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Expression of calretinin in diverse neuronal populations during development of rat hippocampus.

The prenatal and postnatal expression of calretinin was studied in hippocampus of the rat using immunohistochemical procedures. Calretinin was detected as early as embryonic day 15 in the primordial hippocampus where calretinin-containing neurons and fibres were localized to the primitive plexiform layer. Upon emergence of the hippocampal plate (the prospective stratum pyramidale), large numbers of immunopositive multipolar cells were observed in the marginal zone. Fewer cells with fusiform cell bodies were observed bordering the hippocampal plate and subplate. During the perinatal period (embryonic day 20 to postnatal day 0), large numbers of immunoreactive pyramidal-like neurons were observed at the margin of the hippocampal plate with the subplate. At this same time, many calretinin-containing neurons with irregularly shaped dendrites were observed in stratum radiatum. Soon after birth (postnatal day 3), the calretinin immunoreactivity of both these later cell types rapidly declined and a new population of calretinin-immunopositive cells emerged, the Cajal-Retzius cells of stratum lacunosum-moleculare and the dentate gyrus. The Cajal-Retzius cells rapidly matured but disappeared by the second postnatal week. During the second postnatal week, calretinin interneurons of the adult hippocampal formation began to appear. Their immunoreactivity increased by postnatal day 15, when the number of calretinin-immunopositive interneurons in area CA1 and stratum radiatum of CA3 exceeded that of the adult. At this time, the soma and proximal dendrites of many calretinin interneurons were found to contact each other. The frequency of such cellular appositions decreased in adulthood. The results presented here show that calretinin immunohistochemistry can be very useful in recording the development of subpopulations of hippocampal neurons that are present during distinct embryonic and postnatal periods. Although some neuronal types may exist only briefly during hippocampal development, others appear to express calretinin transiently during restricted phases of neuronal differentiation. Surprisingly, this includes some hippocampal pyramidal cells. However, even as the adult pattern of immunostaining emerges in week 2, morphological refinement of interneurons continues to take place, which eventually leads to the population of calretinin-containing interneurons of the mature hippocampus.

Animals↗

Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly.

Three classes of neurons form synapses in the antennal lobe of Drosophila, the insect counterpart of the vertebrate olfactory bulb: olfactory receptor neurons, projection neurons, and inhibitory local interneurons. We have targeted a genetically encoded optical reporter of synaptic transmission to each of these classes of neurons and visualized population responses to natural odors. The activation of an odor-specific ensemble of olfactory receptor neurons leads to the activation of a symmetric ensemble of projection neurons across the glomerular synaptic relay. Virtually all excited glomeruli receive inhibitory input from local interneurons. The extent, odor specificity, and partly interglomerular origin of this input suggest that inhibitory circuits assemble combinatorially during odor presentations. These circuits may serve as dynamic templates that extract higher order features from afferent activity patterns.

Animals↗

Excitation-neurogenesis coupling in adult neural stem/progenitor cells.

A wide variety of in vivo manipulations influence neurogenesis in the adult hippocampus. It is not known, however, if adult neural stem/progenitor cells (NPCs) can intrinsically sense excitatory neural activity and thereby implement a direct coupling between excitation and neurogenesis. Moreover, the theoretical significance of activity-dependent neurogenesis in hippocampal-type memory processing networks has not been explored. Here we demonstrate that excitatory stimuli act directly on adult hippocampal NPCs to favor neuron production. The excitation is sensed via Ca(v)1.2/1.3 (L-type) Ca(2+) channels and NMDA receptors on the proliferating precursors. Excitation through this pathway acts to inhibit expression of the glial fate genes Hes1 and Id2 and increase expression of NeuroD, a positive regulator of neuronal differentiation. These activity-sensing properties of the adult NPCs, when applied as an "excitation-neurogenesis coupling rule" within a Hebbian neural network, predict significant advantages for both the temporary storage and the clearance of memories.

Animals↗

Neural substrate of nicotine addiction as defined by functional brain maps of gene expression.

The distributed neural networks involved in the intravenous self-administration of nicotine and cocaine, and in a model of relapse of nicotine-taking after abstinence, were compared in Wistar rats. Post-mortem brain maps of c-fos-related antigens expression showed specific activation in prefrontal cortex, anterior cingulate and nucleus accumbens for both drugs, but of the anterior cingulate cortex only during relapse, suggesting that a subset of the neural network involved in drug self-administration is activated during relapse.

Animals↗

Morphological study of the submucosal and mucosal plexuses of the sheep forestomach.

Submucosal and mucosal nerve plexuses in the ovine forestomach were examined by immunohistochemical staining for protein gene-product 9.5 (PGP 9.5) and for S-100 protein (S-100), using whole-mount specimens that had been prepared by treatment with KOH. Nerve fibers of various sizes and glial cells (i.e., Schwann cells and satellite cells) were stained with antibodies against PGP 9.5 and S-100 respectively. The network of the submucosal plexus in the rumen is irregular and some nerve bundles in the plexus cross over other bundles. Some of the nerve bundles penetrate the ruminal papillae. The submucosal plexus in the reticulum consists of a network in the reticular wall and the reticular folds. The submucosal plexus in the omasum is also divided into two segments; namely, the sublaminar and the intralaminar plexuses. Most of the submucosal ganglion cells are unipolar and smooth-surfaced, being located singly or in small groups. A few perikarya were detected in the ruminal papillae. The number of perikarya per unit surface area is greater in the caudal portion of the omasal lamina (19.32 +/- 8.62 per cm2). In the mucosal plexuses, a well-developed network of beaded fibers with PGP 9.5-like immunoreactivity and a glial framework of S-100 like immunoreactivity was observed, in particular in the ruminal, reticular and omasal papillae. The intrapapillary nervous networks are interconnected by thin bundles of nerves in the interpapillary region. The present results suggest that some of the mucosal functions are intrinsically regulated by the submucosal and mucosal plexuses in the ovine forestomach.

Animals↗

NMDA receptor-mediated dendritic spikes and coincident signal amplification.

Dendrites of cortical neurons possess active conductances, which contribute to the nonlinear processing of synaptic information. Recently it has been shown that basal dendrites can generate highly localized spikes mediated by NMDA receptor channels. These spikes may serve as a powerful mechanism to detect and amplify synchronously activated spatially clustered excitatory synaptic inputs in individual dendritic segments, and may enable parallel processing in several integrative dendritic subunits.

Action Potentials↗

Wiring, dysmorphogenesis and epilepsy: a hypothesis.

Cerebral cortical dysgenesis has been found by magnetic resonance imaging to be the second most common pathology underlying medically refractory chronic partial epilepsy. Patients with the latter condition form the largest group in specialist epilepsy clinics. The pathogenesis of the epilepsy in cortical dysgenesis remains largely obscure. The most popular current hypothesis holds neuronal misconnection secondary to neuronal malpositioning culpable for seizure activity. However, a review of the published literature of cortical dysgenesis and an analysis of newer magnetic resonance and histopathological data, suggests that this view is no longer tenable. A modified hypothesis is proposed in which neuronal connectivity itself is postulated to be the primary motive force in both cerebral morphogenesis and epileptogenesis in cases of cortical dysgenesis. This hypothesis leads to the generation of a model for cortical development and directly testable predictions of intercellular connectivity, as well as a potential tool for the prediction of the possibility of freedom from seizure activity after surgical resection of dysgenetic lesions in individual cases.

Animals↗

Cardiorespiratory neurons of the rat ventrolateral medulla contain TASK-1 and TASK-3 channel mRNA.

The potassium channels TASK-1 and TASK-3 are neuronal 'leak' channels that are inhibited by extracellular acidification and numerous neurotransmitters. Here we tested whether in the rat TASK-1 and TASK-3 mRNAs are present in ventrolateral medulla neurons that regulate respiration or circulation (C1 adrenergic neurons). The mRNAs were identified by in situ hybridization. Respiratory neurons were identified by anatomical markers (neurokinin-1 receptors, NK1R, or somatostatin) or directly by juxtacellular labeling of bulbospinal neurons. C1 neurons were identified by the presence of tyrosine-hydroxylase. TASK-1 and TASK-3 transcripts were present in all hypoglossal and facial motor neurons, in most C1 cells (85-95%), in most small and large NK1R-ir neurons (>90%) of the ventral respiratory group (VRG) and in all the inspiratory-augmenting bulbospinal neurons of the rostral ventral respiratory group. In conclusion, TASK channels are expressed by respiratory cells with putative rhythmogenic function and by premotor and motor neurons. TASK channels presumably mediate excitatory effects of numerous transmitters on these neurons and may contribute to their pH-sensitivity.

Adrenergic Fibers↗

Presynaptic frequency- and pattern-dependent filtering.

Dual intracellular recordings from pairs of synaptically connected neurones have demonstrated that the frequency-dependent pattern of transmitter release varies dramatically between different classes of connections. Somewhat surprisingly, these patterns are not determined by the class of neurone supplying the axon alone, but to a large degree by the class of postsynaptic neurone. A wide range of presynaptic mechanisms, some that depress the release of transmitter and others that enhance release have been identified. It is the selective expression of these different mechanisms that determines the unique frequency- and pattern-dependent properties of each class of connection. Although the molecular interactions underlying these several mechanisms have yet to be fully identified, the wealth and complexity of the protein-protein and protein-lipid interactions that have been shown to control the release of transmitter suggest many ways in which the properties of a synapse may be tuned to respond to particular patterns and frequencies.

Animals↗

Functional recovery of respiratory behavior during axonal regeneration in snails (Lymnaea stagnalis) is experience dependent.

This study investigated the role of experience in recovery of pulmonary respiration during axonal regeneration in Lymnaea stagnalis. Pulmonary respiration occurs when snails break the water surface and open the lung orifice, the pneumostome. It was shown that axotomy of all the axons innervating the pneumostome and surrounding area prevents the occurrence of lung respiration in 69% of snails. In the remaining 31%, lung respiration persisted, indicating that peripheral components alone are capable of initiating pneumostome openings and closures. Five weeks postsurgery, all snails with previous nerve crushes showed opening of the pneumostome with normal latency after breaking the water surface. However, prevention of pulmonary respiration during the recovery period dramatically changed the recovered behavior. Thus, experience in pulmonary respiration during axonal regeneration plays a role in the recovery of this behavior.

Animals↗

Membrane currents that govern smooth muscle contraction in a ctenophore.

Ctenophores are transparent marine organisms that swim by means of beating cilia; they are the simplest animals with individual muscle fibres. Predatory species, such as Beroe ovata, have particularly well-developed muscles and are capable of an elaborate feeding response. When Beroe contacts its prey, the mouth opens, the body shortens, the pharynx expands, the prey is engulfed and the lips then close tightly. How this sequence, which lasts 1 s, is accomplished is unclear. The muscles concerned are structurally uniform and are innervated at each end by a neuronal nerve net with no centre for coordination. Isolated muscle cells studied under voltage-clamp provide a solution to this puzzle. We find that different groups of muscle cells have different time-dependent membrane currents. Because muscle contraction depends upon calcium entry during each action potential, these different currents produce different patterns of contraction. We conclude that in a simple animal such as a ctenophore, a sophisticated set of membrane conductances can compensate for the absence of an elaborate system of effectors.

4-Aminopyridine↗

ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin.

Networks in the CNS consist of neural modules that are connected in a repetitive array. Whereas individual modules contain guidance information along which axons track within the unit, these guidance cues hinder axon extension across module boundaries. We investigated how axons solve this 'boundary problem' by analyzing the longitudinal connections of neuromeres in Drosophila melanogaster. The initial trajectory of the longitudinal axons is guided by Netrin, which is localized on commissural axons by its receptor, Frazzled. The Netrin cue on the commissure of the next segment can act as a barrier to longitudinal axons, inhibiting their extension and misguiding them contralaterally along the commissure. We show that, before reaching the segmental boundary, the longitudinal axons' responsiveness to Netrin presented on the commissure is suppressed by Roundabout (ROBO), through counteracting Gq signaling. The absence of suppression causes the robo phenotype: longitudinal axons project toward the midline, as if running around a roundabout (rotary).

Animals↗

Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development.

Dysfunction of the prefrontal cortex in schizophrenia may be associated with abnormalities in synaptic structure and/or function and reflected in altered concentrations of proteins in presynaptic terminals and involved in synaptic plasticity (synaptobrevin/ vesicle-associated membrane protein (VAMP), synaptosomal-associated protein-25 (SNAP-25), syntaxin, synaptophysin and growth-associated protein-43 (GAP-43)). We examined the immunoreactivity of these synapse-associated proteins via quantitative immunoblotting in the prefrontal cortex of patients with schizophrenia (n=18) and in normal controls (n=23). We also tested the stability of these proteins across successive post-mortem intervals in rat brains (at 0, 3, 12, 24, 48, and 70 h). To investigate whether experimental manipulation of prefrontal cortical development in the rat alters prefrontal synaptic protein levels, we lesioned the ventral hippocampus of rats on postnatal day 7 and measured immunoreactivity of presynaptic proteins in the prefrontal cortex on postnatal day 70. VAMP immunoreactivity was lower in the schizophrenic patients by 22% (P<0.03). There were no differences in the immunoreactivity of any other proteins measured in schizophrenic patients as compared to the matched controls. Proteins were fairly stable up to 24 h and thereafter the abundance of most proteins examined was significantly reduced (falling to as low as 20% of baseline levels at 48-70 h). VAMP immunoreactivity was higher in the lesioned rats as compared to sham controls by 22% (P&<0.03). There were no significant differences between the lesioned rats and sham animals in any other presynaptic protein. These data suggest that apparently profound prefrontal cortical dysfunction in schizophrenia, as well as in an animal model of schizophrenia, may exist without gross changes in the abundance of many synaptic proteins but discrete changes in selected presynaptic molecules may be present.

Adolescent↗

Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats.

This investigation was designed to study the spontaneous functional recovery of adult rats with incomplete spinal cord injury (SCI) at thoracic level during a time course of 2 weeks. Daily testing sessions included open field locomotor examination and electromyographic (EMG) recordings from a knee extensor (vastus lateralis, VL) and an ankle flexor muscle (tibialis anterior, TA) in the hindlimbs of treadmill walking rats. The BBB score (a locomotor score named after Basso et al., 1995, J. Neurotrauma, 12, 1-21) and various measures from EMG recordings were analysed (i.e. step cycle duration, rhythmicity of limb movements, flexor and extensor burst duration, EMG amplitude, root-mean-square, activity overlap between flexor and extensor muscles and hindlimb coupling). Directly after SCI, a marked drop in locomotor ability occurred in all rats with subsequent partial recovery over 14 days. The recovery was most pronounced during the first week. Significant changes were noted in the recovery of almost all analysed EMG measures. Within the 14 days of recovery, many of these measures approached control levels. Persistent abnormalities included a prolonged flexor burst and increased activity overlap between flexor and extensor muscles. Activity overlap between flexor and extensor muscles might be directly caused by altered descending input or by maladaptation of central pattern generating networks and/or sensory feedback.

Animals↗

Monoamine release by neurons of a primitive nervous system: an amperometric study.

We measured monoamine release from dissociated neurons of the sea pansy Renilla koellikeri, a representative of the most evolutionarily ancient animals with nervous systems, by real-time monitoring of exocytosis using the amperometric method with carbon-fiber microelectrodes. Depolarization-induced, as well as spontaneously active, neurons exhibited calcium-dependent exocytotic events at both the soma and the terminal bulb of neuritic processes. All spontaneously active neurons exhibited a bursting activity pattern in which amplitudes of exocytotic events appeared to be distributed in a quantal-like fashion. Fast Fourier transform analysis of bursting activity in 20 such neurons revealed burst harmonics with a major frequency of 8 Hz and a dominant rate of 95 Hz for individual exocytotic events within bursts. The results suggest that exocytotic transmitter release is as ancient as neurons and that endogenously bursting neurons in the sea pansy are as complex as those of higher animals. In addition, the observation that both soma and neuritic terminals of the same neuron can release transmitter suggests that local release sites in these cnidarian neurons are not critical for nerve net function.

Animals↗

Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion.

The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically associates with the Robo receptor. Too much or too little CrGAP activity leads to defects in Robo-mediated repulsion at the midline choice point. The CrGAP gain-of-function phenotype mimics the loss-of-function phenotypes of both Robo and Rac. Dosage-sensitive genetic interactions among CrGAP, Robo, and Rac support a model in which CrGAP transduces signals downstream of Robo receptor to regulate Rac-dependent cytoskeletal changes.

Animals↗