Afferent nerve fibres in the wall of the rat urinary bladder.

Structure and distribution of afferent nerve fibres in the rat bladder were studied by fluorescence microscopy after selective staining with antibodies against neuropeptide CGRP. Afferent fibres are very abundant (by comparison with other viscera) and interconnected in all bladder parts: muscle, urothelium, connective tissue, blood vessels, serosa. Their highest concentration is beneath the urothelium in equatorial and caudal regions, where they form a plexus, while individually maintaining a tree-like structure with innumerable branches running without preferential orientation. In cranial regions, mucosal afferent fibres become rare or absent. Abundant fibres are found in the detrusor, within each muscle bundle, with long strings of varicosities parallel to muscle cells. Afferent fibres, invariably varicose over hundreds of micrometres of their terminal parts and while still branching, comprise chains of hundreds of varicosities. Varicosities are irregular in size, frequency and separation, without specialised terminal structures around them, or within or around the fibre's ending. The possibility that varicosities are transduction points for sensory inputs is discussed, with the implication of a process taking place over considerable length in each branch of each fibre. Interconnectedness of afferent nerves of various bladder tissues, distribution of varicosities over hundreds of micrometres along axonal branches, absence of clear target structures for the fibres, apparent irregularity in the size and sequence of varicosities suggest an innervation that is not rigidly wired with distinct sensory pathways. In fact, the structural evidence suggests extensive afferent integration at the periphery, with wide distribution of source points and broad range of physical detectors.

Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing.SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the granule cell layer.

Interlayer Repulsion of Retinal Ganglion Cell Mosaics Regulates Spatial Organization of Functional Maps in the Visual Cortex.

In higher mammals, orientation tuning of neurons is organized into a quasi-periodic pattern in the primary visual cortex. Our previous model studies suggested that the topography of cortical orientation maps may originate from moiré interference of ON and OFF retinal ganglion cell (RGC) mosaics, but did not account for how the consistent spatial period of maps could be achieved. Here we address this issue with two crucial findings on the development of RGC mosaics: first, homotypic local repulsion between RGCs can develop a long-range hexagonal periodicity. Second, heterotypic interaction restrains the alignment of ON and OFF mosaics, and generates a periodic interference pattern map with consistent spatial frequency. To validate our model, we quantitatively analyzed the RGC mosaics in cat data, and confirmed that the observed retinal mosaics showed evidence of heterotypic interactions, contrary to the previous view that ON and OFF mosaics are developed independently.SIGNIFICANCE STATEMENT Orientation map is one of the most studied functional maps in the brain, but it has remained unanswered how the consistent spatial periodicity of maps could be developed. In the current study, we address this issue with our developmental model for the retinal origin of orientation map. We showed that local repulsive interactions between retinal ganglion cells (RGCs) can develop a hexagonal periodicity in the RGC mosaics and restrict the alignment between ON and OFF mosaics, so that they generate a periodic pattern with consistent spatial frequency for both the RGC mosaics and the cortical orientation maps. Our results demonstrate that the organization of functional maps in visual cortex, including its structural consistency, may be constrained by a retinal blueprint.

Elaboration and Innervation of the Vibrissal System in the Rock Hyrax (Procavia capensis).

Mammalian tactile hairs are commonly found on specific, restricted regions of the body, but Florida manatees represent a unique exception, exhibiting follicle-sinus complexes (FSCs, also known as vibrissae or tactile hairs) on their entire body. The orders Sirenia (including manatees and dugongs) and Hyracoidea (hyraxes) are thought to have diverged approximately 60 million years ago, yet hyraxes are among the closest relatives to sirenians. We investigated the possibility that hyraxes, like manatees, are tactile specialists with vibrissae that cover the entire postfacial body. Previous studies suggested that rock hyraxes possess postfacial vibrissae in addition to pelage hair, but this observation was not verified through histological examination. Using a detailed immunohistochemical analysis, we characterized the gross morphology, innervation and mechanoreceptors present in FSCs sampled from facial and postfacial vibrissae body regions to determine that the long postfacial hairs on the hyrax body are in fact true vibrissae. The types and relative densities of mechanoreceptors associated with each FSC also appeared to be relatively consistent between facial and postfacial FSCs. The presence of vibrissae covering the hyrax body presumably facilitates navigation in the dark caves and rocky crevices of the hyrax's environment where visual cues are limited, and may alert the animal to predatory or conspecific threats approaching the body. Furthermore, the presence of vibrissae on the postfacial body in both manatees and hyraxes indicates that this distribution may represent the ancestral condition for the supraorder Paenungulata.

Whisker-related circuitry in the trigeminal nucleus principalis: ultrastructure.

Trigeminal (V) nucleus principalis (PrV) is the requisite brainstem nucleus in the whisker-to-barrel cortex model system that is widely used to reveal mechanisms of map formation and information processing. Yet, little is known of the actual PrV circuitry. In the ventral "barrelette" portion of the adult mouse PrV, relationships between V primary afferent terminals, thalamic-projecting PrV neurons, and gamma-aminobutyric acid (GABA)-ergic terminals were analyzed in the electron microscope. Primary afferents, thalamic-projecting cells, and GABAergic terminals were labeled, respectively, by Neurobiotin injections in the V ganglion, horseradish peroxidase injections in the thalamus, and postembedding immunogold histochemistry. Primary afferent terminals (Neurobiotin- and glutamate-immunoreactive) display asymmetric and multiple synapses predominantly upon the distal dendrites and spines of PrV cells that project to the thalamus. Primary afferents also synapse upon GABAergic terminals. GABAergic terminals display symmetric synapses onto primary afferent terminals, the somata and dendrites (distal, mostly) of thalamic-projecting neurons, and GABAergic dendrites. Thus, primary afferent inputs through the PrV are subject to pre- and postsynaptic GABAergic influences. As such, circuitry exists in PrV "barrelettes" for primary afferents to directly activate thalamic-projecting and inhibitory local circuit cells. The latter are synaptically associated with themselves, the primary afferents, and with the thalamic-projecting neurons. Thus, whisker-related primary afferent inputs through PrV projection neurons are pre- and postsynaptically modulated by local circuits.

Time disparity sensitive behavior and its neural substrates of a pulse-type gymnotiform electric fish, Brachyhypopomus gauderio.

Roles of the time coding electrosensory system in the novelty responses of a pulse-type gymnotiform electric fish, Brachyhypopomus, were examined behaviorally, physiologically, and anatomically. Brachyhypopomus responded with the novelty responses to small changes (100 µs) in time difference between electrosensory stimulus pulses applied to different parts of the body, as long as these pulses were given within a time period of ~500 µs. Physiological recording revealed neurons in the hindbrain and midbrain that fire action potentials time-locked to stimulus pulses with short latency (500-900 µs). These time-locked neurons, along with other types of neurons, were labeled with intracellular and extracellular marker injection techniques. Light and electron microscopy of the labeled materials revealed neural connectivity within the time coding system. Two types of time-locked neurons, the pear-shaped cells and the large cells converge onto the small cells in a hypertrophied structure, the mesencephalic magnocellular nucleus. The small cells receive a calyx synapse from a large cell at their somata and an input from a pear-shaped cell at the tip of their dendrites via synaptic islands. The small cells project to the torus semicircularis. We hypothesized that the time-locked neural signals conveyed by the pear-shaped cells and the large cells are decoded by the small cells for detection of time shifts occurring across body areas.

An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension.

Glucocorticoid excess causes insulin resistance and hypertension. Hepatic expression of PPARalpha (Ppara) is required for glucocorticoid-induced insulin resistance. Here we demonstrate that afferent fibers of the vagus nerve interface with hepatic Ppara expression to disrupt blood pressure and glucose homeostasis in response to glucocorticoids. Selective hepatic vagotomy decreased hyperglycemia, hyperinsulinemia, hepatic insulin resistance, Ppara expression, and phosphoenolpyruvate carboxykinase (PEPCK) enzyme activity in dexamethasone-treated Ppara(+/+) mice. Selective vagotomy also decreased blood pressure, adrenergic tone, renin activity, and urinary sodium retention in these mice. Hepatic reconstitution of Ppara in nondiabetic, normotensive dexamethasone-treated PPARalpha null mice increased glucose, insulin, hepatic PEPCK enzyme activity, blood pressure, and renin activity in sham-operated animals but not hepatic-vagotomized animals. Disruption of vagal afferent fibers by chemical or surgical means prevented glucocorticoid-induced metabolic derangements. We conclude that a dynamic interaction between hepatic Ppara expression and a vagal afferent pathway is essential for glucocorticoid induction of diabetes and hypertension.

[Super-resolution optical microscopy of the organ of Corti. Investigations on the fine structure of the inner hair cell afferent synapse by the 4Pi and STED techniques]. / Höchstauflösende optische Mikroskopie am Corti-Organ. Feinstrukturaufklärung an der afferenten Synapse innerer Haarzellen mittels 4Pi- und STED-Technik.

BACKGROUND: Inner hair cells encode sound into action potentials in the auditory nerve. Spiral ganglion neurons form the afferent innervation of inner hair cells via the hair cell synapse. The structure and function of this ribbon-type synapse is considered to have a major impact on the sound encoding process itself. In this study we have used conventional confocal microscopy as well as super-resolution techniques to investigate the synaptic organization in the inner hair cells of mice. MATERIAL AND METHODS: Functionally relevant proteins of the afferent inner hair cell synapse were selectively marked using immunohistochemical methods and investigated with conventional confocal and super-resolution 4Pi- and stimulated emission depletion (STED) techniques. RESULTS: Synapse and innervation density was mapped over the entire tonotopic axis. We found inner hair cells in the region of best hearing to have about twice the number of afferent fibres compared to the apex or base of the cochlea. For the first time 4Pi and STED microscopic techniques were employed to resolve the fine structure of these synapses beyond the resolution of conventional light microscopy. With 4Pi a resolution of approximately 100 nm in the z-axis direction is feasible. In practice STED delivers an effective resolution between 150 and 30 nm, depending on the power of the lasers employed. Synapses at different tonotopic positions of the cochlea exhibit no relevant structural differences at this level of resolution. The 4Pi and STED microscopic techniques are capable of showing the structure of afferent synapses in the organ of Corti with unsurpassed resolution. These images contribute to our understanding of sound-encoding mechanisms in the inner ear.

Cortical and thalamic innervation of direct and indirect pathway medium-sized spiny neurons in mouse striatum.

The striatum receives major excitatory inputs from the cortex and thalamus that predominantly target the spines of medium-sized spiny neurons (MSNs). We aimed to determine whether there is any selectivity of these two excitatory afferents in their innervation of direct and indirect pathway MSNs. To address this, we used bacterial artificial chromosome transgenic mice, in which enhanced green fluorescent protein (EGFP) reports the presence of D(1) or D(2) dopamine receptor subtypes, markers of direct and indirect pathway MSNs, respectively. Excitatory afferents were identified by the selective expression of vesicular glutamate transporter type 1 (VGluT1) by corticostriatal afferents and vesicular glutamate transporter type 2 (VGluT2) by thalamostriatal afferents. A quantitative electron microscopic analysis was performed on striatal tissue from D(1) and D(2) mice that was double immunolabeled to reveal the EGFP and VGluT1 or VGluT2. We found that the proportion of synapses formed by terminals derived from the cortex and thalamus was similar for both direct and indirect pathway MSNs. Furthermore, qualitative analysis revealed that individual cortical or thalamic terminals form synapses with both direct and indirect pathway MSNs. Similarly, we observed a convergence of cortical and thalamic inputs onto individual MSNs of both direct and indirect pathway: individual EGFP-positive structures received input from both VGluT2-positive and VGluT2-negative terminals. These findings demonstrate that direct and indirect pathway MSNs are similarly innervated by cortical and thalamic afferents; both projections are thus likely to be critical in the control of MSNs and hence play fundamental roles in the expression of basal ganglia function.

Dendritic spines, synaptic plasticity and neuronal survival: activity shapes dendritic spines to enhance neuronal viability.

An emerging view of structure-function relations of synapses in central spiny neurons asserts that larger spines produce large synaptic currents and that these large spines are persistent ('memory') compared to small spines which are transient. Furthermore, 'learning' involves enlargement of small spine heads and their conversion to being large and stable. It is also assumed that the number of spines, hence the number of synapses, is reflected in the frequency of miniature excitatory postsynaptic currents (mEPSCs). Consequently, there is an assumption that the size and number of mEPSCs are closely correlated with, respectively, the physical size of synapses and number of spines. However, several recent observations do not conform to these generalizations, necessitating a reassessment of the model: spine dimension and synaptic responses are not always correlated. It is proposed that spines are formed and shaped by ongoing network activity, not necessarily by a 'learning' event, to the extent that, in the absence of such activity, new spines are not formed and existing ones disappear or convert into thin filopodia. In the absence of spines, neurons can still maintain synapses with afferent fibers, which can now terminate on its dendritic shaft. Shaft synapses are likely to produce larger synaptic currents than spine synapses. Following loss of their spines, neurons are less able to cope with the large synaptic inputs impinging on their dendritic shafts, and these inputs may lead to their eventual death. Thus, dendritic spines protect neurons from synaptic activity-induced rises in intracellular calcium concentrations.

Central projections of primary sensory afferents to the spinal dorsal horn in the long-tailed stingray, Himantura fai.

The central projections of primary sensory afferents innervating the caudal region of the pectoral fin of the long-tailed stingray (Himantura fai) were labeled by applying the lipophilic carbocyanine dye DiI to the dorsal roots in fixed tissue. These observations were complemented by examination of hemotoxylin and eosin-stained paraffin sections of the dorsal root entry zone, and transmission electron microscopy of the dorsal horn. Transverse sections of the sensory nerve and dorsal root revealed two distinct myelinated axon sizes in the sensory nerve. Although the thick and thin axons do not appear to group together in the sensory nerves and dorsal root, they segregate into a dorsally directed bundle of thin fibers and a more horizontally directed bundle of thick fibers soon after entering the spinal cord. In DiI-labeled horizontal sections, fibers were observed to enter the spinal cord and diverge into rostrally and caudally directed trajectories. Branching varicose axons could be traced in the dorsal horn gray matter in the segment of entry and about half of the adjacent rostral and caudal segments. In transverse and sagittal sections, DiI-labeled afferents were seen to innervate the superficial and, to a lesser extent, deeper laminae of the dorsal horn, but not the ventral horn. Electron microscopy of unlabeled dorsal horn sections revealed a variety of synaptic morphologies including large presynaptic elements (some containing dense-core vesicles) making synaptic contacts with multiple processes in a glomerular arrangement; in this respect, the synaptic ultrastructure is broadly similar to that seen in the dorsal horn of rodents and other mammals.

Selective GABAergic control of higher-order thalamic relays.

GABAergic signaling is central to the function of the thalamus and has been traditionally attributed primarily to the nucleus reticularis thalami (nRT). Here we present a GABAergic pathway, distinct from the nRT, that exerts a powerful inhibitory effect selectively in higher-order thalamic relays of the rat. Axons originating in the anterior pretectal nucleus (APT) innervated the proximal dendrites of relay cells via large GABAergic terminals with multiple release sites. Stimulation of the APT in an in vitro slice preparation revealed a GABA(A) receptor-mediated, monosynaptic IPSC in relay cells. Activation of presumed single APT fibers induced rebound burst firing in relay cells. Different APT neurons recorded in vivo displayed fast bursting, tonic, or rhythmic firing. Our data suggest that selective extrareticular GABAergic control of relay cell activity will result in effective, state-dependent gating of thalamocortical information transfer in higher-order but not in first-order relays.

Dendritic spine heterogeneity determines afferent-specific Hebbian plasticity in the amygdala.

Functional compartmentalization of dendrites is thought to underlie afferent-specific integration of neural activity in laminar brain structures. Here we show that in the lateral nucleus of the amygdala (LA), an area lacking apparent laminar organization, thalamic and cortical afferents converge on the same dendrites, contacting neighboring but morphologically and functionally distinct spine types. Large spines contacted by thalamic afferents exhibited larger Ca(2+) transients during action potential backpropagation than did small spines contacted by cortical afferents. Accordingly, induction of Hebbian plasticity, dependent on postsynaptic spikes, was restricted to thalamic afferents. This synapse-specific effect involved activation of R-type voltage-dependent Ca(2+) channels preferentially located at thalamic inputs. These results indicate that afferent-specific mechanisms of postsynaptic, associative Hebbian plasticity in LA projection neurons depend on local, spine-specific morphological and molecular properties, rather than global differences between dendritic compartments.

In DRG11 knock-out mice, trigeminal cell death is extensive and does not account for failed brainstem patterning.

A previous study (Ding et al., 2003) showed that the homeodomain transcription factor DRG11 is necessary for pattern formation in the trigeminal nucleus principalis (PrV), the requisite brainstem nucleus for development of the whisker-to-barrel cortex pathway. However, it is not known how DRG11 contributes to pattern formation. Anatomical studies were performed in DRG11 knock-out (-/-) and DRG11/Bax double -/- mice to test the hypotheses that DRG11 is required for neuronal survival in the V pathway and that PrV cell death is sufficient to explain pattern alterations. At birth, DRG11(-/-) mice had equivalent cell loss in the V ganglion, PrV, and spinal V subnucleus interpolaris (SpVi). Because whisker-related patterns were normal in the SpVi, cell death would not appear to explain failed pattern formation in the mutant PrV. Electron microscopy revealed exuberant apoptosis and necrosis as the mechanisms of PrV cell death occurring in the late prenatal and newborn DRG11(-/-), when such cell death was up to six times more prevalent than normal. DRG11 heterozygote and Bax(-/-) mice were crossed in an attempt to dissociate PrV patterning anomalies from exuberant apoptosis in DRG11(-/-) mice. Both DRG11(-/-) and DRG11/Bax double -/- mutants lacked whisker-related patterning in their PrV, despite Bax(-/-)-induced rescue of V ganglion and PrV cells. Thus, apoptotic cell death is not a sufficient cause of failed pattern formation in the PrV of the DRG11(-/-). A signaling pathway involving DRG11 may, therefore, be the elusive PrV pattern maker.

Contrasting the functional properties of GABAergic axon terminals with single and multiple synapses in the thalamus.

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one "extrareticular" input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The contrasting synaptic arrangements of the two pathways were paralleled by different short-term plasticities. The multisite APT-thalamic pathway showed larger charge transfer during 50-100 Hz stimulation compared with the nRT pathway and a greater persistent inhibition accruing during stimulation trains. Our results demonstrate that the two inhibitory systems are morpho-functionally distinct and suggest and that multisite GABAergic terminals are tailored for maintained synaptic inhibition even at high presynaptic firing rates. These data explain the efficacy of extrareticular inhibition in timing relay cell activity in sensory and motor thalamic nuclei. Finally, based on the classic nomenclature and the difference between reticular and extrareticular terminals, we define a novel, multisite GABAergic terminal type (F3) in the thalamus.

Nonselective innervation of lamina I projection neurons by cocaine- and amphetamine-regulated transcript peptide (CART)-immunoreactive fibres in the rat spinal dorsal horn.

Cocaine- and amphetamine-regulated transcript (CART) peptides have been implicated in spinal pain transmission. A dense plexus of CART-immunoreactive fibres has been described in the superficial laminae of the spinal cord, which are key areas in sensory information and pain processing. We demonstrated previously that the majority of these fibres originate from nociceptive primary afferents. Using tract tracing, multiple immunofluorescent labelling and electronmicroscopy we determined the proportion of peptidergic primary afferents expressing CART, looked for evidence for coexistence of CART with galanin in these afferents in lamina I and examined their targets. Almost all (97.9%) randomly selected calcitonin gene-related peptide (CGRP)-immunoreactive terminals were substance P (SP)-positive (+) and CART was detected in approximately half (48.6%) of them. Most (81.4%) of the CGRP/SPergic boutons were galanin+ and approximately half (49.0%) of these contained CART. Many (72.9%) of the CARTergic boutons which expressed CGRP were also immunoreactive for galanin, while only 8.6% of the CARTergic terminals were galanin+ without CGRP. Electron microscopy showed that most of the CART terminals formed asymmetrical synapses, mainly with dendrites. All different morphological and neurochemical subtypes of spinoparabrachial projection neurons in the lamina I received contacts from CART-immunoreactive nociceptive afferents. The innervation density from these boutons did not differ significantly between either the different neurochemical or the morphological subclasses of these cells. This suggests a nonselective innervation of lamina I projection neurons from a subpopulation of CGRP/SP afferents containing CART peptide. These results provide anatomical evidence for involvement of CART peptide in spinal pain transmission.

Group I metabotropic glutamate receptors in the primate motor thalamus: subsynaptic association with cortical and sub-cortical glutamatergic afferents.

Preclinical evidence indicates that mGluR5 is a potential therapeutic target for Parkinson's disease and L-DOPA-induced dyskinesia. However, the mechanisms through which these therapeutic benefits are mediated remain poorly understood. Although the regulatory role of mGluR5 on glutamatergic transmission has been examined in various basal ganglia nuclei, very little is known about the localization and function of mGluR5 in the ventral motor and intralaminar thalamic nuclei, the main targets of basal ganglia output in mammals. Thus, we used immuno-electron microscopy to map the cellular and subcellular localization of group I mGluRs (mGluR1a and mGluR5) in the ventral motor and caudal intralaminar thalamic nuclei in rhesus monkeys. Furthermore, using double immuno-electron microscopy, we examined the subsynaptic localization of mGluR5 in relation to cortical and sub-cortical glutamatergic afferents. Four major conclusions can be drawn from these data. First, mGluR1a and mGluR5 are expressed postsynaptically on the plasma membrane of dendrites of projection neurons and GABAergic interneurons in the basal ganglia- and cerebellar-receiving regions of the ventral motor thalamus and in CM. Second, the plasma membrane-bound mGluR5 immunoreactivity is preferentially expressed perisynaptically at the edges of cortical and sub-cortical glutamatergic afferents. Third, the mGluR5 immunoreactivity is more strongly expressed in the lateral than the medial tiers of CM, suggesting a preferential association with thalamocortical over thalamostriatal neurons in the primate CM. Overall, mGluR5 is located to subserve powerful modulatory role of cortical and subcortical glutamatergic transmission in the primate ventral motor thalamus and CM.

Early axonal contacts during development of an identified dendrite in the brain of the zebrafish.

We have identified the initial synaptic contacts made onto the Mauthner (M) cell, an identified neuron that arises during early development of the zebrafish hindbrain. The contacts are made by a small bundle of pioneering trigeminal sensory axons onto the M cell soma before it forms dendrites. The sensory bundle is then partially enveloped by the M cell. The lateral dendrite appears at about the site of the contact, and eventually the trigeminal inputs are shifted to its trunk. As the dendrite elongates, other sensory contacts are made on its distal regions, sequentially from the acoustico-vestibular nerve and the lateral line nerves. To learn whether the earliest inputs induce the initial outgrowth of the M cell dendrite, we ablated the trigeminal neurons by laser irradiation before they contacted the M cell. Morphogenesis of the M cell, including its dendrite, appeared normal.

Selective dopamine filter of glutamate striatal afferents.

Corticostriatal glutamate afferents and mesostriatal dopamine afferents commonly converge onto the same postsynaptic spines of medium projection neurons. The consequent synaptic triad provides an ideal configuration for dopamine modulation of glutamatergic transmission. In this issue of Neuron, Bamford et al. report that dopamine inhibits glutamate release in a selective manner by activating presynaptic D2 receptors.

Laminar specificity of extrinsic cortical connections studied in coculture preparations.

The formation of specific neural connections in the cerebral cortex was studied using organotypic coculture preparations composed of subcortical and cortical regions. Morphological and electrophysiological analysis indicated that several cortical efferent and afferent connections, such as the corticothalamic, thalamocortical, corticocortical, and corticotectal connections, were established in the cocultures with essentially the same laminar specificity as that found in the adult cerebral cortex, but without specificity of sensory modality. This suggests the existence of a cell-cell recognition system between cortical or subcortical neurons and their final targets. This interaction produces lamina-specific connections, but is probably insufficient for the formation of the modality-specific connections.