Dynamical systems: a grammar for discussing process in ontogeny?
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Biomedical subjects
Publications and source records attributed to S R Robinson.
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Individual rat fetuses were exposed to cocaine by injection into the cisterna magna on E20 or E21 of gestation. On E20, cocaine elevated motor activity throughout the 20-min session, with activity increasing to double SAL-injected levels by the end of the session. On E21, overall activity also was elevated after cocaine, increasing four- to fivefold in the first 5 min of the session, and decreasing to twice the levels of SAL controls thereafter. Movement time series were subjected to spectral analysis to characterize cyclic motor organization. Cyclicity was evident in 67% of control and 97% of cocaine-injected fetuses. Cocaine increased the number of peaks in the movement spectrum and resulted in greater spectral density at the primary frequency of cyclic movement. Prenatal exposure to cocaine may alter patterns of cyclicity in the fetus, with consequences for the normal development of attention and behavioral state in the neonate.
The kappa opioid agonist U50,488 was administered to E21 rat fetuses via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of U50,488 promoted a threefold increase in motor activity, which was predominated by movements of caudal regions of the body (rearlimbs, body trunk, and tail). The agonist effect was reversed by IC administration of the selective kappa opioid antagonist nor-binaltorphimine. The IH injection of U50,488 had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including rearlimb, trunk, and tail movements. The IT administration of nor-binaltorphimine blocked U50,488 effects, whereas IH injection of the antagonist had little influence on fetal behavior. These findings suggest that kappa opioid receptors located in the spinal cord may play a role in the regulation of fetal motor behavior.
Intraoral infusion of milk to the rat fetus promotes opioid activity that results in reduced responsiveness in a behavioral bioassay involving perioral cutaneous stimulation. Intracisternal administration of cFP-AAF-pAB, an inhibitor of endopeptidase 24.15, prolonged the opioid activity induced by milk infusion. Treatment with the selective kappa opioid antagonist nor-binaltorphimine blocked the effect of cFP-AAF-pAB on milk-induced opioid activity, but treatment with the mu antagonist CTOP or the delta antagonist naltrindole did not. These findings imply that milk may exert its effect on fetal behavior by increasing levels of dynorphin in the fetal central nervous system.
The dopamine D1 agonist SKF-38393 and the D1 antagonist SCH-23390 were administered into the central nervous system of the E21 rat fetus via intracisternal (IC) injection. IC injection of SKF-38393 promoted a dose-dependent increase in fetal motor activity, principally including movements of the forelimbs, head, and body trunk. IC injection of SCH-23390 did not affect overall activity, but selectively suppressed forelimb, rearlimb, and head movements and promoted an increase in mouthing, licking, and facial wiping. Administration of SCH-23390 after IC injection of SKF-38393 was effective in completely reversing the behavioral effects of the D1 agonist. These findings suggest that central manipulation of dopamine D1 receptors can have direct and potent behavioral effects in the term rat fetus.
Study of behavior during development presents psychobiologists and neurobiologists with a unique set of problems that should be addressed in the design and analysis of experiments. Some of these caveats have become apparent only with the recent growth in research with subjects around the time of birth. For example, physiological regulation within the maternal-infant dyad, litter effects, the influence of context at the time of testing on performance, and dissociation of age-related change and experience, all are important experimental considerations in developmental study. Manipulation and measurement of behavioral variables in the fetus in vivo can provide one means for circumventing many of the methodological pitfalls that are associated with behavioral study of newborn subjects.
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate central nervous system. It is widely assumed that neurons using this transmitter derive it from several sources: (i) synthesizing it themselves from alpha-ketoglutarate or aspartate, (ii) synthesize it from glial-derived glutamine, or (iii) take up glutamate from the extracellular space. By use of immunocytochemistry we show that glutamate is abundant in the retinal ganglion and bipolar cells of the rabbit, but that immunoreactivity for glutamate in these neurons is reduced below immunocytochemical detection limits after the specific inhibition of glutamine synthesis in glial cells by D,L-methionine D,L-sulphoximine. GABA immunoreactivity in retinal amacrine cells was also reduced after inhibition of glutamine synthetase but the patterns and densities of immunoreactivity for taurine and glycine were unaffected. Therefore, this experimental paradigm does not induce generalized metabolic changes in neurons or glia. This study demonstrates that some glutamatergic neurons are dependent on the synthetic processes in glia for their neurotransmitter content.
Arginine8 vasopressin (AVP) was administered to rat fetuses on Embryonic Day 20 via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of AVP promoted a 4-fold increase in motor activity, including the uncommon patterns of mouthing, licking, and facial wiping. The IH injection of AVP had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including mouthing, licking, and wiping. The IT administration of a V1 antagonist blocked AVP effects, whereas IH injection potentiated AVP-induced changes in fetal behavior. The IC blockade of V1 receptors suppressed facial wiping to a chemosensory fluid (lemon) and reduced oral grasping of an artificial nipple, whereas IH injection of the V1 antagonist promoted facial wiping responses and increased grasping of the nipple. These data suggest that AVP may play a role in the development of responsiveness to stimuli encountered in the context of suckling.
Fetal rats exhibit oral grasping of an artificial nipple. The authors examined interactive effects of sensory stimuli normally encountered in the suckling environment on subsequent responses to the nipple. Embryonic Day 20 rat fetuses received an infusion of milk, lemon, or saline through a hollow artificial nipple or an intraoral cannula (producing no nipple stimulation). One minute after sensory pretreatment, behavioral responses of fetuses to an artificial nipple were recorded on videotape for frame-by-frame analysis. Preexposure to the artificial nipple decreased the number of oral grasps and facial wipes directed toward the artificial nipple but increased the duration of grasp responses. Milk uniformly reduced fetal responsiveness to the nipple. Furthermore, the artificial nipple enhanced fetal responses to perioral cutaneous stimulation, whereas milk suppressed perioral responsiveness. These data suggest that the perinatal rat's 1st experience with milk or the nipple can alter subsequent responses to suckling stimuli.
Milk promotes activity in the kappa opioid system of the rat fetus that reduces responsiveness to cutaneous stimulation. In this study, fetuses on Gestational Day 20 were presented with an artificial nipple (conditioned stimulus; CS) paired with an intraoral infusion of milk (unconditioned stimulus; US). One paired presentation of the CS and US reduced fetal responsiveness after reexposure to the CS. Selective antagonism of opioid receptors after conditioning indicated that reduced responsiveness was due to mu opioid activity. Mu and kappa opioid activity was evident after 3 paired presentations of CS and US and reexposure to milk. Kappa opioid activity during conditioning was necessary for mu involvement after reexposure to the CS or US. These experiments, which were conducted with fetal subjects that lacked suckling experience, suggest that neurochemical systems engaged during suckling may change rapidly after the newborn's initial experiences at the nipple.
Rat fetuses were exposed to cocaine, lidocaine, or saline on Gestational Day 20 or 21 to provide information about cocaine effects on behavior during prenatal development. Cocaine was administered into the cisterna magna of individual fetal subjects to restrict effects to the CNS. Behavioral effects of cocaine were compared with lidocaine to help distinguish the effects of cocaine on monoamine systems in the brain from its properties as a local anesthetic. Cocaine promoted 3-5-fold increases in fetal motor activity in the absence of explicit sensory stimulation, in contrast to the slight suppressive effects of lidocaine. Cocaine and lidocaine also reduced coordinated behavioral responses to an artificial nipple. The behavioral effects of cocaine administered into the CNS of fetal subjects suggest specific mechanisms of action on developing neural and behavioral systems in the late prenatal period.
Early experience in the context of suckling at the nipple is a crucial determinant of neurobehavioral development in mammals. In particular, milk has been recognized by developmental psychobiologists as an ecologically relevant sensory stimulus and should be viewed by clinicians as more than a source of nutrition in early human development. Gaining access to and processing milk during suckling serves as a primary focus of activity in the newborn. Because the rat fetus lacks prior exposure to milk or other suckling stimuli, it provides an excellent model system for investigating the development of milk-related responses. Fetal exposure to milk results in a cascade of behavioral, physiological and neurochemical consequences. Milk-induced activation of the endogenous opioid system plays an important role in reorganizing fetal motor activity, altering sensory responsiveness and supporting associative learning in the fetus. Subtle changes in contextual stimulation alter the ability of milk to engage different neurochemical systems. These findings suggest that the infant's first experiences with milk and other suckling stimuli may have lasting consequences for neurobehavioral development.
Intraoral infusion of milk to the rat fetus promoted changes in behavior (mouth and rearlimb movements), reduced responsiveness to perioral cutaneous stimulation, and resulted in expression of a fetal stretch response. Milk also altered the temporal organization of fetal movements over periods up to 30 min. The orosensory characteristics of milk, in the absence of ingestion, was sufficient to evoke these behavioral effects. Reduced responsiveness to a perioral stimulus had a rapid onset (< 30 s) and brief duration (< 5 min). The ability to disrupt changes in motor organization and the stretch response with an intervening stimulus also exhibited a time course after milk infusion. The findings that tactile stimulation and biomechanical manipulations of fetal movement promote rearlimb activity and facilitate expression of the stretch are consistent with a dynamic perspective of early motor development in the fetus.
Gap junctions permit the passage of ions and small molecules between cells, thereby providing a basis for direct intercellular communication. In the rabbit retina, the low molecular weight dyes Lucifer yellow and biocytin passed readily from astrocytes into adjacent astrocytes, oligodendrocytes, and Müller cells. However, the dyes rarely passed from either oligodendrocytes or Müller cells into astrocytes. Unidirectional passage of dye suggests the presence of an asymmetric barrier to the movement of molecules through heterologous gap junctions and indicates the potential for a hierarchy of command between interconnected cells.
Opioid ligands or drugs that act on dopaminergic pathways effect changes in the motor behavior of near-term rat fetuses. In this study, selective manipulation of kappa opioid and D1 DA receptors was used to investigate opioid and dopamine involvement in mediating the behavioral effects of milk infusion. Milk reduced expression of the fetal facial wiping response to a tactile probe, and this effect was blocked by the kappa antagonist nor-binaltorphimine as well as the D1 antagonist SCH-23390. Administration of either the kappa agonist U50,488 or the D1 agonist SKF-38393 mimicked the effects of milk and reduced fetal responsiveness to the probe in the absence of milk infusion. Administration of nor-binaltorphimine reversed the effects of SKF-38393 and resulted in a high incidence of the wiping response. However, administration of SCH-23390 did not reverse the low incidence of facial wiping induced by U50,488. These findings suggest that milk modulates activity at dopamine receptors, which in turn promotes activity at kappa receptors of the opioid system to bring about changes in cutaneous responsiveness in the fetal rat.
Stimuli normally encountered during suckling after birth--the nipple and milk--elicit behavioral responses from fat fetuses on E20. A series of experiments demonstrated that milk, unlike other chemosensory stimuli, consistently evoked mouthing activity during the 15 s after presentation. Unlike other perioral tactile stimuli, an artificial nipple evoked mouthing activity and an active oral grasping response during presentation. Prior exposure to milk altered fetal responsiveness to some forms of perioral tactile stimulation, but did not affect grasping of the nipple. In contrast, prior exposure to an artificial nipple increased mouthing activity in response to milk. The nipple and milk exhibit a temporally asymmetric relationship in fetal rats, which lack experience with suckling stimuli. These findings suggest that responsiveness to ecologically relevant stimuli and their temporal presentation develops before birth, and may facilitate functional behavioral responses of the newborn during the first suckling episode.
Milk promotes activity in the kappa opioid system of the rat fetus and reduced responsiveness in a behavioral bioassay of cutaneous sensitivity. In this study, E20 rat fetuses were presented with an artificial nipple (CS) and intraoral infusions of milk (US) to condition opioid activity. Paired presentations of the CS and US resulted in conditioned changes in perioral cutaneous sensitivity, which was not evident in groups exposed to the CS alone, US alone, or explicitly unpaired presentations of US and CS. Selective opioid antagonists administered between conditioning and testing revealed that reexposure to the nipple resulted in activation of the endogenous opioid system. The nipple promoted activity at mu, not kappa, opioid receptors. Conditioned opioid activity to an artificial nipple in the fetus, which lacks experience with milk or other suckling stimuli, implies that conditioned changes in the endogenous opioid system of the newborn rat may develop quickly during the first suckling episodes.
Many researchers interested in sexual orientation can be separated into two camps: The "lumpers," who try to reduce sexual classifications to as small a number of categories as possible, and the "splitters," who try to show differences among groups and individuals that make classification schemes increasingly difficult and/or intricate. We report factor analyses of the Klein Grid (a questionnaire with 21 sexual orientation items) to see how many factors emerge in two samples of strikingly different origins. In both samples, the first factor to emerge loaded substantially on all of the Klein Grid's 21 items. This factor accounted for a majority of the variance. In both samples, a second, correlated factor emerged which indexed a separation between most of the items and those having to do with social and/or emotional preferences. In both samples, a third correlated factor also emerged, but this factor differed between the two populations: one refined the social/emotional distinction and the other distinguished ideal behavior from past and current behavior. We conclude on the basis of our analysis that both the lumpers and the splitters are correct.