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PubMed2006

Nerve growth factor decreases potassium currents and alters repetitive firing in rat sympathetic neurons.

The sympathetic nervous system is an essential regulator of the cardiovascular system and interactions with target tissue regulate sympathetic neuronal properties. The heart produces nerve growth factor (NGF), which promotes sympathetic noradrenergic innervation of cardiac tissue and affects sympathetic synaptic strength. Neurotrophins, including NGF, are important modulators of synaptic plasticity and membrane electrical properties. Here we show that acute application of NGF causes a change in the repetitive firing pattern of cultured sympathetic neurons of the rat superior cervical ganglion. Neurons fire fewer action potentials in NGF, but with increased frequency, demonstrating an NGF-dependent change from a tonic to a phasic firing pattern. Additionally, NGF decreases the spike time variance, making spikes more tightly time locked to stimulus onset. NGF causes a decrease in the amplitude of both calcium-dependent and -independent potassium currents, and inhibition of calcium-dependent potassium currents using CdCl(2) reproduces some, but not all, of the firing properties induced by NGF. This study suggests that NGF release from cardiac tissue may act to modulate the repetitive firing properties of sympathetic neurons to tune their output to meet the physiological needs of the organism.

Action Potentials↗
PubMedDate not supplied

Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain: a molecular substrate for learning and memory?

The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway is an evolutionarily conserved signaling cascade involved in a plethora of physiological responses, including cell proliferation, survival, differentiation, and, in neuronal cells, synaptic plasticity. Increasing evidence now implicates this pathway in cognitive functions, such as learning and memory formation, and also in behavioral responses to addictive drugs. Although multiple intracellular substrates can be activated by ERKs, nuclear targeting of transcription factors, and thereby control of gene expression, seems to be a major event in ERK-induced neuronal adaptation. By controlling a prime burst of gene expression, ERK signaling could be critically involved in molecular adaptations that are necessary for long-term behavioral changes. Reviewed here are data providing evidence for a role of ERKs in long-term behavioral alterations, and the authors discuss molecular mechanisms that could underlie this role.

Animals↗
PubMed2025

Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study.

OBJECTIVE: To observe the effects of moxibustion at Zusanli (ST36) on rats with chronic fatigue syndrome (CFS) and to analyze the mechanisms of moxibustion through hippocampal Proteomics. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into three groups: control group (CON), model group (MOD), and moxibustion group (MOX), with 12 rats in each group. The MOD and MOX groups underwent chronic multi-factor stress stimulation for 35 d to establish the CFS model. After modeling, the rats in the MOX group received mild moxibustion at Zusanli (ST36) (bilateral) for 10 minutes daily for 28 d. During the treatment period, rats in both the MOD and MOX groups continued modeling, while the CON group was kept under normal breeding conditions. The general condition of the rats was monitored, and behaviors were assessed using the Open Field Test (OFT), Exhaustion Treadmill Test, and Morris Water Maze (MWM). Hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM) were employed to observe morphological changes in the hippocampus. Label-free Proteomics were utilized to identify differentially expressed proteins (DEPs) in the hippocampus, followed by bioinformatics analysis. The reliability of the Proteomics results was verified using Parallel Reaction Monitoring. RESULTS: A: Moxibustion at Zusanli (ST36) significantly reduced the general condition score of CFS rats, improved their behavioral performance in OFT, treadmill and MWM, and repaired the pathological and synaptic structural damage in the hippocampus.B: We identified DEPs by applying a fold change threshold of 1.2 and a significance level of P < 0.05. In the comparison between the CON and the MOD, we identified a total of 72 DEPs (31 up-regulated and 41 down-regulated) associated with the development of CFS. In the comparison between the MOX and the MOD group, we identified a total of 103 DEPs (40 up-regulated and 63 down-regulated) related to the therapeutic effects of moxibustion. Gene Ontology (GO) enrichment analysis showed that CFS and moxibustion treatment were related to multiple biological processes, molecular functions, and cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that CFS pathogenesis was linked to base excision repair, steroid biosynthesis, and systemic lupus erythematosus, Furthermore, the treatment of CFS with moxibustion was relevant to terpenoid skeleton biosynthesis.C: Compared with the two comparison groups, we identified 16 potential biomarkers, noting that moxibustion reversed the up-regulation of 14 DEPs and the down-regulation of 2 DEPs in CFS. These proteins are mainly associated with synaptic plasticity, ribosomal function, neurotransmitter secretion, glycine metabolism, and mitochondrial function. CONCLUSION: Moxibustion at Zusanli (ST36) is effective in treating CFS, the potential biomarkers identified by Proteomics confirm that the mechanisms of moxibustion involve multiple targets and pathways, which may be key to regulating the structural and functional damage in the hippocampus associated with CFS, highlighting their significant value for future research.

Animals↗
PubMed2004

HIV-resistance to viral entry inhibitors.

An increasing number of human immunodeficiency virus (HIV)-infected patients have detectable viraemia despite treatment with multiple-drug combinations or have developed resistance to all available classes of antiretroviral therapy. HIV entry has become an important pharmacological target. Enfuvirtide is the first HIV entry inhibitor to be approved for the treatment of drug-experienced patients but several other agents are progressing through preclinical and clinical trials. However, because different entry inhibitors target different parts of the entry process their combined effects could be synergistic or generate different distinct profiles of drug-resistance. The HIV envelope glycoprotein that drives HIV entry is highly variable. Its plasticity allows HIV to escape the immune system and its variability is associated with HIV tropism, fitness and replicative capacity. Thus, mutations that confer resistance to entry inhibitors will modify these parameters. Therapeutic strategies that aim at blocking virus entry may also be used to alter the natural evolution of HIV in an unprecedented way. Here, we will describe the structure and function of the envelope glycoprotein complex that constitute the basis for the emergence of resistance to HIV entry inhibitors, review those HIV entry inhibitors for which drug-resistance has been evaluated and discuss the interplay between viral resistance to inhibitors of HIV entry and the pathogenicity of HIV and AIDS.

Amino Acid Sequence↗
PubMed2002

A 13-year followup of a case of Wallenberg's syndrome: first-person account and ocular motor abnormalities.

BACKGROUND: We present a 13-year followup of a case of Wallenberg's syndrome, including a first-person account and ocular motor abnormalities. METHODS: Objective infrared eye-tracking systems were used to record horizontal and vertical eye movements binocularly under a variety of conditions. RESULTS: Fixation in the dark along the midline remained as before, with vestibular jerk nystagmus continuously present. While saccades and pursuit to a visual target also remained the same as found earlier, fixation was somewhat worse, revealing not only saccadic intrusions but also a prominent right-jerk nystagmus. DISCUSSION: The results suggest lack of additional oculomotor neural plasticity after the end of the initial 10-year test period, and furthermore reveal apparent subtle age-related changes in oculomotor responsivity.

Eye Movements↗
PubMed1996

Short-term adaptation of electrically induced saccades in monkey superior colliculus.

1. This study focuses on the neural mechanisms underlying short-term adaptation of saccadic eye movements in the rhesus monkey. Involuntary saccades of various amplitudes and directions (E-saccades) were elicited in complete darkness by electrical stimulation (< or = 50 microA) in the deeper layers of the superior colliculus (SC) at 30 different sites in two monkeys. E-saccades at a given site could be adapted by presenting a visual target at a small distance from the expected end point immediately after their occurrence. The monkeys were trained to null the ensuing error signal by making the appropriate correction saccade to the visual target in many successive trials (E-adap paradigm). By properly adjusting the location of the visual target relative to the end point of the E-saccade, the latter could be modified in amplitude as well as in direction. 2. E-saccade modifications were highly significant, always in the intended direction, and occurred only if a postsaccadic visual error signal was created. These changes were plastic and required a subsequent E-adap series with an opposite error signal to cancel them. Their time course, both during the adaptation and the readaptation period, indicated that the modification was a slow and gradual process, as has been observed earlier in classical visual adaptation experiments. 3. Postadaptation tests, assessing whether the adaptation of E-saccades was also noticeable in normal visually guided saccades (V-saccades), showed incomplete adaptation transfer that was significant in most cases. A similar result, significant in all cases, was obtained with an extended version of the E-adap paradigm in which movement planning on the basis of target selection was possible. In this case, a presaccadic visual target was presented at the expected end point of the E-saccade, which was evoked just before the monkey would make a voluntary saccade itself (VE-adap). 4. In another series of experiments, V-saccades, which were matched to the optimal saccade vector of the particular collicular site under investigation, were adapted with the classical intrasaccadic target shift paradigm (V-adap). In agreement with earlier findings, this V-adaptation showed no transfer to the E-saccades. This result was obtained even in trials in which movement planning on the basis of target selection was possible (VE-test). 5. Our experiments have shown that saccades of collicular origin can be adapted and that presaccadic target selection is not crucial for this process. Both results are nicely in line with an existing model featuring a downstream adaptive corrector with access to SC inputs. This scheme, however, does not explain why the degree of saccadic adaptation, achieved by applying any of the three adaptation paradigms (E-adap, EV-adap, or V-adap), was never equally expressed in V- and E-saccades. Arguments for extending the model by adding a cortical input from the frontal eye fields to the adaptive corrector are discussed.

Adaptation, Physiological↗
PubMed1996

Influence of sex steroids on the production of prostaglandins F2 alpha and E2 and response to oxytocin in cultured epithelial and stromal cells of the bovine endometrium.

The uterus is a primary target for sex steroid action in vivo during the estrous cycle and pregnancy. Cell cultures have been used to determine the specific function of the different cell types forming the uterus. We used endometrial cell cultures previously characterized in our laboratory to study the effect of estradiol (E) and progesterone (P4) on prostaglandin (PG) production and on regulation of the response of the cells to oxytocin (OT). The studies were performed on confluent cultures of epithelial cells grown as a monolayer either on plastic or on filter inserts to allow basal-apical polarization. As described previously, prostaglandin F2 alpha (PGF 2 alpha) production was greater (3.7-fold, p < 0.0001) than prostaglandin E2 (PGE2) production in epithelial cells, and the opposite was true in stromal cells (PGE2 9.9-fold > PGF2 alpha, p < 0.0001). In epithelial cells, the basal production of PGE2 (-61.6%, p < 0.0001) and PGF2 alpha (-51.7%, p < 0.0001) was reduced significantly by E and increased significantly by P4 (PGE2, + 30.0% [p < 0.002]; PGF2 alpha, + 22.2% [p < 0.006]). No significant effect of sex steroids on the basal production of PGs was detected in stromal cells. OT stimulated the production of PGF2 alpha (6.7-fold, p < 0.0001) and PGE2 (9.1-fold, p < 0.0001) in epithelial but not stromal cells. Treatment of the cells with E significantly (p < 0.001) increased OT-stimulated PGF2 alpha production in both the epithelial and stromal cells and that of PGE2 in epithelial cells only. The effect of steroids and OT was similar in polarized (filter) and nonpolarized (plastic) epithelial cells. Analysis of the vectorial secretion of PGs in epithelial cells grown on filter inserts revealed that PGF2 alpha is preferentially secreted in the basal (p < 0.001) compared to the apical compartment. The direction of secretion was not influenced by steroid or OT treatments. The results suggest that epithelial cells of the endometrium are a preferred target for the regulation of PG synthesis by sex steroids and OT.

Animals↗
PubMedDate not supplied

Plasticity of aged perivascular axons following exogenous NGF: analysis of catecholamines.

The present study investigated the atrophy of aged perivascular sympathetic axons and the response of these cerebrovascular neurons to the neurotrophin nerve growth factor (NGF). Using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) to quantify catecholamines and immunohistochemical methods to quantify the density of TH immunoreactive fibers, we found a significant decrease in norepinephrine (NE) and TH in aged sympathetic axons. However, following in vivo administration of exogenous neurotrophin, aged neurons exhibited a robust response to NGF that was similar to the young adult, suggesting little decline in the capability of aged neurons to utilize exogenous neurotrophin. These results suggest that the age-related atrophy of aged sympathetic axons may result primarily from reduced availability of target-derived neurotrophin rather than from intrinsic alterations of neuronal function.

Aging↗
PubMed1991

Hormonally mediated plasticity of motoneuron morphology in the adult rat spinal cord: a cholera toxin-HRP study.

The dorsolateral nucleus (DLN) and the spinal nucleus of the bulbocavernosus (SNB) of the rat lumbar spinal cord are sexually dimorphic groups of motoneurons that innervate striated perineal muscles involved in male copulatory behavior. Androgens control the development of these motoneurons and their target muscles, and continue to influence the system in adulthood. Given that several features of SNB motoneuron morphology have been shown to be androgen sensitive in adult male rats, we examined the effects of androgen manipulations on the morphology of motoneurons in the DLN in adult rats. Adult male rats were castrated and implanted with testosterone-filled or blank implants, or were subjected to a sham-castration procedure. Six weeks after treatment, motoneurons in the DLN were retrogradely labeled with cholera toxin-horseradish peroxidase (HRP) after injection into the ischiocavernosus (IC) muscle and their morphology assessed. Measures of the radial extent and coverage of the dendritic arbor of DLN motoneurons projecting to the IC (DLN-IC motoneurons) were similar across the groups, indicating comparable degrees of HRP transport. However, DLN-IC motoneurons in castrates with blank implants possessed both shorter dendritic lengths and smaller somas than those of castrates treated with testosterone. Castrates with testosterone implants had DLN-IC motoneurons that were significantly larger than those of sham castrates in dendritic length and soma area. These results suggest that motoneurons in the DLN, like those in the SNB, possess a significant degree of structural plasticity in adulthood which is influenced by androgens.

Animals↗
PubMed1990

Neuroplasticity in the olfactory system: differential effects of central and peripheral lesions of the primary olfactory pathway on the expression of B-50/GAP43 and the olfactory marker protein.

The regeneration of the olfactory neuroepithelium following olfactory bulbectomy or peripheral deafferentation was studied with mRNA probes and antibodies for B-50/GAP43 and for olfactory marker protein (OMP). Two stages in the regeneration of the olfactory epithelium could be discerned with these reagents. The first stage occurs following either peripheral deafferentation of the olfactory epithelium with Triton X-100 (TX-100) or after bulbectomy and is characterized by the formation of a large population of immature olfactory receptor neurons. These newly formed neurons express B-50/GAP43, a phosphoprotein related to neuronal growth and plasticity. During the second stage of the regeneration process the newly formed olfactory neurons mature, as evidenced by a decrease in their expression of B-50/GAP43 and an increase in the expression of OMP. This stage is only manifested if the developing neurons have access to the target olfactory bulb. Formation of a full complement of OMP-expressing neurons occurs only after peripheral lesion with TX-100. In contrast, following bulbectomy the reconstituted olfactory epithelium lacks its normal target and is compromised in its ability to recover from nerve damage, as evidenced by the presence of a large number of B-50/GAP43-expressing neurons up to 3 months after the lesion and its failure to establish a full complement of OMP-expressing neurons. These results demonstrate that the olfactory epithelium is capable of replacing its sensory neurons independently of the presence of its target, the olfactory bulb. However, the differential patterns of expression of B-50/GAP43 and OMP at long times after peripheral lesion with TX-100 or bulbectomy illustrate the profound effect the olfactory bulb has on neuronal maturation in reconstituted olfactory neuroepithelium.

Animals↗
PubMedDate not supplied

[Functional characteristics of the mature and developing brain following neuroimmunization: an analysis of the short-term plasticity of the rat hypothalamus].

In experiments on mature and developing (3-4 weeks old) rats the influence was shown of neuroimmunization with summate antigens of hippocampal or neocortical tissue cytosolic fraction on short-term plasticity of hippocampal CA3 field potentials under dentate gyrus zone stimulation. An increase of paired facilitation and frequency potentiation was revealed in pyramidal layer responses of hippocampal tissue immunized animals. In case of immunization with neocortical antigens the changes were less expressed, had mainly the opposite direction and took place in the apical dendrites zone. In young animals besides antigen spectrum depending effects of neuroimmunization an earlier manifestation (in comparison with age norm) of some focal activity definitive properties was described. The suggestions are made about different localization of hippocampal or neocortical tissue immunization "targets" with possible preferential damage of intrahippocampal systems when using this structure antigens, and also about dependence of physiological consequences on the extent of target structure ontogenetic maturity.

Animals↗
PubMed1987

T-cell surface molecules involved in the induction and expression of lymphokine-activated killing of autologous and allogeneic tumor targets.

The cellular interactions and the surface molecules involved in the generation and the expression of lymphokine-activated killer-cell (LAK) activities in vitro in blood mononuclear cells (BMN) from cancer patients and healthy individuals against autologous and allogeneic tumors were studied. The depletion of a plastic-adherent population(s) from BMN at the initiation of in vitro cultures in recombinant interleukin-2 (rIL-2) markedly interfered with the generation of LAK activities. Readdition of the same number of irradiated autologous plastic-adherent cells to the nonadherent population restored the generation of LAK. The requirement of the plastic-adherent population(s) in in vitro induction of LAK activities was observed only in autologous situations. Furthermore, selective modulations of CD3 and CD2 receptors on BMN with the appropriate monoclonal antibodies (MAb) during the induction phases of LAK responses profoundly inhibited the generation of LAK. Thus, unhindered expression of CD2 molecules and CD3 molecules were necessary for the maximum cytotoxic activation of non-antigen-driven effector cells in short-term cultures in rIL-2.

Antigen-Presenting Cells↗
PubMed2006

Ligand-based homology modeling as attractive tool to inspect GPCR structural plasticity.

G protein-coupled receptors (GPCRs) represent the largest family known of signal-transducing molecules. They convey signals for light and many extracellular regulatory molecules. GPCRs have been found to be dysfunctional/dysregulated in a growing number of human diseases and they have been estimated to be the targets of more than 40% of the drugs used in clinical medicine today. The crystal structure of rhodopsin provides the first three-dimensional GPCR information, which now supports homology modeling studies and structure-based drug design approaches. Here, we review our recent work on adenosine receptors, a family of GPCRs and, in particular, on A(3) adenosine receptor subtype antagonists. We will focus on an alternative approach to computationally explore the multi-conformational space of the antagonist-like state of the human A(3) receptor. We define ligand-based homology modeling as new approach to simulate the reorganization of the receptor induced by the ligand binding. The success of this approach is due to the synergic interaction between theory and experiment.

Adenosine A3 Receptor Antagonists↗
PubMed1986

Reformation of specific synaptic connections by regenerating sensory axons in the spinal cord of the bullfrog.

The regrowth of sensory axons into the spinal cord of juvenile bullfrogs was studied after disruption of these fibers in the dorsal root. Within 9 d after the root had been frozen, regenerating sensory axons had reached the spinal cord, as revealed by labeling with horseradish peroxidase. Growth into the spinal cord, however, was much slower. Even several months after denervation, very few fibers had reestablished any of their normal longitudinal projections within the dorsal funiculus. Eventually, however, sensory axons grew across the region and into the dorsal horn. Intracellular recordings from motoneurons revealed that these axons made functional reconnections with spinal neurons. Muscle sensory axons established direct, monosynaptic inputs to motoneurons, whereas cutaneous fibers innervated these neurons polysynaptically. Moreover, sensory afferents from a particular muscle distinguished among different classes of motoneurons, just as in normal frogs. Thus, specific synaptic pathways can be reestablished by regenerating sensory axons if they can reach their appropriate target region within the spinal cord.

Animals↗
PubMed1987

Norepinephrine in the interpeduncular nucleus of the rat: normal distribution and the effects of deafferentation.

We used correlative biochemical and histochemical methods to examine (1) the norepinephrine (NE) projection from the paired locus coeruleus (LC) to the midline interpeduncular nucleus (IPN) of the adult rat and (2) the ability of the LC to respond to denervation of their target following removal of noradrenergic afferents (6-hydroxydopamine lesions of the LC) or non-noradrenergic afferents (lesion of the paired fasciculi retroflexi(FR]. Histofluorescence revealed that the NE innervation from the two LC to the IPN is symmetric and overlapping. This projection is confined to rostral, central, and intermediate subnuclei and is absent from lateral and dorsal subnuclei. We found no evidence for homotypic collateral sprouting of undamaged LC neurons into the IPN following unilateral LC lesion. Bilateral LC lesions also did not induce sprouting by NE-containing neurons from other systems (e.g. the superior cervical ganglion or the lateral tegmental group) or from those LC neurons that survived the 6-hydroxydopamine lesion. Histofluorescence following bilateral FR lesions confirmed an earlier observation that apparent hyperinnervation of the IPN by LC afferents is elicited following removal of non-noradrenergic afferents. Measurements of the turnover rate of NE in the IPN of control animals and those that received bilateral FR lesions indicate an increased NE content and increased turnover rate of NE in the IPN of lesioned animals. Taken together these results suggest an increased number of NE terminals and an increase in the activity of tyrosine hydroxylase. No change in NE content or turnover rate was seen in the frontal cortex from these same animals. This is consistent with a target-dependent regulation of heterotypic collateral sprouting.

Animals↗
PubMed1989

Selective association of dopamine axons with their striatal target cells in vitro.

The purpose of the present study was to examine the distribution of dopamine (DA) axons after simultaneously confronting DA cells with both target cells of the corpus striatum (CS) and with non-target cells of the tectum (T). Dissociated fetal cells of rostral mesencephalic tegmentum (RMT) containing DA neurons and dissociated non-target tectal cells were exposed to wheat germ agglutinin conjugated to the fluorescent dye, rhodamine, prior to reaggregation in rotatory culture in order to distinguish these cells from non-dyed CS cells in the resulting reaggregates. After 9 days in culture, RMT-T-CS reaggregates were exposed to 10(-5)M DA and processed for DA-fluorescence histochemistry. Single reaggregates were serially sectioned and color photomicrographs prepared from each section. It was found that non-target cells (red rhodamine fluorescence) segregated from the undyed target cells, forming discrete areas containing the two cell types. DA nerve cell bodies and their processes could be distinguished by their green fluorescence. Since it is not possible to distinguish axonal from dendritic processes in a single section, the extent of neuronal dendritic arborization was estimated from reaggregates prepared from cells of the RMT and non-target T cells, in which there is no extensive proliferation of DA axons and fluorescent DA processes (presumably dendrites) are confined to the area near the cell body. Following exclusion of DA dendritic fluorescence, it was found that 85.2% of the presumed axonal fibers were present in the non-dyed areas containing striatal target cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

A critical period for the influence of peripheral targets on the central projections of developing sensory neurons.

During development, the projections that sensory neurons make within the spinal cord are influenced by the specific targets they contact in the periphery. If sensory ganglia normally supplying principally cutaneous targets are forced to grow into limb muscles, in early stage tadpoles, many sensory neurons within these ganglia innervate limb muscles and subsequently develop spinal projections appropriate for muscle spindle afferents. If the same procedure is performed with adult frogs, however, these novel projections do not form. In this study, we have determined the developmental stages at which this sensitivity to peripheral targets exists. Axons from sensory neurons in thoracic (largely cutaneous) dorsal root ganglia were re-routed into the front leg at various stages through metamorphosis, and the central spinal projections of these re-routed fibers were assessed with HRP labeling. We found that thoracic sensory axons could be made to project to limb muscles throughout development, but that the central projections of these neurons were only appropriate for spindle afferents if the fibers were re-routed before stage XVIII, shortly before metamorphic climax. Because sensory neurons can regenerate specifically into the appropriate spinal laminae even in adult frogs, these results suggest that changes in either the DRG or the arm musculature occur by stage XVII so that DRG neurons cannot respond to novel peripheral targets.

Afferent Pathways↗
PubMed2005

Role of the protomap and target-derived signals in the development of intrahemispheric connections.

Mechanisms intrinsic to the early cerebral cortex have been implicated in the establishment of cortical area identity. However, the extent to which the cortical protomap contributes to the formation of highly complex intrahemispheric connections remains obscure. Mechanisms by which postmitotic neurons establish correct corticocortical connections later in corticogenesis also remain to be elucidated. Here, we used a new transplantation method, employing donor tissue harvested from enhanced green fluorescent protein-expressing rats, to show that cortical progenitors are regionally specified for connectional potential and that this controls the development of specific intrahemispheric projections. The acquisition of connectional capacity relies on positional cues within the cortical primordium, but is independent of thalamic inputs. In addition, since cortical neurons developing in organotypic slice culture extended axons more prominently into their normal cortical target tissues than into non-target tissues, we suggest that cortical neurons respond to specific signals derived from their cortical targets.

Animals↗