bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Term GDNF Treatment Provides Long-Term Rescue of Lesioned Nigral Dopaminergic Neurons in a Rat Model of Parkinson’s Disease
Authors: Winkler Christian , Sauer Hansjörg , Lee Chong S. , Björklund Anders 
Published: April 2018

Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neuronsin vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson’s disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model.
Reconstruction of the Nigrostriatal Pathway by Simultaneous Intrastriatal and Intranigral Dopaminergic Transplants
Authors: Mendez Ivar , Sadi Damaso , Hong Murray 
Published: April 2018

The main strategy in experimental and clinical neural transplantation in Parkinson’s disease has been to place fetal nigral grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). The reason for this ectopic placement is the apparent inability of nigral grafts placed in the ventral mesencephalon (VM) of the adult host to grow axons for long distances that are capable of reaching the ipsilateral striatum and thus restoring the nigrostriatal pathway.The present study demonstrates for the first time that simultaneous dopaminergic transplants (double grafts) placed in the substantia nigra and ipsilateral striatum of rats bearing unilateral 6-hydroxydopamine lesions reconstruct the dopaminergic nigrostriatal pathway in the adult rat brain. Numerous tyrosine hydroxylase-immunoreactive axons were observed arising from the intranigral graft and growing rostrally along the internal capsule and medial forebrain bundle to reinnervate the ipsilateral striatum, which also had received a dopaminergic graft. These double grafts achieved not only greater striatal reinnervation than the standard intrastriatal graft but also a faster and more complete rotational recovery to amphetamine challenge 6 weeks after transplantation.These results suggest strongly that embryonic nigral transplants implanted in the striatum are capable of promoting growth and providing guidance to axons arising from a dopaminergic graft placed homotopically in the VM, resulting in restoration of the dopaminergic nigrostriatal projection. Reconstruction of the nigrostriatal pathway by double grafts may not only achieve substantial striatal reinnervation but may also contribute to the reestablishment of dopaminergic regulation of the nigrostriatal circuitry.
Intrinsic Variability of Ocular Dominance Column Periodicity in Normal Macaque Monkeys
Authors: Horton Jonathan C. , Hocking Davina R. 
Published: April 2018

Little is known about intrinsic variation from animal to animal in the periodicity of columnar systems within various regions of the mammalian cerebral cortex. To address this issue, complete mosaics of the ocular dominance columns were reconstructed from flat-mounts of the left and right striate cortex (V1) in six normal adult macaques (Macaca fascicularis). To identify the columns, we enucleated the right eye and subsequently processed striate cortex for cytochrome oxidase (CO) activity. Average column areas for the intact eye and the missing eye were nearly equal, confirming that monocular enucleation in adult macaques produces negligible column shrinkage. The contralateral eye’s columns occupied more territory than the ipsilateral eye’s columns, even in the central visual field representation (0° to 8°), where they predominated by 52 to 48%. The column mosaics showed remarkable variation in periodicity. The number of column pairs along the V1/V2 border ranged from 101 sets in one monkey to 154 sets in another. Average column width along the V1/V2 border ranged between 670 and 395 μm, a nearly twofold difference. The widest columns were found in the foveal representation. This high degree of innate variability should be taken into account when considering the effects of various sensory manipulations (e.g., strabismus, anisometropia), which have been reported to alter the periodicity of ocular dominance columns. We found pronounced intrinsic variation in the width and number of ocular dominance columns in a sample of sixM.fascicularis, indicating that the number of hypercolumns within a given cortical area can range widely among normal members of the same species.
The Role of Activity in the Development of Long-Range Horizontal Connections in Area 17 of the Ferret
Authors: Ruthazer Edward S. , Stryker Michael P. 
Published: April 2018

Horizontal connections in area 17 of adult cats and ferrets link cells with similar preferred orientations by a patchy network of projections extending several millimeters across the cortex. The maturation of orientation selectivity in ferret area 17 has been demonstrated previously by quantitative single-unit recording and optical imaging to begin at approximately postnatal days (P) 32–P36. We therefore made restricted injections of cholera toxin B-subunit (CTB) or CTB-gold into ferret area 17 at a series of developmental ages and statistically quantified the degree of clustering in plots of retrogradely labeled cells in tangential sections through layer III for comparison to the published values for orientation tuning at each age. At P21, horizontal connections within area 17 lacked patchiness entirely, although clear patches of labeled cells were present in extrastriate areas. By P27, significant clustering of horizontal connections within area 17 was present. A second phase of cluster refinement was observed to occur at approximately P34–P36, coinciding with the emergence of mature orientation tuning and maps. Continuous silencing of cortical action potentials by chronic tetrodotoxin infusion from P21 resulted in a spatially random distribution of retrogradely labeled cells at P34. In contrast, bilateral enucleation from P21 did not prevent the initial development of clustered horizontal connections. We conclude, based on our findings and those of others, that the anatomical specificity of long-range horizontal connections results from an activity-dependent process that initially can use spontaneous activity in the cortical and thalamic networks to establish crude periodic connections and later uses visual cues to refine these connections.
Primary Motor and Sensory Cortex Activation during Motor Performance and Motor Imagery: A Functional Magnetic Resonance Imaging Study
Authors: Porro Carlo A. , Francescato Maria Pia , Cettolo Valentina , Diamond Mathew E. , Baraldi Patrizia , Zuiani Chiara , Bazzocchi Massimo , di Prampero Pietro E. 
Published: April 2018

The intensity and spatial distribution of functional activation in the left precentral and postcentral gyri during actual motor performance (MP) and mental representation [motor imagery (MI)] of self-paced finger-to-thumb opposition movements of the dominant hand were investigated in fourteen right-handed volunteers by functional magnetic resonance imaging (fMRI) techniques. Significant increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) tasks were found in a region including the anterior bank and crown of the central sulcus, the presumed site of the primary motor cortex, during both MP (mean percentage increase, 2.1%) and MI (0.8%). In the anterior portion of the precentral gyrus and the postcentral gyrus, mean functional activity levels were also increased during both conditions (MP, 1.7 and 1.2%; MI, 0.6 and 0.4%, respectively).To locate activated foci during MI, MP, or both conditions, the time course of the signal intensities of pixels lying in the precentral or postcentral gyrus was plotted against single-step or double-step waveforms, where the steps of the waveform corresponded to different tasks. Pixels significantly (r> 0.7) activated during both MP and MI were identified in each region in the majority of subjects; percentage increases in signal intensity during MI were on average 30% as great as increases during MP. The pixels activated during both MP and MI appear to represent a large fraction of the whole population activated during MP. These results support the hypothesis that MI and MP involve overlapping neural networks in perirolandic cortical areas.
Gain of Rod to Horizontal Cell Synaptic Transfer: Relation to Glutamate Release and a Dihydropyridine-Sensitive Calcium Current
Authors: Witkovsky Paul , Schmitz Yvonne , Akopian Abram , Krizaj David , Tranchina Daniel 
Published: April 2018

We related rod to horizontal cell synaptic transfer to glutamate release by rods. Simultaneous intracellular records were obtained from dark-adapted rod–horizontal cell pairs. Steady-state synaptic gain (defined as the ratio of horizontal cell voltage to rod voltage evoked by the same light stimulus) was 3.35 ± 0.60 for dim flashes and 1.50 ± 0.03 for bright flashes. Under conditions of maintained illumination, there was a measurable increment of horizontal cell hyperpolarization for each light-induced increment of rod hyperpolarization over the full range of rod voltages.In separate experiments we studied glutamate release from an intact, light-responsive photoreceptor layer, from which inner retinal layers were removed. Steady light reduced glutamate release as a monotonic function of intensity; spectral sensitivity measures indicated that we monitored glutamate release from rods. The dependence of glutamate release on rod voltage was well fit by the activation function for a high-voltage-activated, dihydropyridine-sensitive L-type calcium current, suggesting a linear dependence of glutamate release on [Ca]iin the synaptic terminal. A simple model incorporating this assumption accounts for the steady-state gain of the rod to horizontal cell synapse.
Extracellular Serotonin in the Lateral Hypothalamic Area Is Increased during the Postejaculatory Interval and Impairs Copulation in Male Rats
Authors: Lorrain Daniel S. , Matuszewich Leslie , Friedman Ross D. , Hull Elaine M. 
Published: April 2018

Serotonin (5-HT) is generally inhibitory to masculine sexual behavior. It has been suggested that 5-HT released after ejaculation may promote the sexual quiescence of the postejaculatory interval (PEI). The following experiments were conducted to test (1) whether extracellular 5-HT increases in either the anterior lateral hypothalamic area (LHAA) or the medial preoptic area (MPOA) of male rats after ejaculation; (2) whether increasing 5-HT in these sites, by microinjecting the selective serotonin reuptake inhibitor alaproclate, could inhibit copulatory abilities; and (3) whether copulation deficits produced by alaproclate were attributable to locomotor impairments. The effects of local application of alaproclate on extracellular 5-HT levels in the LHAAand the MPOA were also tested. Extracellular serotonin was measured in all experiments usingin vivomicrodialysis.Ejaculation was correlated with enhanced 5-HT release from the LHAA; no 5-HT increases were observed before ejaculation, and levels were decreased toward basal values during a subsequent copulatory series. Elevating 5-HT in the LHAAby microinjecting alaproclate inhibited copulation by increasing the latency to mount, intromit, and ejaculate. This inhibition did not result from nonspecific locomotor impairments. In the MPOA, 5-HT release remained stable throughout copulation, and microinjecting alaproclate into this site did not significantly alter sexual behavior.These data support the large body of evidence suggesting that 5-HT is inhibitory to masculine sexual behavior. Furthermore, the LHAA, but not the MPOA, may be one site responsible for serotonergic inhibition of copulation during the PEI.
Insular Cortical Projections to Functional Regions of the Striatum Correlate with Cortical Cytoarchitectonic Organization in the Primate
Authors: Chikama Masanori , McFarland Nikolaus R. , Amaral David G. , Haber Suzanne N. 
Published: April 2018

We examined the striatal projections from different cytoarchitectonic regions of the insular cortex using anterograde and retrograde techniques. The shell and medial ventral striatum receive inputs primarily from the agranular and ventral dysgranular insula. The central ventral striatum receives inputs primarily from the dorsal agranular and dysgranular insula. Projections to the central ventral striatum originate from more posterior and dorsal insular regions than projections to the medial ventral striatum. The dorsolateral striatum receives projections primarily from the dorsal dysgranular and granular insula.These results show that cytoarchitectonically less differentiated (agranular) insular regions project to the ventromedial “limbic” part of the ventral striatum, whereas more differentiated (granular) insular regions project to the dorsolateral “sensorimotor” part of the striatum. The finding that the ventral “limbic” striatum receives inputs from less differentiated regions of the insula is consistent with the general principle that less differentiated cortical regions project primarily to the “limbic” striatum. Functionally, the ventral striatum receives insular projections primarily related to integrating feeding behavior with rewards and memory, whereas the dorsolateral striatum receives insular inputs related to the somatosensation. Information regarding food acquisition in the insula may be sent to the intermediate area of the striatum.
Prenatal Development of Layer-Specific Local Circuits in Primary Visual Cortex of the Macaque Monkey
Authors: Callaway Edward M. 
Published: April 2018

Previous studies have demonstrated that axonal arbors specific for the four main cortical layers — 2/3, 4, 5, and 6 — develop precisely from the outset using activity-independent cues. In macaque primary visual cortex (V1), layer 2/3 is subdivided into layers named 2/3A, 3B, 4A, and 4B, and layer 4 is subdivided into 4Cα and 4Cβ. Individual neurons in V1 of mature macaques have axonal arbors that are highly specific for these sublayers. We have studied the prenatal development of laminar and sublaminar specificity of local circuits in macaque V1. Two-hundred thirty-eight neurons were labeled intracellularly in living brain slices prepared from V1 of five prenatal macaque monkeys aged 100 to 145 d postconception (E100–E145). Axonal and dendritic arbors of labeled neurons were reconstructed to assess their relationships to the cortical layers. We find that developing spiny neurons in layers 2–4B and layer 5 specifically target superficial and deep layers without forming “incorrect” branches in layer 4C. Similarly, layer 6 pyramidal neurons that target layer 4C do not form “incorrect” branches in layer 5. These results indicate that specific projections to the main cortical layers develop with a high degree of selectivity, as in other species. However, the development of sublayer-specific projections was not always precise from the outset. Unlike postnatal animals, axons of some prenatal layer 4Cβ spiny neurons branch in layer 4B. At similar ages, many pyramidal neurons in the upper half of layer 6 have axonal branches in layer 4Cα as well as 4Cβ; these projections are specific for 4Cβ in more mature animals. Also, there is similar “exuberance” in axonal arbors of other layer 6 cell types. Transient projections were also observed in the subplate and to the white matter for cells from all layers, except 4Cβ. These observations indicate that at least some sublayer-specific projections emerge by elimination of exuberant axonal branches and suggest that they may use activity-dependent mechanisms to identify “correct” target layers. Such cues could be provided by laminar differences in the patterns of spontaneous prenatal activity in the retino-geniculo-cortical network.
Comparison of PlasticityIn VivoandIn Vitroin the Developing Visual Cortex of Normal and Protein Kinase A RIβ-Deficient Mice
Authors: Hensch Takao K. , Gordon Joshua A. , Brandon Eugene P. , McKnight G. Stanley , Idzerda Rejean L. , Stryker Michael P. 
Published: April 2018

Developing sensory systems are sculpted by an activity-dependent strengthening and weakening of connections. Long-term potentiation (LTP) and depression (LTD)in vitrohave been proposed to model this experience-dependent circuit refinement. We directly compared LTP and LTD inductionin vitrowith plasticityin vivoin the developing visual cortex of a mouse mutant of protein kinase A (PKA), a key enzyme implicated in the plasticity of a diverse array of systems.In mice lacking the RIβ regulatory subunit of PKA, we observed three abnormalities of synaptic plasticity in layer II/III of visual cortexin vitro. These included an absence of (1) extracellularly recorded LTP, (2) depotentiation or LTD, and (3) paired-pulse facilitation. Potentiation was induced, however, by pairing low-frequency stimulation with direct depolarization of individual mutant pyramidal cells. Together these findings suggest that the LTP defect in slices lacking PKA RIβ lies in the transmission of sufficient net excitation through the cortical circuit.Nonetheless, functional development and plasticity of visual cortical responsesin vivoafter monocular deprivation did not differ from normal. Moreover, the loss of all responsiveness to stimulation of the originally deprived eye in most cortical cells could be restored by reverse suture of eyelids during the critical period in both wild-type and mutant mice. Such an activity-dependent increase in response would seem to require a mechanism like potentiationin vivo. Thus, the RIβ isoform of PKA is not essential for ocular dominance plasticity, which can proceed despite defects in several commonin vitromodels of neural plasticity.
Vagotomy-Induced Enhancement of Mechanical Hyperalgesia in the Rat Is Sympathoadrenal-Mediated
Authors: Khasar Sachia G. , Miao Frederick J.-P. , Jänig Wilfrid , Levine Jon D. 
Published: April 2018

We have recently shown that subdiaphragmatic vagotomy enhances bradykinin-induced hyperalgesic behavior and decreases baseline paw withdrawal threshold to mechanical stimulation of the hindpaw skin in rats by a peripheral mechanism. To elucidate the underlying mechanism, we studied whether lesions of efferent neuroendocrine pathways could prevent or reverse the potentiating effect of vagotomy. In groups of sham-vagotomized or vagotomized rats, we surgically removed or denervated the adrenal medulla. Bradykinin was injected intradermally into the skin of the dorsal surface of the rat hindpaw. Threshold of paw withdrawal to mechanical stimulation of the skin was measured.Vagotomy induced a decrease in mechanical baseline paw withdrawal threshold and enhancement of bradykinin-induced mechanical hyperalgesic behavior, both of which were maintained over the 5 week testing period. Adrenal enucleation or denervation of the adrenal gland by suprarenal ganglionectomy prevented vagotomy-induced decrease in baseline paw withdrawal threshold and enhancement of bradykinin-induced hyperalgesia. In animals that had a demonstrated decrease in baseline paw withdrawal threshold and enhancement of bradykinin-induced hyperalgesia 2 weeks after vagotomy, additional denervation of the adrenal medulla significantly reversed these effects over a 3 week period.These results imply that both the decrease in baseline paw withdrawal threshold and enhancement of bradykinin-induced hyperalgesic behavior after vagotomy are dependent on a hormonal signal released from the adrenal medulla and suggest a novel mechanism of sensitization of cutaneous nociceptors.
Muscle Response to Changing Neuronal Input in the Lobster(Panulirus Interruptus)Stomatogastric System: Slow Muscle Properties Can Transform Rhythmic Input into Tonic Output
Authors: Morris Lee G. , Hooper Scott L. 
Published: April 2018

Slow, non-twitch muscles are widespread in lower vertebrates and invertebrates and are often assumed to be primarily involved in posture or slow motor patterns. However, in several preparations, including some well known invertebrate “model” preparations, slow muscles are driven by rapid, rhythmic inputs. The response of slow muscles to such inputs is little understood. We are investigating this issue with a slow stomatogastric muscle (cpv1b) driven by a relatively rapid, rhythmic neural pattern. A simple model suggests that as cycle period decreases, slow muscle contractions show increasing intercontraction temporal summation and at steady state consist of phasic contractions overlying a tonic contracture. We identify five components of these contractions: total, average, tonic, and phasic amplitudes, and percent phasic (phasic amplitude divided by total amplitude).cpv1b muscle contractions induced by spontaneous rhythmic neural inputin vitroconsist of phasic and tonic components. Nerve stimulation at varying cycle periods and constant duty cycle shows that a tonic component is always present, and at short periods the muscle transforms rhythmic input into almost completely tonic output. Varying spike frequency, spike number, and cycle period show that frequency codes total, average, and tonic amplitudes, number codes phasic amplitude, and period codes percent phasic.These data suggest that tonic contraction may be a property of slow muscles driven by rapid, rhythmic input, and in these cases it is necessary to identify the various contraction components and their neural coding. Furthermore, the parameters that code these components are interdependent, and control of slow muscle contraction is thus likely complex.
Nerve Gas-Induced Seizures: Role of Acetylcholine in the Rapid Induction of Fos and Glial Fibrillary Acidic Protein in Piriform Cortex
Authors: Zimmer Lee A. , Ennis Matthew , Wiley Ronald G. , Shipley Michael T. 
Published: April 2018

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45–60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90–120 min after soman, Fos and GFAP staining increased bilaterally in PC.In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45–60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, predominantly by the activation of muscarinic receptors.