bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic potentials in the central terminals of locust proprioceptive afferents generated by other afferents from the same sense organ
Authors: Burrows M , Laurent G
Published: March 2018

Afferent neurons from a proprioceptor [the femoral chordotonal organ (FCO)] at the femoro-tibial joint of a locust hindleg carry patterns of spikes to the CNS in which information is coded about the positions and movements of the tibia. Intracellular recordings from the afferents of this organ as they enter the CNS reveal spikes and depolarizing post- synaptic potentials (PSPs) during voluntary or imposed movements of the joint. Some of these PSPs are generated as a result of spikes in other FCO afferents, and can be evoked experimentally by electrical stimulation of the nerve from the organ. One afferent does not appear to synapse directly on another, but instead activates reliable pathways involving other central neurons. Current clamping of individual afferents in isolated ganglia shows that the PSPs are increased in amplitude by hyperpolarizing currents injected into an afferent, and decreased by depolarizing ones. They reverse at about -68 mV (n = 5). At the normal resting potential of the afferents, -72 mV (+/- 0.42 SE, n = 57), the PSPs are therefore depolarizing, and are associated with an increased conductance of the membrane. The changes in membrane potential and conductances associated with the PSPs can be mimicked by pressure injection of GABA into the regions of neuropil that contain the terminals of the afferents. The potential evoked by GABA is associated with an increased conductance of the membrane and reverses at the same potential as the PSPs. GABA also reduces the PSPs evoked in the terminals, either by movements of the FCO or by electrical stimulation of its nerve. The PSPs and the effects of the GABA-evoked potentials are mimicked by the GABA agonist muscimol. The PSPs are blocked reversibly by picrotoxin. The PSPs and the GABA-evoked potentials both alter the excitability of an afferent terminal by reducing the ability of the membrane to support an action potential. It is suggested that the PSPs are depolarizing, inhibitory potentials generated in the terminals of the afferents by central neurons that release GABA, and that their role is to change the efficacy of the afferent spikes at their first output synapses in the CNS. These interactions could form a graded, gain control mechanism for synaptic transmission at the afferent output synapses that is directly dependent on the features of the mechanical movements of the joint.
The Drosophila gene rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous system-specific in both flies and humans
Authors: Kim YJ , Baker BS
Published: March 2018

The rbp9 gene of Drosophila melanogaster has been molecularly characterized and shown to be expressed solely in the CNS, where it encodes proteins with three RNA recognition motifs (RRMs). Sequencing of genomic and cDNA clones of rbp9 revealed a complex gene with three alternative promoters as well as alternative patterns of splicing. The deduced amino acid sequence of the RBP9 proteins is highly similar to those of three other nervous system-specific genes, human HuC and HuD and Drosophila elav, which also encode proteins with three RRMs. Developmental Northern analysis revealed that rbp9 is expressed from the late third instar larva through adult stages. The RBP9 protein was detected specifically in nuclei of the nervous system after morphogenesis of the adult CNS in the mid-pupal stage. Thus, the RBP9 protein does not appear until substantially later than rbp9 transcripts are detected. The adult nervous system nuclear-limited expression pattern, the presence of RRMs, and the high similarity to a group of nervous system-specific proteins in flies and humans suggest that rbp9 belongs to a nervous system-specific RRM protein gene subfamily that may participate in the processing of RNAs involved in the development of the CNS.
Two input systems for body representations in the primate striatal matrix: experimental evidence in the squirrel monkey
Authors: Flaherty AW , Graybiel AM
Published: March 2018

The striatum is important in basal ganglia motor control and movement disorders. In this study we demonstrate the existence of two distinct sensorimotor cortical input systems to the striatum of the squirrel monkey. The first is a group of discrete zones in the extrastriosomal matrix of the putamen (“matrisomes”) that receive somatotopically organized projections from both the body map in ipsilateral primary motor cortex (MI) and maps in ipsilateral primary somatosensory cortex (SI). The second system is a group of matrisomes in largely different locations that receive somatotopically organized inputs from contralateral MI but not SI. Intracortical microstimulation and multiunit recording were used to guide deposits of multiple anterograde tracers in MI and SI. Striosome/matrix architecture was demonstrated by enkephalin immunohistochemistry. We found that inputs from regions of ipsilateral MI and SI that represented the same body parts sent projections to the same matrisomes of the ipsilateral putamen. Contralateral MI sent its strongest inputs to matrisomes that tended to interdigitate with those receiving inputs from ipsilateral SI and MI, except the contralateral MI face region, which sent projections that overlapped those from the ipsilateral MI face region. MI regions representing axial body parts (trunk and face) sent stronger representations to the contralateral putamen than did those representing distal parts (hand and foot). SI sent no contralateral projection. Thus, with the exception of the face representation, inputs from contralateral and ipsilateral body representations may alternate in the primate striatal matrix, an arrangement reminiscent of the alternating ocular dominance columns in visual cortex. Ipsilateral SI and MI and contralateral MI all innervated matrisomes intermingled with striosomes and with matrisomes not receiving sensorimotor cortical input. The patchiness of these maps is thus unlike the smoother somatotopic maps of sensorimotor cortex, and is also unlike the fractured somatotopy reported for the cerebellum.
Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms
Authors: Moskowitz MA , Nozaki K , Kraig RP
Published: March 2018

The effects of neocortical spreading depression (SD) on the expression of immunoreactive c-fos protein were examined within the superficial laminae of trigeminal nucleus caudalis (TNC), a brainstem region processing nociceptive information. KCl was microinjected into the left parietal cortex at 9 min intervals over 1 hr, and SD was detected by a shift in interstitial DC potential within adjacent frontal cortex. The stained cells in lower brainstem and upper cervical spinal cord were counted on both sides after tissues were sectioned (50 microns) and processed for c-fos protein-like immunoreactivity (LI) using a rabbit polyclonal antiserum. C-fos protein-LI was visualized in the ventrolateral TNC, chiefly in laminae I and Ilo and predominantly within spinal segment C1-2 (e.g., -1.5 to -4.5 mm from obex) ipsilaterally. SD significantly increased cell staining within ipsilateral TNC. The ratio of cells in laminae I and Ilo on the left: right sides was 1.32 +/- 0.13 after 1 M KCl, as compared to 1.06 +/- 0.05 in control animals receiving 1 M NaCl instead of KCl microinjections (p < 0.01). The ratio was reduced to an insignificant difference after chronic surgical transection of meningeal afferents and recurrent SD (1.09 +/- 0.11). Pretreatment with intravenous sumatriptan, a 5-HT1-like receptor agonist that selectively blocks meningeal C-fibers and attenuates c-fos protein-LI within TNC after noxious meningeal stimulation, also reduced the ratio to an insignificant difference (1.10 +/- 0.09). Sumatriptan or chronic surgical transection of meningeal afferents, however, did not reduce the ability of KCl microinjections to induce SD. On the other hand, combined hyperoxia and hypercapnia not only reduced the number of evoked SDs from 6.3 +/- 1.0 to 2.5 +/- 1.2 after 0.15 M KCl microinjection, but also significantly (p < 0.01) reduced associated c- fos protein-LI in TNC. These data indicate that multiple neocortical SDs activate cells within TNC. The increase in c-fos protein-LI, observed predominantly ipsilaterally, was probably mediated by SD- induced stimulation of ipsilaterally projecting unmyelinated C-fibers innervating the meninges. If true, this is the first report demonstrating that neurophysiological events within cerebral cortex can activate brainstem regions involved in the processing of nociceptive information via trigeminovascular mechanisms.
Temporal filtering properties of midbrain neurons in an electric fish: implications for the function of dendritic spines
Authors: Rose GJ , Call SJ
Published: March 2018

Electrosensory neurons in the torus semicircularis (midbrain) of the weakly electric fish Eigenmannia vary considerably in their dendritic structure and responses to modulations of the amplitude of electric organ discharges. We investigated possible relations between these properties by recording intracellularly and labeling individual neurons while modulating stimulus amplitude over rates of approximately 2–20 Hz. Morphologically distinct cell types generally differed in their responses to these stimuli. The amplitude envelope of the stimulus was nicely reflected in fluctuations of the membrane potential of heavily spined neurons. The amplitude of these stimulus-related depolarizations decreased markedly as the stimulus modulation rate was increased. For aspiny or sparsely spined neurons, however, the amplitude of stimulus- related depolarizations either increased or remained constant over this range of modulation rates. In these cells, the amplitude envelope of the stimulus was not well represented in the membrane potential. Instead, fast EPSPs were observed that varied in number over time in accordance with the amplitude envelope of the stimulus. Aspiny neurons in the tectum also coded the amplitude envelope of stimuli with poor fidelity. The amplitude of stimulus-related depolarizations, however, decreased as the rate of modulation of stimulus amplitude was increased, consistent with the notion that tectal neurons receive afferent input from the spiny toral neurons. Spiny neurons appear, therefore, to act as low-pass filters of temporal information in sensory signals. Aspiny cells, however, code high temporal frequencies. These data support the hypothesis that dendritic spines contribute to the low-pass filtering of inputs to neurons.
Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis
Authors: Schafer MK , Day R , Cullinan WE , Chretien M , Seidah NG , Watson SJ
Published: March 2018

Posttranslational processing of proproteins and prohormones is an essential step in the formation of bioactive peptides, which is of particular importance in the nervous system. Following a long search for the enzymes responsible for protein precursor cleavage, a family of Kexin/subtilisin-like convertases known as PC1, PC2, and furin have recently been characterized in mammalian species. Their presence in endocrine and neuroendocrine tissues has been demonstrated. This study examines the mRNA distribution of these convertases in the rat CNS and compares their expression with the previously characterized processing enzymes carboxypeptidase E (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) using in situ hybridization histochemistry. Furin mRNA was ubiquitously distributed and detected both in neurons and non- neuronal tissue throughout the brain with a higher abundance in ependyma, the circumventricular organs, the islands of Calleja, hippocampus, and allocortex. The cellular localization of PC1 and PC2 was exclusively neuronal with highest concentrations in known neuropeptide-rich brain regions. In general, PC2 was more widely expressed than PC1 in the CNS, although many regional variations were detected. The identification of specific combinations of convertase expression together with CPE and PAM expression in neuropeptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide precursor processing, and that these specific combinations are responsible for region-specific differences of posttranslational processing.
Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4
Authors: Tanabe Y , Nomura A , Masu M , Shigemoto R , Mizuno N , Nakanishi S
Published: March 2018

The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors. Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction. Consistent with the high degree of sequence similarity to mGluR2, mGluR3 closely resembles mGluR2 in its agonist selectivity; the potency rank order of agonists is L-glutamate > trans-1-aminocyclopentane-1,3-dicarboxylate > ibotenate > quisqualate. mGluR4 is totally different in its agonist specificity from any other member of the metabotropic receptors. This receptor potently reacts with L-2-amino-4-phosphonobutyrate (L-AP4) in a stereo- selective manner and moderately responds to L-serine-O-phosphate. mGluR4 thus corresponds well to the putative L-AP4 receptor characterized from brain preparations. Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate-putamen, and in granule cells of the hippocampal dentate gyrus. The expression pattern of mGluR4 mRNA is more restricted, and this expression is prominent in the cerebellum, olfactory bulb, and thalamus. Furthermore, the mGluR3 mRNA, unlike the other mRNAs for the metabotropic receptors, is highly expressed in glial cells throughout the brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Assembly of GABAA receptor subunits: analysis of transient single-cell expression utilizing a fluorescent substrate/marker gene technique
Authors: Angelotti TP , Uhler MD , Macdonald RL
Published: March 2018

GABAA receptor channels (GABARs) composed of varying combinations of alpha 1, beta 1, and gamma 2S subunits were transiently expressed in mammalian cell lines. The whole-cell patch-clamp recording technique was used to determine which combinations of GABAR subunits produced functional receptor channels and whether assembly of GABAR subunits into receptor channels followed a random or preferred sequence. To identify rapidly cells expressing GABARs, mammalian cell lines were cotransfected with combinations of GABAR subunit cDNAs and the Escherichia coli beta-galactosidase gene as a transfection marker. Positively transfected cells were identified by staining with the enzyme substrate fluorescein di-beta-galactopyranoside. Using this technique, we confirmed that functional alpha 1 beta 1 and alpha 1 beta 1 gamma 2S GABARs were assembled in transfected mouse L929 fibroblast cells, but surprisingly, functional alpha 1 gamma 2S and beta 1 gamma 2S GABARs were not expressed. It was determined that after transient transfection, levels of expressed receptors varied little among individual cells permitting comparison of absolute whole-cell GABA- evoked current values. Whole-cell currents recorded from cells coexpressing alpha 1 beta 1 gamma 2S subunits were three to four times larger than those recorded from cells coexpressing alpha 1 beta 1 subunits, and they were always enhanced by coapplied diazepam. The increase in whole-cell current was due in part to the larger single- channel current of the alpha 1 beta 1 gamma 2S GABARs. GABARs comprised of alpha 1 beta 1 gamma 2S subunits were formed preferentially over GABARs of alpha 1 beta 1 subunits alone, since only after substantially increasing the ratio of the beta 1 expression vector over the alpha 1 and gamma 2S subunit expression vectors were alpha 1 beta 1 GABARs formed in the presence of the gamma 2S subunit. These findings suggest that assembly of GABARs from constituent subunits did not proceed randomly to form all possible combinations, but that certain subunit combinations were preferred intermediates during the assembly process.
Phase-shifting mechanisms in the mammalian circadian system: new light on the carbachol paradox
Authors: Colwell CS , Kaufman CM , Menaker M
Published: March 2018

A variety of evidence now suggests that excitatory amino acid receptors mediate the effects of light on the circadian system of mammals. However, the ACh agonist carbachol is the only agent that has been reported to “mimic” the phase-shifting effects of light in vivo. Because the other published evidence for the involvement of ACh in light-mediated phase shifts is weak, we have referred to this situation as “the carbachol paradox.” In the present study, we found that the administration of NMDA receptor antagonists could prevent carbachol- induced phase shifts of the circadian rhythm of wheel-running activity recorded from the hamster. In addition, we found that carbachol-induced phase shifts, unlike those produced by light, are not accompanied by induction of Fos-like immunoreactivity in the suprachiasmatic nucleus (SCN). Our data are simply explained by the assumption that the intraventricular administration of carbachol causes phase shifts through a pathway distinct from that of light. Alternatively, if carbachol is acting via the light input pathway, then it must do so by a mechanism independent of Fos induction in the SCN. In either case, elucidating the mechanisms by which carbachol acts in the circadian system may provide novel insights into the cellular events by which phase shifts are generated.
The spectral sensitivity of dark- and light-adapted cat retinal ganglion cells
Authors: Guenther E , Zrenner E
Published: March 2018

The spectral sensitivity of cat retinal ganglion neurons (RGNs) was determined by means of extracellular recordings under scotopic and photopic conditions, in both receptive field center and surround. Test stimuli were presented either as square-wave single flashes or as flicker stimuli. Chromatic adaptation was achieved by a large steady monochromatic background field. In the dark-adapted state the spectral sensitivity of the majority of ganglion cells (92%) was rod mediated (peak sensitivity at 501 nm). Under photopic conditions all neurons received input from a long-wavelength-sensitive (L-cone) system with a peak sensitivity of 550 nm. Input from a short-wavelength-sensitive (S- cone) system (peak sensitivity at 450 nm), however, was found only in 15% of the ganglion cells. A small cell population (8%) located within the area centralis revealed a different receptive field organization. In these cells, spectral sensitivity in the field center peaked at 520 nm in the dark-adapted state and response threshold was about 1 log unit higher than in cells with a peak sensitivity of 501 nm. Critical flicker fusion was reached at 60–70 Hz, a frequency that usually is mediated by cones. We therefore postulate an additional input of a midspectral receptor system (M-system) other than rods in cat retinal ganglion cells. This input was found only in the receptive field center of some ganglion cells in the dark-adapted state, whereas the surround sensitivity was mediated in all cells by rod signals under scotopic and predominantly by L-cone signals under photopic conditions.
Immunocytochemical localization of a neuronal nicotinic receptor: the beta 2-subunit
Authors: Hill JA , Zoli M , Bourgeois JP , Changeux JP
Published: March 2018

We have characterized in adult rat the tissue-specific expression of the nicotinic ACh receptor (AChR) beta 2-subunit using antisera raised against fusion protein constructs. Immunohistochemical localization revealed immunoreactivity distributed throughout the neuraxis. Overall, beta 2-like immunoreactivity (beta 2-LI) correlated well with in situ localization of beta 2 transcript in neuronal cell bodies. Particularly strong labeling was detected in the thalamus, and scattered other regions, whereas relatively weak staining was observed in the hypothalamus and amygdala. At the cellular level, beta 2-LI appeared to be exclusively neuronal and concentrated predominantly in perikarya, although strongly positive dendrites (cerebral cortical pyramidal neurons, cerebellar Purkinje cells) and axon terminals (e.g., striatum) were detected. At the ultrastructural level, beta 2-LI was membrane associated, with strong staining observed in endoplasmic reticulum and cytoplasmic transport vesicles. beta 2-LI was rarely detected at synapses. The widespread distribution of beta 2 suggests it may serve as a common subunit in different AChR combinations in various brain regions. Regulation of the expression of beta 2-subunit appears to be relatively unrestrained, with an apparent excess of protein synthesized in the cytoplasm relative to that which ultimately arrives at functional targets in the plasma membrane.
Harmaline-induced impairment of Pavlovian conditioning in the rabbit
Authors: Harvey JA , Romano AG
Published: March 2018

In this study we examined the effects of harmaline on Pavlovian conditioning of the rabbit's nictitating membrane response. The acquisition of conditioned responses was determined during a single session consisting of 120 pairings of a tone-conditioned stimulus with a corneal air puff unconditioned stimulus. Harmaline severely retarded (5 mg/kg) or completely blocked (10 and 20 mg/kg) acquisition of conditioned responses. The blocked or retarded acquisition of conditioned responses could still be detected when the rabbits were tested 2 d after cessation of drug injections, suggesting that harmaline was affecting acquisition and not the motoric expression of conditioned responses. Control experiments established that harmaline (5 mg/kg) did not affect (1) baseline levels of responding, (2) the level of non-associative responding to the conditioned stimulus, (3) the amplitude or any of the temporal characteristics of the unconditioned response, (4) the development of habituation to the unconditioned stimulus, and (5) the threshold of the unconditioned stimulus for eliciting the unconditioned response. However, harmaline did produce a 12 dB increase in the intensity threshold of the conditioned stimulus for eliciting conditioned responses. We concluded that the primary effect of harmaline was to impair stimulus processing within brainstem circuits such as to reduce the excitatory properties of the conditioned stimulus, thus retarding its entry into associative learning. The results were discussed with respect to the possible role of the inferior olive in associative learning.
Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses
Authors: Perrett SP , Ruiz BP , Mauk MD
Published: March 2018

Among the many issues surrounding the involvement of the cerebellum in motor learning, the relative roles of the cerebellar cortex and cerebellar nuclei in Pavlovian conditioning have been particularly difficult to assess. While previous studies have investigated the effects of cerebellar cortex lesions on the acquisition and retention of conditioned movements, we have examined the effects of these lesions on the timing of Pavlovian eyelid responses. The rationale for this approach arises from previous studies indicating that this timing is a component of Pavlovian eyelid responses that is learned and that involves temporal discrimination. To permit within-animal comparisons, rabbits were trained to produce differently timed responses to high- and low-frequency auditory conditioned stimuli (CSs). Before the lesion the conditioned responses to both CSs were appropriately timed--each peaked near the time at which the unconditioned stimulus was presented for that CS. However, after the lesion both CSs could elicit similarly timed conditioned responses that peaked inappropriately at very short latencies. The changes in responses timing were sensitive to the size of the lesion, particularly its rostral-caudal extent. Similar results were obtained in animals trained with one CS, indicating that the disruption of response timing is not related to impaired auditory discrimination. Because response timing is learned and therefore requires synaptic plasticity, these data suggest that there are at least two sites of plasticity involved in the motor expression of Pavlovian eyelid responses. Plasticity at one site is necessary for the learned timing of conditioned responses, while plasticity at another site is revealed by the inappropriately timed responses observed following removal of the cerebellar cortex. This lesion-induced dissociation of the expression of motor responses and their learned timing supports a synthesis of competing views by suggesting that motor learning involves both the cerebellar cortex and cerebellar nuclei. We hypothesize that motor learning involves a decrease in strength of the granule cell-Purkinje cell synapses (e.g., Ito and Kano, 1982) in the cerebellar cortex and an increase in strength of the mossy fiber- cerebellar nuclei synapses (e.g., Racine et al., 1986). Finally, these data suggest that the cerebellar cortex may mediate the temporal discriminations that are necessary for the learned timing of conditioned responses.
Odorants differentially enhance phosphoinositide turnover and adenylyl cyclase in olfactory receptor neuronal cultures
Authors: Ronnett GV , Cho H , Hester LD , Wood SF , Snyder SH
Published: March 2018

Both the cAMP and the phosphoinositide (PI) second messenger systems have been implicated in olfactory signal transduction. We have developed a primary culture system of mammalian olfactory receptor neurons (ORNs; Ronnett et al., 1991a) to permit analysis of odorant- induced second messenger system activation in the intact ORN. The ability of a series of odorants to stimulate PI turnover and adenylyl cyclase was examined. All odorants stimulated both second messenger systems, although with differential potencies. Stimulation of PI turnover desensitized upon reexposure of cultures to odorant. The enhancement by single odorants of both adenylyl cyclase and PI turnover, but to varying degrees, affords a mechanism for increased specificity in olfactory signal transduction.
The behavioral repertoire of the gastric mill in the crab, Cancer pagurus: an in situ endoscopic and electrophysiological examination
Authors: Heinzel HG , Weimann JM , Marder E
Published: March 2018

Simultaneous endoscopic and electrophysiological recordings were used to observe the behavior of the gastric mill complex while recording the motor output of the stomatogastric ganglion (STG) in intact crabs. In the crab STG, many pattern-generating neurons are able to fire in several distinct rhythmic motor patterns. Specifically, many neurons can switch between firing in time with the rapid pyloric rhythm to firing in time with the slower gastric mill rhythm (Weimann et al., 1991). We now correlate behaviorally relevant movements of the gastric mill with some of the modifications of neuronal firing patterns previously characterized using in vitro STG preparations. The intracellular and extracellular recordings from the intact crab are largely indistinguishable from those obtained from in vitro preparations. For the first time, we describe the movements that result as neurons switch their activity patterns associated with activation of the gastric mill rhythm. Extracellular stimulation and intracellular depolarization of individual motor neurons is used to determine the relationship between frequency of firing and movement in behaving animals.
Effects of posterior association cortex lesions on brain potentials preceding self-initiated movements
Authors: Singh J , Knight RT
Published: March 2018

To assess the role of subregions of the posterior association cortex in movement control, we recorded movement-related potentials (MRPs) in patients who had lesions centered in the temporal-parietal junction (T- PCx; damaged areas 22, caudal 39, 40, and 42; n = 7), superior parietal cortex (ParCx; damaged areas 5, 7, rostral 39, and 40; n = 5), and posterior association cortex lesions involving both the temporal- parietal junction and the superior parietal structures (PosCx; damaged areas 7, 22, 39, 40, 41, and 42; n = 5) and in 14 age-matched normal controls. MRPs were recorded in a self-paced button-press task in which subjects performed a switch closure with the right, left, or both hands (experiment I, experiment II, and experiment III, respectively) under counter-balanced experimental conditions. Data epochs beginning 1400 msec prior to and extending to 600 msec after each motor response were recorded from scalp sites over the precentral, central, and parietal regions. Normal controls and patients with T-PCx lesions generated comparable vertex maximal, symmetrical readiness potentials (onset 1000 msec), contralaterally enhanced NS′ values (onset 500 msec), and MP values (onset 100 msec) preceding voluntary self-paced movements. Extensive lesions involving the posterior association cortex reduced MRP amplitudes. Patients with selective ParCx lesions also had marked reduction of MRPs under all experimental conditions. The MRP findings coupled with clinical and behavioral data on patients with parietal- cortex lesions indicate that the superior parietal regions are part of a neural system necessary for movement preparation.
An audio-vocal interface in echolocating horseshoe bats
Authors: Metzner W
Published: March 2018

The control of vocalization depends significantly on auditory feedback in any species of mammals. Echolocating horseshoe bats, however, provide an excellent model system to study audio-vocal (AV) interactions. These bats can precisely control the frequency of their echolocation calls by monitoring the characteristics of the returning echo; they compensate for flight-induced Doppler shifts in the echo frequency by lowering the frequency of the subsequent vocalization cells (Schnitzler, 1968; Schuller et al., 1974, 1975). It was the aim of this study to investigate the neuronal mechanisms underlying this Doppler-shift compensation (DSC) behavior. For that purpose, the neuronal activity of single units was studied during spontaneous vocalizations of the bats and compared with responses to auditory stimuli such as playback vocalizations and artificially generated acoustic stimuli. The natural echolocation situation was simulated by triggering an acoustic stimulus to the bat's own vocalization and by varying the time delay of this artificial “echo” relative to the vocalization onset. Single-unit activity was observed before, during, and/or after the bat's vocalization as well as in response to auditory stimuli. However, the activity patterns associated with vocalization differed from those triggered by auditory stimuli even when the auditory stimuli were acoustically identical to the bat's vocalization. These neurons were called AV neurons. Their distribution was restricted to an area in the paralemniscal tegmentum of the midbrain. When the natural echolocation situation was stimulated, the responses of AV neurons depended on the time delay between the onset of vocalization and the beginning of the simulated echo. This delay sensitivity disappeared completely when the act of vocalization was replaced by an auditory stimulus that mimicked acoustic self-stimulation during the emission of an echolocation call. The activity of paralemniscal neurons was correlated with all parameters of echolocation calls and echoes that are relevant in context with DSC. These results suggest a model for the regulation of vocalization frequencies by inhibitory auditory feedback.
Development of local circuits in human visual cortex
Authors: Burkhalter A , Bernardo KL , Charles V
Published: March 2018

How we see the world largely depends on the organization of neuronal circuits in visual cortex. Physiological recordings in mammals indicate that circuits develop over a period that extends well into early postnatal ages (LeVay et al., 1980; Albus and Wolf, 1984). Our understanding of how these circuits are assembled during development is still fragmentary (Katz and Callaway, 1992). Here we describe the development of local connections within visual cortex, using the fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate to trace axonal projections in post-mortem human brains. Vertical (intracolumnar) connections between layers 2/3 and 5, which link neurons representing the same point in the visual field, develop prenatally at 26–29 weeks gestation. In contrast, horizontal (intercolumnar) connections between different points in the visual field develop later. They first emerge prenatally at approximately 37 weeks gestation within layers 4B and 5. After birth (> 40 weeks gestation) the fiber density increases rapidly, showing a uniform plexus of connections at 7 weeks postnatal. The more adult-like patchiness of the projection, however, emerges after 8 weeks postnatal. Long-range horizontal connections within layer 2/3 develop after the connections within layers 4B, 5, and 6. These connections emerge after 16 weeks postnatal, long after cytochrome oxidase blobs have developed, and reach mature from sometime before 15 months of age. Unlike the patchy horizontal projections within layers 4B and 5, which seem to develop through a process of collateral elimination, long-range projections within layer 2/3 are patchy from the outset and seem to develop with greater topographical precision. The finding that intracolumnar connections develop before intercolumnar projections suggests that circuits that process local features of a visual scene develop before circuits necessary to integrate these features into a continuous and coherent neural representation of an image. In addition, the sequential development of horizontal connections within layer 4B before those within layer 2/3 suggests that circuits that may be related to the processing channel for visual motion develop in advance of those that may be more intimately related to the processing of form, color, and precise stereoscopic depth.
Pharmacology of the effects of bradykinin, serotonin, and histamine on the release of calcitonin gene-related peptide from C-fiber terminals in the rat trachea
Authors: Hua XY , Yaksh TL
Published: March 2018

The effects of inflammatory substances, bradykinin (BK), 5-HT, and histamine (HIS), on the release of calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory afferents in the rat trachea were examined ex vivo. With intralumenal perfusion, the isolated rat trachea displays low but measurable secretion of CGRP (32 +/- 4.6 fmol/10 min fraction). The addition of BK (10(-6) to 10(-4) M) to the superfusate resulted in an immediate, concentration-dependent increase in the level of CGRP (5–30-fold increase above baseline) in the perfusates, and this effect showed a concentration-dependent tachyphylaxis. [Des-Arg10]-kallidin, a B1 receptor agonist, at concentrations of up to 10(-4) M did not induce any significant increase in CGRP outflow from the rat trachea. HIS at 10(-4) M caused a modest but progressive augmentation in the release of CGRP. 5-HT at 10(- 4) M had no effect upon the resting efflux of CGRP, but at a concentration of 10(-6) M significantly enhanced the release of CGRP evoked by capsaicin (10(-6) M). Similar conditioning studies carried out with HIS and BK showed no augmentation. BK-evoked CGRP efflux was significantly inhibited by [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK (B2 antagonist) and indomethacin. While [Des-Arg9, Leu8]-BK (B1 antagonist) also caused a reduction of BK-induced release, its effect did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of met-enkephalin on GABAergic spontaneous miniature IPSPs in organotypic slice cultures of the rat hippocampus
Authors: Rekling JC
Published: March 2018

The action of met-enkephalin on GABAergic spontaneous miniature IPSPs (smIPSPs) was investigated in CA1 neurons from hippocampal slice cultures. In the presence of excitatory amino acid blockers (2,3- dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, DL-2-amino-5- phosphonovaleric acid) and TTX, a continuous high-frequency bombardment of smIPSPs was recorded. The smIPSPs were blocked by the GABAA antagonist bicuculline. The occurrence of the smIPSPs was random and their amplitude distribution was skewed toward larger smIPSPs. Met- enkephalin (10–20 microM) reversibly reduced the frequency and changed the amplitude distribution of the smIPSPs. The proportion of “large” smIPSPs was reduced, but a loss of “small” smIPSPs also contributed to the reduction in smIPSP frequency. The selective mu-receptor agonist DAGO mimicked the effect of met-enkephalin and naloxone blocked the effect of DAGO. Hyperpolarization of the neuronal membranes, produced by reducing the extracellular K+ concentration, did not reduce the frequency of the smIPSPs, nor did it block the effect of DAGO. Reduction of the extracellular concentration of Ca2+ combined with an increase in extracellular Mg2+ or the addition of Cd2+ did not reduce the smIPSP frequency, nor did it block the effect of DAGO. These results suggest that CA1 pyramidal cells of hippocampal organotypic cultures are tonically inhibited by spontaneous release of GABA, through a release mechanism that is independent of propagated sodium action potentials. Met-enkephalin and DAGO reduce the tonic inhibition by reducing the frequency of the smIPSPs, through a direct action on the presynaptic GABAergic terminals. The effect was probably not mediated by hyperpolarization of the presynaptic membrane or by modulation of presynaptic Ca2+ currents.
The number of Na+ channels in cultured chick muscle is increased by ARIA, an acetylcholine receptor-inducing activity
Authors: Corfas G , Fischbach GD
Published: March 2018

ARIA is a glycoprotein purified from chick brain on the basis of its ACh receptor-inducing activity (ARIA). In this study we present evidence that ARIA increases the number of voltage-gated sodium channels in chick muscle as well as the number of ACh receptors (AChRs). Exposure of chick myotubes to ARIA increased by twofold the number of 3H-saxitoxin binding, an effect that is comparable to the increase of AChRs assayed by 125I-alpha-bungarotoxin (125I-alpha-BTX) binding. We also documented effects of ARIA on myoblasts: the number of 125I-alpha-BTX binding sites in the mononucleated muscle cells was increased by 1.5-fold, and the peak TTX-sensitive inward currents increased by the same amount. No change was detected in the voltage dependence of channel activation, in mean channel current, or in mean channel open time. Thus, the Na+ channel is the first molecule, other than AChR subunits, whose expression has been shown to be induced by ARIA. Since sodium channels are concentrated at motor end plates, our results provide circumstantial evidence that ARIA may regulate several genes expressed at developing neuromuscular junctions. Moreover, the finding that ARIA's effects extend to mononucleated myoblasts suggests that this protein may be important during the earliest stages of muscle formation and innervation.
The neurotrophic factor concept: a reexamination
Authors: Korsching S
Published: March 2018

The neurotrophic factor concept in its basic form envisages that innervated tissues produce a signal for the innervating neurons for the selective limitation of neuronal death occurring during development (Purves, 1986; Oppenheim, 1991). This concept arose several decades ago on the basis of the observation that experimental manipulation of the amount of target tissue could modulate the size of neuronal populations. By making the survival of neurons dependent on their target, nature would provide a means to match neuron and target cell populations. NGF, discovered in the 1950s, represents the first known molecular realization of the neurotrophic factor concept. NGF was found to regulate survival, neurite growth, and neurotransmitter production of a particular neuronal type, the sympathetic neurons of the PNS. NGF produced by target cells is specifically bound and internalized by sympathetic neurons, followed by retrograde axonal transport of NGF to the cell soma, where NGF exerts its effects via the cotransported receptor molecule (Levi-Montalcini, 1987; Thoenen et al., 1987). Strictly speaking, increased neurite growth and neurotransmitter production are not trophic effects; however, I will use the term “neurotrophic” in the extended meaning of enhancing neuronal differentiation as well as neuronal survival. It was expected that these results could be generalized to a model of multiple, mutually independent, retrograde trophic messengers, which are synthesized in distinct target areas and act on restricted neuronal types (Fig. 1). This assumption leads to a conceptually simple way to arrange and maintain a variety of neuronal subsystems. One might call this a modular approach to the construction of the nervous system. The hypothesis of multiple retrograde signals has gained widespread experimental support in recent years. Originally proposed for the PNS, the model could be extended to the CNS, in which target neurons synthesize trophic factors for their afferent neurons (Ernfors et al., 1990b). In addition to NGF, a family of NGF-related molecules (now commonly called neurotrophins), which are thought to exert retrograde trophic influences (DiStefano et al., 1992), has been identified.
Visually guided reaching with the forelimb contralateral to a "blind" hemisphere: a metabolic mapping study in monkeys
Authors: Savaki HE , Kennedy C , Sokoloff L , Mishkin M
Published: March 2018

The 2–14C-deoxyglucose method was used to map local cerebral metabolic activity in monkeys performing a unimanual task requiring visually guided arm reaching and key pressing. The study was carried out with monkeys that either had intact brains or had one hemisphere deprived of visual input by unilateral optic tract section combined in some cases with forebrain commissurotomy. The metabolic mapping revealed activation of sensorimotor cortex only in the hemisphere contralateral to the moving forelimb, irrespective of whether this hemisphere was intact or visually deafferented. These results suggest that visually guided reaching with the forelimb contralateral to the “blind” hemisphere is subserved by that hemisphere's sensorimotor cortex and not by the cortex of the ipsilateral, “seeing” hemisphere. Other areas that were more active metabolically in the “blind” than in the “seeing” hemisphere included the supplementary motor, the secondary somatosensory, and certain posterior parietal cortical areas, intraparietal lateral 5 (lateral 5-ip), 7a, and intraparietal 7 (7-ip). It is suggested that the “blind” hemisphere utilizes at least two distinct pieces of information to guide forelimb movements to visual targets: (1) information about the location of the visual target derived from head and eye movements made to this target and mediated via the inferior parietal cortical areas 7a and 7-ip, and (2) information about the instantaneous upper extremity position derived from forelimb proprioceptive mechanisms and mediated via the somatosensory cortex and thereafter via the superior parietal cortical area, lateral 5-ip.
Glutamate neurons in hypothalamus regulate excitatory transmission
Authors: van den Pol AN , Trombley PQ
Published: March 2018

The hypothalamus is the crucial part of the brain that regulates homeostasis throughout the body. It governs the endocrine and autonomic nervous systems, temperature, heart rate, emotional and motivational states, reproduction, energy and water balances, and circadian rhythms. In contrast to the prevailing belief that hypothalamic neurons use peptides, neuromodulators, or other slow-acting agents as their principal neuroactive substances, we present data indicating that the primary excitatory transmitter released by medial hypothalamic neurons is glutamate. This surprising new evidence is based on three converging approaches: Immunogold cytochemistry revealed that some hypothalamic neurons and their processes in vitro contained high amounts of immunoreactive glutamate. Ca2+ digital video imaging showed that cytoplasmic Ca2+ levels of cultured neurons, elevated because of spontaneous presynaptic release of a hypothalamic transmitter, were reduced by perfusion with the selective glutamate receptor antagonists cyano-2,3-dihydroxy-7-nitroquinoxaline and 2-aminophosphonovaleric acid. Electrophysiological analysis of whole-cell patch-clamp recordings from single and pairs of monosynaptically coupled hypothalamic neurons in culture showed that virtually all spontaneous and evoked EPSPs appear to be mediated by synaptic secretion of glutamate.
Quantitative localization of AMPA/kainate and kainate glutamate receptor subunit immunoreactivity in neurochemically identified subpopulations of neurons in the prefrontal cortex of the macaque monkey
Authors: Vickers JC , Huntley GW , Edwards AM , Moran T , Rogers SW , Heinemann SF , Morrison JH
Published: March 2018

Excitatory amino acid transmission has been proposed as the principal synaptic mechanism for distribution of information through corticocortical and thalamocortical pathways. The following study utilized a double labeling paradigm, using antibodies that recognize non-NMDA ionotropic glutamate receptor subunits and other neuronal markers, to further define, quantitatively, the subclasses of neurons that contain immunoreactivity for the AMPA/kainate and kainate receptor subunits in the monkey prefrontal cortex. Double labeling with an antibody that recognizes common epitopes in AMPA/kainate subunits GluR2 and GluR3 (GluR2/3) in combination with an antibody that recognizes the kainate receptor subunits GluR5, GluR6, and GluR7 (GluR5/6/7) demonstrated that immunoreactivity for these two receptor classes was highly colocalized in a great majority of the pyramidal neurons in this region but present in only a minority of neurochemically identified subclasses of GABAergic interneurons. Furthermore, GluR2/3 immunoreactivity had principally a somatic distribution whereas GluR5/6/7 labeling was predominately found in the perikarya and/or particular dendritic domains. In contrast, intense GluR1 labeling was observed in a small subpopulation of interneurons and low GluR1 immunoreactivity was present in many other cortical neurons. These results demonstrate that there is a high degree of specificity in the distribution of AMPA/kainate and kainate receptor-class proteins to subclasses of neurons within the neocortex. A neuron's combination of excitatory amino acid receptor subunits may regulate its response to excitatory inputs and further defines the role of identified subclasses of neurons in the complex circuitry of the cerebral cortex and may also indicate the basis for the apparent cellular selectivity of excitotoxic degenerative processes.