PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “instructive signals”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

Learning neural dynamics through instructive signals.

Rapid learning is essential for flexible behavior, but its basis in the brain remains unknown. Here we introduce the PRISM plasticity rule, a unifying mechanistic model of three well-established, fast-acting synaptic plasticity rules-in hippocampus, cerebellum and mushroom body-which relies exclusively on pre-synaptic activity and an "instructive signal" from another brain area. Using a multi-region network model we show that guiding PRISM plasticity with instructive signals enables the network to quickly learn extremely flexible nonlinear dynamics underlying behaviorally relevant computations, as well as to emulate unknown external system dynamics from real-time error signals, which we demonstrate with comprehensive simulations supported by exact mathematical theory. Thus, PRISM plasticity guided by instructive signals is well-suited to rapidly learn general-purpose neural computations-in contrast to canonical Hebbian rules. Finally, we show how including this plasticity rule in artificial learning algorithms can solve long-range temporal credit assignment, a long-standing challenge in machine learning.

cerebellum↗
PubMed1991

Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements.

1. Single-cell activity was recorded from three different motor areas in the cerebral cortex: the primary motor cortex (MI), supplementary motor area (SMA), and premotor cortex (PM). 2. Three monkeys (Macaca fuscata) were trained to perform a sequential motor task in two different conditions. In one condition (visually triggered task, VT), they reached to and touched three pads placed in a front panel by following lights illuminated individually from behind the pads. In the other condition (internally guided task, IT), they had to remember a predetermined sequence and press the three pads without visual guidance. In a transitional phase between the two conditions, the animals learned to memorize the correct sequence. Auditory instruction signals (tones of different frequencies) told the animal which mode it was in. After the instruction signals, the animals waited for a visual signal that triggered the first movement. 3. Neuronal activity was analyzed during three defined periods: delay period, premovement period, and movement period. Statistical comparisons were made to detect differences between the two behavioral modes with respect to the activity in each period. 4. Most, if not all, of MI neurons exhibited similar activity during the delay, premovement, and movement periods, regardless of whether the sequential motor task was visually guided or internally determined. 5. More than one-half of the SMA neurons were preferentially or exclusively active in relation to IT during both the premovement (55%) and movement (65%) periods. In contrast, PM neurons were more active (55% and 64% during the premovement and movement periods) in VT. 6. During the instructed-delay period, a majority of SMA neurons exhibited preferential or exclusive relation to IT whereas the activity in PM neurons was observed equally in different modes. 7. Two types of neurons exhibiting properties of special interest were observed. Sequence-specific neurons (active in a particular sequence only) were more common in SMA, whereas transition-specific neurons (active only at the transitional phase) were more common in PM. 8. Although a strict functional dichotomy is not acceptable, these observations support a hypothesis that the SMA is more related to IT, whereas PM is more involved in VT. 9. Some indications pointing to a functional subdivision of PM are obtained.

Animals↗
PubMed1992

Human ameloblastoma tumors express the amelogenin gene.

Instructive signals are responsible for the regulation of the expression of gene products characteristic of many cell lineages during normal development and potentially during neoplasia. The odontogenic origin of ameloblastomas is based largely on the similarity in histologic appearance between the tumor and the developing tooth organ. A pathognomonic pattern for odontogenic tissue-specific gene expression in ameloblastomas has not been previously shown. In these studies, the gene expression parameters for human ameloblastomas have been characterized with the techniques of messenger RNA phenotyping in combination with Northern and in situ hybridization analysis of messenger RNA. The results of these studies confirm that amelogenin, a gene transcribed solely by differentiated ameloblasts, was expressed by epithelial cells from human ameloblastomas. This observation suggests that the instructive signals required for ameloblast differentiation are shared during normal development and tumorigenesis of odontogenic epithelium.

Ameloblastoma↗
PubMed1991

Development of the CD4 and CD8 lineage of T cells: instruction versus selection.

T cells bearing the alpha beta T cell receptor (TCR) can be divided into CD4+8- and CD4-8+ subsets which develop in the thymus from CD4+8+ precursors. The commitment to the CD4 and CD8 lineage depends on the binding of the alpha beta TCR to thymic major histocompatibility complex (MHC) coded class II and class I molecules, respectively. In an instructive model of lineage commitment, the binding of the alpha beta TCR, for instance to class I MHC molecules, would generate a specific signal instructing the CD4+8+ precursors to switch off the expression of the CD4 gene. In a selective model, the initial commitment, i.e. switching off the expression of either the CD4 or the CD8 gene would be a stochastic event which is then followed by a selective step rescuing only CD4+ class II and CD8+ class I specific T cells while CD4+ class I and CD8+ class II specific cells would have a very short lifespan. The selective model predicts that a CD8 transgene which is expressed in all immature and mature T cells should rescue CD4+ class I MHC specific T cells from cell death. We have performed experiments in CD8 transgenic mice which fail to support a selective model and we present data which show that the binding of the alpha beta TCR to thymic class I MHC molecules results in up-regulation of the TCR in the CD4+8+ population. Therefore, these experiments are consistent with an instructive model of lineage commitment.

Animals↗
PubMed1988

Neuronal activity in cortical motor areas related to ipsilateral, contralateral, and bilateral digit movements of the monkey.

1. Single cell activity was studied in the precentral (PCM), premotor (PM), and supplementary (SMA) motor cortex of the monkey to compare magnitudes of activity changes in relation to ipsilateral, contralateral, and bilateral digit movements. 2. Three Japanese monkeys were trained to press a small key with the right or left hand, or with both hands, in accordance with visual instruction signals given 2.6-5.4 s before a visual movement-trigger signal. Great care was taken to train the animal to use only the required part of the limb. As a result of extensive training, electromyographic (EMG) studies revealed that muscle activities before the key press were limited to the digit and hand muscles of the limb instructed to move. No overt increase or decrease in activity was detectable in the proximal limb or body muscles in relation to the key-press movements or instructions. 3. Even though the movement was thus limited to distal forelimb, distinct ipsilateral relationships were observed in 8.2% of the task-related PCM neurons. They changed their activity before ipsilateral and bilateral (but not before contralateral) key press. 4. A majority of the neurons recorded from the digit area of PCM (mostly limited to the anterior bank of the central sulcus) exhibited a contralateral relationship; namely the activity increased or decreased before the onset of the contralateral and bilateral key-press movements. In most of them, the magnitudes of the activity changes before the contralateral and bilateral movements were similar. 5. In proximal limb and trunk areas of PCM and also in the somatosensory cortex, no neurons were found to exhibit distinct relations to any of the key-press movements. 6. In both SMA and PM, a number of neurons exhibited relationships of the type never or only rarely observed in the primary motor cortex. Thirty-seven percent of SMA and 62% of PM neurons exhibited premovement activity changes before all of the key-press movements. The movement-specific type of activity was observed in 28% of SMA and 16% of PM neurons. In these neurons, the activity changes were observed in relation to only one of the right or left key-press movements or exclusively in relation to the bilateral key press. Neuronal activity resembling the majority of the PCM neurons (contralateral type) was observed in 31% of SMA and 13% of PM neurons. 7. Instruction-induced changes in activity were more often found in the secondary than in the primary motor area.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Clonal cells from embryonic retinal cell lines express qualitative electrophysiological differences.

Cells from the embryonic quail retina were immortalized with the v-mil oncogene and cloned by limiting dilution. Their phenotype was examined using the whole-cell patch clamp method. Three membrane currents, IK(IR), INa and IK, were found at different frequencies within a sample of 170 cells drawn from a large clone. Nearly all combinations of these three markers were found and the frequency of combinations showed that the markers assorted independently. Examination of clones of less than 10 cells showed that heterogeneity originates with a high probability within clones, arguing that chromosomal mutation, for example, is unlikely to account for phenotypic diversity. A possible explanation is that phenotypic differences between cells might reflect the local exchange of instructive signals. If so, then the genes for the three phenotypic markers are controlled independently.

Animals↗
PubMed1991

Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage.

Immature thymocytes, which coexpress CD4 and CD8, give rise to mature CD4+CD8- and CD4-CD8+ T cells. Only those T cells that recognize self-MHC are selected to mature, a process known as positive selection. The specificity of the T cell antigen receptor (TCR) for class I or class II MHC influences the commitment to a CD4 or CD8 lineage. This may occur by a directed mechanism or by stochastic commitment followed by a selection step that allows only CD8+, class I-specific and CD4+, class II-specific cells to survive. We have generated a mouse line expressing a CD8 transgene under the control of the T cell-specific CD2 regulatory sequences. Although constitutive CD8 expression does not affect thymic selection of CD4+ cells, selection of a class I-specific TCR in the CD8 subset is substantially improved. This outcome is consistent with a model for positive selection in which selection occurs at a developmental stage in which both CD4 and CD8 are expressed, and positive selection by class I MHC generates an instructive signal that directs differentiation to a CD8 lineage.

Animals↗
PubMed1986

Role of the monkey substantia nigra pars reticulata in orienting behaviour and visually triggered arm movements.

The role of the substantia nigra pars reticulata (SNpr) has been studied in the head-free monkey during orienting behaviour in response to visual instruction signals triggering head positioning and conditioned arm movement. During the behavioural responses we recorded the electromyographic activities of neck muscles and triceps brachii, head movement, horizontal electrooculogram and single unit activity of SNpr neurons. Activity of 38 neurons located in the medial part of SNpr were analysed during the visuo-motor task. Forty percent of these units showed a moderate decrease in tonic firing rate during postural preparation preceding the orientation toward eccentric visual signal. This decrease, unrelated with saccadic eye movements per se, was followed by a marked pause observed when the rewarded stimulus was switched on and the conditioned arm movement was executed to get the reward. These data suggest that the pause in discharge of these SNpr neurons are time locked with behaviourally relevant visual stimuli and/or appropriate motor responses.

Animals↗
PubMed1992

Early persistent activation of sperm K+ channels by the egg peptide speract.

Transduction by sperm of the instructive signal provided by the egg peptide speract involves rapid, complex changes in internal ion and cyclic nucleotide content. Here, investigations of hypotonically swollen sperm provide insight into the underlying processes and identify K+ channel activation as an initial ionic event in gamete recognition. A sustained hyperpolarization of swollen sperm is promoted by less than 2.5 pM speract and is followed (with greater than 100 pM speract) by transient repolarization and (with greater than 10 nM speract) by depolarization that is dependent on external Ca2+. Monophasic increases in pHi are produced only by greater than 25 pM speract, indicating that hyperpolarization may not directly promote alkalinization. Increased K(+)-selective (K+ greater than Rb+ greater than Cs+ greater than Na+) membrane permeability is found after all speract greater than 2.5 pM, suggesting that hyperpolarization results from persistent activation of K+ channels and that repolarization has a different ionic basis. Supporting this contention, the K+ channel blocker tetraethylammonium (20 mM) inhibits the increased K+ permeability that follows treatment of swollen sperm (and of sperm in seawater) with 2.5 pM speract. Such induced activation of K+ channels is observed in patch-clamped swollen sperm examined in the cell-attached configuration, upon application of 5-50 pM speract to the bath medium. The efficacy of externally applied speract and its potency indicate that activation is indirect and probably involves an as yet unidentified diffusible mediator whose production is promoted by speract at concentrations 0.01-0.001 times those predicted from reported estimates of the Kd for the known speract receptor.

Animals↗
PubMed1992

From pathology to physiology of the human T-lymphocyte receptor.

The recent description of a selective human CD3 gamma deficiency and other T-cell receptor (TCR)/CD3 structural and functional defects, together with previous biochemical data on the structure and interactions of the TCR/CD3 complex, may aid in elucidating the physiology of this multi-subunit membrane ensemble. CD3 gamma seemed to be required for the commitment and thymic maturation of an important fraction of T lymphocytes to the CD8 (but not CD4) lineage, perhaps by participating with the CD8 co-receptor in the instructive signal delivered through the alpha beta TCR during intrathymic positive selection by HLA class I molecules. The homologous CD3 delta component would, in contrast, be necessary for the selection of CD4 lymphocytes by HLA class II molecules. The interaction of CD4 and CD8 with the TCR/CD3 complex during antigen recognition may thus be asymmetrical, taking place through CD3 delta and gamma, respectively. Also, the existence of in vivo functional TCR/CD3 hemireceptors (lacking either CD3 gamma or CD3 delta) is suggested, and defects in their relative amount on the T-cell surface may disrupt unresponsiveness to self antigens and generate autoimmunity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Sequential expression and differential function of multiple enamel proteins during fetal, neonatal, and early postnatal stages of mouse molar organogenesis.

We have established the time and position of expression for multiple enamel proteins during the development of the mouse molar tooth organ. Using high-resolution two-dimensional gel electrophoresis coupled with immunoblotting and immunocytochemistry, a 46-kDa enamel protein (pI, 5.5) was detected during late cap stage (18-days gestation, E18d) within differentiation-zone-II inner enamel epithelia associated with an intact basal lamina. At E19d a second enamel polypeptide of 72 kDa (pI, 5.8) was identified at the time and position of initial biomineralization in differentiation zone V. At 20 days, differentiation-zone-VI ameloblasts without basal lamina (late bell stage) expressed 46- and 72-kDa enamel proteins and, in addition, expressed a relatively more basic 26-kDa enamel protein (pI, 6.5-6.7); detected after initial formation of calcium hydroxyapatite crystals. Antibodies raised against chemically synthesized enamel peptides cross-reacted with both the 72-kDa and 26-kDa polypeptides, but did not cross-react with the 46-kDa enamel polypeptide. The sequential expression of multiple enamel proteins suggests several functions: (a) the anionic enamel proteins may provide an instructive template for calcium hydroxyapatite crystal formation; (b) the more neutral proteins possibly serve to regulate size, shape and rates of enamel crystal formation. We suggest that initial expression of enamel gene products during mouse tooth development possibly recapitulates ancestral features of amelogenesis documented in prereptilian vertebrates. These results imply that multiple instructive signals may be responsible for mammalian enamel protein induction and that the sequential expression of a family of enamel proteins reflects the evolutionary acquisition of a more complex genetic program for amelogenesis.

Animals↗
PubMed1992

T cell development and selection in the thymus.

T cell receptor (TCR) transgenic mice have been useful models to study the selection of lymphocytes during T cell development. They also have raised new questions with regard to allelic exclusion of T cell receptor genes and mechanisms determining the CD4/CD8 phenotype of mature T cells. Our data indicate that exclusion of beta and alpha TCR alleles occurs by different mechanisms: the expression of beta TCR genes as cell surface proteins in the absence of alpha, gamma or delta TCR chains apparently suppresses effectively further rearrangement of the beta TCR locus in spite of the presence of an active recombination machinery in these cells. In contrast an alpha TCR surface protein has little effect on further alpha TCR rearrangement which only ceases after positive selection of alpha beta T cells. This enables a developing T cell to test various alpha TCR chains with one beta TCR chain in the formation of a selectable receptor. Further data support the concept that different signals instruct developing T cells to either become CD4+8- helper or CD4-8+ killer cells: CD4+8+ cells with high levels of a class I MHC specific TCR were shown to result exclusively from positive selection and developed in vitro in the absence of selecting ligands in CD4-8+ but not CD4+8- T cells.

Animals↗
PubMed1991

Principal neurons and small intensely fluorescent (SIF) cells in the rat superior cervical ganglion have distinct developmental histories.

Sympathetic ganglia contain 2 adrenergic derivatives of the neural crest: principal neurons and small, intensely fluorescent (SIF) cells. The developmental mechanisms responsible for the generation of these 2 cell classes in vivo are not well understood. To examine the possible developmental and lineage relationships between differentiating principal neurons and SIF cells, a fluorescence microscopic study utilizing antibodies against tyrosine hydroxylase (TH) and catecholamine histofluorescence has been combined with the ultrastructural examination of embryonic and postnatal rat superior cervical ganglia (SCG). On embryonic day 12.5, before neuroblasts had become postmitotic, the cells in the SCG possessed intense TH immunoreactivity and had weak to bright catecholamine histofluorescence, but no cells displayed the fine structure of mature SIF cells or neurons. At embryonic days 16.5 and 18.5, postmitotic principal neurons expressed more moderate levels of TH and catecholamines characteristic of the late embryonic and postnatal SCG. By contrast, a small number of cells containing intense TH or catecholamine fluorescence were present in embryonic day 16.5 and older ganglia. Almost all of the intensely fluorescent cells observed were found apposed to capillaries within the ganglion. These embryonic intensely fluorescent cells were larger than SIF cells seen postnatally. Ultrastructural examination of developing ganglia confirmed that cells containing numerous large, dense-cored vesicles (LDCVs) were a prominent feature of ganglia that also contained intensely fluorescent cells. In addition, some embryonic cells containing LDCVs were mitotic. From these and other studies, it seems likely that during development, neuron precursors, in response to differentiation factors such as fibroblast growth factor (FGF) and/or NGF, acquire overt neuronal traits and become postmitotic. Subsequently, cells resembling mature SIF cells appear next to blood vessels, where they may have received other instructional signals such as glucocorticoids. This developmental scheme suggests that the differentiation of principal neurons and SIF cells is independently regulated, and that the ability of SIF cells to convert into principal neurons observed in vitro cannot account for the generation of neurons in vivo.

Animals↗
PubMed1985

Contrasting neuronal activity in supplementary and precentral motor cortex of monkeys. I. Responses to instructions determining motor responses to forthcoming signals of different modalities.

The present report contrasts neuronal activity in two motor cortical fields after instructions that determine which of two sensory signals will trigger a movement and which will not. The goal of the study was to determine possible differential roles of the two cortical fields in the process of preparing to move in response to one external cue and to ignore another. Single-cell recordings were made from the supplementary motor area (SMA) and the precentral motor area (PCM) of monkeys trained to perform key-press movements in two different modes. In the auditory mode, an instruction signal warned the animal to prepare to start the movement promptly in response to a forthcoming 1,000-Hz tone burst (trigger signal), but to remain motionless if the signal was vibrotactile (nontrigger signal). In the tactile mode, the trigger and nontrigger signals were reversed: a different instruction signal warned the animal to prepare to perform the key-press movement in response to the vibrotactile cue, but to withhold it in response to the 1,000-Hz tone. The instruction signals were auditory tones of 300 Hz for the auditory mode and 100 Hz for the tactile mode. Out of 259 task-related SMA neurons, 128 (49%) responded to instructions. Three types of instruction responses were observed: 1) 95 neurons showed continuous instruction-induced activity changes lasting until the occurrence of the movement-triggering signal, regardless of whether an intervening nontrigger signal occurred. 2) 24 neurons showed increased activity until the occurrence of the nontriggering signal, after which the activity subsided. When there was no nontrigger signal, the activity increased during a period when the nontrigger signal might have been given. 3) Nine neurons responded with a transient, short-latency discharge after the instruction. The responses of SMA neurons to two instructions were often different. Forty-four SMA neurons exhibited a selective response to only one of the two instructions. In 43 neurons the response was differential, with the magnitude of activity increase or decrease being at least three times greater after one instruction than the other. In the remaining 41 neurons the response was nondifferential. Out of 112 task-related PCM neurons, 25 (22%) responded to the instructions. In the majority of them (21 neurons), the instruction response was nondifferential.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis.

A major unsolved problem in developmental biology is to determine when and how time- and position-restricted instructions are signaled and received during secondary embryonic inductions such as branching morphogenesis. The mouse embryonic lung rudiment was used to test the hypothesis that endogenous peptide growth factors, specifically epidermal growth factor (EGF), serve as instructive epigenetic signals for morphogenesis. The presence of EGF precursor mRNA transcripts was detected using the reverse-transcriptase-coupled polymerase chain reaction both in E11-E17-day mouse embryo lung tissues in vivo and in E11-day lung cultured for up to 7 days in vitro under chemically defined, serum-free conditions. Immunolocalization identified a position-restricted distribution of EGF in and around the primitive airways both during in vivo lung morphogenesis and in culture. EGF receptors (EGFR) coimmunolocalized with EGF in the primitive airways. Addition of exogenous EGF to lungs in culture resulted in significant concentration-dependent stimulation of branching morphogenesis, DNA, RNA, and protein content, and in [3H]thymidine incorporation into DNA. Conversely, the addition of tyrphostin (specific EGF receptor kinase antagonist) to lungs in culture resulted in concentration-dependent inhibition of branching morphogenesis, DNA, RNA, and protein content, and in [3H]thymidine incorporation into DNA without apparent cytotoxicity. The inhibition of the EGF signal by tyrphostin was confirmed by immunoprecipitation of tyrosine phosphoproteins. We conclude that early mouse embryo lungs express EGF transcripts and corresponding EGF peptides in a specific position-restricted distribution which coimmunolocalizes with EGFR in the primitive airways, while stimulatory and inhibitory studies indicate a functional role for the transduced EGF signal in the epigenetic regulation of lung branching morphogenesis. We speculate that the peptide growth factor EGF serves a function in secondary embryonic morphogenetic inductions, which may be modulated by interaction with other growth factors.

Animals↗
PubMed1991

Consistent arterial abnormalities associated with a variety of congenital malformations of the human lower limb.

A number of seemingly unrelated congenital deformities of the lower limb have been presented which include clubfoot, fibular deficiency, tibial aplasia, and diplopodia. Although the bony morphology in these limbs is quite different, they all share a strikingly similar arterial pattern, that being deficiency or absence of the anterior tibial artery, and of its derivative, the dorsal pedis artery. Since all of these diverse conditions share a similar aberrant arterial pattern, we suspect that the arterial changes are important in the pathogenesis of those conditions. Study of the soft tissue anatomy of these specimens suggests that the etiologic teratogenic event occurred early in embryonic development. In those limbs that contain the remnant of a missing structure, it is concluded that injury occurred after the mesenchyme was instructed to form that structure. These are termed "post-specification" defects. In those circumstances where limb duplication occurs, the injury affected the signal before instruction of mesenchyme to develop into a specific structure was completed and these abnormalities are termed "pre-specification" malformations. The musculotendenous and neurologic abnormalities seem to be reactive to the pre-existing bony pattern.

Angiography↗
PubMed1979

Patient-initiated transtelephone transmission of electrocardiographic signals in the diagnosis of arrhythmias.

Thirty-one patients who had complained of recurrent palpitations were given transtelephone transmitters of electrocardiographic signals and instructed to use the transmitters while they were having symptoms. From the transcribed electrocardiograms sinus tachycardia was documented in 12 patients, paroxysmal atrial tachycardia in 7, atrial fibrillation in 4, atrial flutter in 3, frequent ventricular premature beats in 4 and ventricular tachycardia in 1. Patient-initiated transtelephone transmission of electrocardiographic signals was found to be an effective means of documenting the nature of symptomatic paroxysmal tachycardia.

Adolescent↗