of the vectors), and can be accomplished in approximately 3e n log n presentations of random patterns. This type of network encodes information in activation values rather than in weight values, which makes the information about relationships accessible to further processing. This accessibility is essential for higher-level cognitive tasks such as analogy processing. The fact that random networks can perform useful operations makes it more plausible that these types of associative network could have arisen in the nervous systems of natural organisms during the course of evolution.

Animals↗