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Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency.

Thyroid hormones are critical for the development and maturation of the central nervous system. Although somatic and neurological effects are well documented following severe thyroid hormone deprivation, much less is known of the functional consequences of moderate levels of hormone insufficiency. We have previously demonstrated that severe thyroid hormone reductions in the postnatal period are associated with impairments in synaptic transmission in the dentate gyrus. The present study was performed to examine the dose-response relationships of moderate levels of hormone disruption on synaptic function in the dentate gyrus in an in vivo preparation and to determine the effects on spatial learning. Pre- and postnatal thyroid hormone insufficiency was induced by administration of 3 or 10 ppm propylthiouracil (PTU) to pregnant and lactating dams via the drinking water from gestation day (GD) 6 until postnatal day (PN) 30. This regimen produced a 47% and 65% reduction in serum T4, in the dams of the low and high-dose groups, respectively. At the time of testing of adult offspring, hormone status had returned to control levels. In littermates, field potentials evoked in the dentate gyrus in response to stimulation of the perforant path were assessed under urethane anesthesia. The data reveal dose-dependent reductions in synaptic transmission and impairments in long-term potentiation (LTP) of the EPSP component of the compound field potential. In contrast, LTP of the population spike measure was paradoxically enhanced. Spatial learning in the Morris water maze was profoundly impaired in high-dose animals. Although the majority of subjects in the low-dose group eventually acquired the task, their acquisition rate lagged behind control values. Reversal learning was assessed in all animals reaching criterion performance and found to be impaired in PTU-exposed animals relative to controls. These data support previous findings in area CA1 in vitro, extend observations associated with dentate gyrus synaptic function to a lower dose range, and provide correlative evidence of behavioral disruption in a hippocampal-dependent learning task following developmental thyroid hormone insufficiency.

Age Factors↗

Effect of spatial frequency of stimulus on focal macular ERGs in monkeys : fmacERG dependence on the spatial-frequency.

PURPOSE: To determine the effect of the spatial frequency of a small grating stimulus centered on the macula on the focal macular ERGs (fmacERGs) of monkeys. METHODS: fmacERGs were recorded from eight eyes of four adult monkeys (Macaca fuscata). The spatial frequency of the stimulus was changed from 0.25 to 8 cycles/degree. The luminance of the light bars was 10 cd/m(2), and the contrast was 95%. The stimulus was flashed on and off with an on duration of 100 ms and an off duration of 150 ms (4 Hz). The stimulus was centered on the fovea and subtended 12.7 degrees at the cornea. The luminance of the steady light-adapting background was 3.5 cd/m(2). The location of the stimulus on the retina was monitored throughout the recordings. The effects of the spatial frequency of the stimulus on the amplitudes and implicit times of the a-waves, b-waves, and oscillatory potentials (OPs) were determined. fmacERGs were also recorded following intravitreal tetrodotoxin (TTX). RESULTS: The amplitudes of the a- and b-waves did not change with changes in the spatial frequency of the stimulus. The OPs, on the other hand, responded best to the lowest spatial frequency, and the OPs after the first two were attenuated at intermediate and higher frequencies (Wilcoxon signed-rank test: P < 0.05). TTX reduced all OP wavelets in monkeys. CONCLUSIONS: The OPs of the photopic macular ERGs are affected by the spatial frequency of the stimulus and are reduced by TTX, consistent with their being generated by inner retinal neurons.

Adaptation, Ocular↗

Spatial and temporal dependencies of cross-orientation suppression in human vision.

A well-known property of orientation-tuned neurons in the visual cortex is that they are suppressed by the superposition of an orthogonal mask. This phenomenon has been explained in terms of physiological constraints (synaptic depression), engineering solutions for components with poor dynamic range (contrast normalization) and fundamental coding strategies for natural images (redundancy reduction). A common but often tacit assumption is that the suppressive process is equally potent at different spatial and temporal scales of analysis. To determine whether it is so, we measured psychophysical cross-orientation masking (XOM) functions for flickering horizontal Gabor stimuli over wide ranges of spatio-temporal frequency and contrast. We found that orthogonal masks raised contrast detection thresholds substantially at low spatial frequencies and high temporal frequencies (high speeds), and that small and unexpected levels of facilitation were evident elsewhere. The data were well fit by a functional model of contrast gain control, where (i) the weight of suppression increased with the ratio of temporal to spatial frequency and (ii) the weight of facilitatory modulation was the same for all conditions, but outcompeted by suppression at higher contrasts. These results (i) provide new constraints for models of primary visual cortex, (ii) associate XOM and facilitation with the transient magno- and sustained parvostreams, respectively, and (iii) reconcile earlier conflicting psychophysical reports on XOM.

Adult↗

The spatial limit for motion detection in noise depends on element size, not on spatial frequency.

When a random spatial noise pattern is displaced for a short distance it seems to move coherently, but when the displacement exceeds a certain value, the direction of motion cannot be clearly perceived. We measured the displacement limit (Dmax) for a two-frame sequence and found that it depended on the size of the elements comprising the random pattern, even when low spatial frequencies were removed from the pattern by spatial band-pass filtering. Dmax depended strongly on contrast for the filtered patterns, but less so for the unaltered patterns. The data support a model for low level motion detection in which the maximum motion displacement that can be detected is determined by the mean separation of pattern elements, following a stage of low-pass spatial filtering, and in which the upper spatial displacement depends upon the pattern statistics, not upon the size of detectors in the visual system.

Filtration↗

Effects of irrelevant spatial S-R compatibility depend on stimulus complexity.

Choice-reaction time is known to depend on the spatial correspondence of stimulus and response, even if the stimulus location is irrelevant to the task (Simon effect). An experiment investigated whether this effect depends on stimulus complexity--i.e., on whether properties of the stimulus render stimulus discrimination easy or difficult. It was hypothesized that high demands on discrimination slow down the processing of stimulus identity in relation to location, so that the facilitating or conflicting location code has more time to decay, thus losing impact on response selection. In fact, the results revealed an effect or irrelevant spatial S-R correspondence with easy, but not with difficult, stimulus discrimination. This finding resolves an apparent contradiction between the results of several previous experiments on the Simon effect.

Adolescent↗

Attentional distraction of CNV depending on the spatial focus.

To investigate the distraction of spatial attention to the task-irrelevant visual stimuli, contingent negative variation (CNV) was measured by using a forewarned reaction time task in 20 healthy subjects. The lasting emission of light, irrelevant to the CNV task, at each perimetric angle of 15 degrees, 30 degrees or 45 degrees to the fixated point was presented to the subjects. The amplitude of early CNV was small only under the light-emission at the angle of 30 degrees. Our results indicate that attention is distracted even by the lasting, task-irrelevant stimuli and that distraction is dependent on the focusing function of attention.

Adolescent↗

Methane emissions from a constructed wetland treating wastewater--seasonal and spatial distribution and dependence on edaphic factors.

Constructed wetlands for wastewater treatment have many advantages. They can be used for several purposes, for example, to reduce levels of organic matter and nutrients, and to retain toxic metals. However, most wetlands are inherently net sources of gaseous compounds like methane and nitrous oxide, which are of environmental concern due to their rapid current accumulation in the atmosphere and their potent global warming capacity. In order to determine the flux of methane from a constructed wetland a study was conducted over two growth seasons on a pilot scale wetland constructed to reduce nutrient levels in secondary treated wastewater. The emissions for the spring to autumn period averaged 141 mg CH(4)m(-2)d(-1) (S.D.=187), ranging from consumption of 375 mg CH(4)m(-2)d(-1) to emissions of 1739 mg CH(4)m(-2)d(-1). The spatial and temporal variations were large, but could be accounted for by measured environmental factors. Among these factors, sediment and water temperatures were significant in all cases and independent of the scale of analysis (r(2) up to 0.88).

Ecosystem↗

Spatial and spectral dependence of the auditory periphery in the northern leopard frog.

We investigated directionalities of eardrum vibration and auditory nerve response in anesthetized northern leopard frogs (Rana pipiens pipiens). Simultaneous measures of eardrum velocities and firing rates from 282 auditory nerve fibers were obtained in response to free-field sounds from eight directions in the horizontal plane. Sound pressure at the external surface of the ipsilateral eardrum was kept constant for each presentation direction (+/- 0.5 dB). Significant effects of sound direction on eardrum velocity were shown in 90% of the cases. Maximum or minimum eardrum velocity was observed more often when sounds were presented from the lateral and posterior fields, or from the anterior and contralateral fields, respectively. Firing rates of 38% of the fibers were significantly affected by sound direction and maximum or minimum firing rate was observed more frequently when sounds were delivered from the lateral fields, or from the anterior and contralateral fields, respectively. Directionality patterns of eardrum velocity and nerve firing also vary with sound frequency. Statistically significant correlation between eardrum velocity and nerve fiber firing rate was demonstrated in only 45% of the fibers, suggesting that sound transmission to the inner ear through extratympanic pathways plays a non-trivial role in the genesis of directionality of auditory nerve responses.

Animals↗

Reduced hippocampal CA1 Ca(2+)-induced long-term potentiation is associated with age-dependent impairment of spatial learning.

Expression of Ca(2+)-induced CA1 long-term potentiation (LTP) was analysed in hippocampal slices obtained from (1) 3-month-old and (2) 18-20-month-old Sprague-Dawley rats selected for their performances in the Morris water maze task. In all slices, a transient (10 min) increase of extracellular Ca2+ concentration (4 mM) caused a long-lasting enhancement of potentials evoked by electrical stimulation of radiatum fibers. However, a significant difference was found in the degree of potentiation among groups. In particular, increases of the CA1 response amplitudes were significantly lower in old rats impaired in spatial learning than in young at 30 (P < 0.05), 60, 90 and 120 min (P < 0.01) after restoring the normal Ca2+ concentration. On the contrary, no differences were observed between young animals and the old ones with good performances in spatial learning. The data suggest that amplitude of CA1 Ca(2+)-induced LTP in old rats is related to spatial learning abilities.

Aging↗

Visual hemispheric asymmetries depend on which spatial frequencies are task relevant.

Observers classified sine-wave and square-wave gratings on the basis of fundamental frequency (Are the bars wide or narrow?) or on the basis of higher harmonic frequencies (Are the bars sharp or fuzzy?). Stimuli were presented in either the left (LVF) or right (RVF) visual field. When the classification was made on the basis of the fundamental frequencies (1 or 3 c/deg), there was a LVF/right hemisphere advantage. However, when the classification was on the basis of a sharp/fuzzy distinction which involved searching for the higher harmonic frequencies, then a RVF/left hemisphere advantage was found.

Adult↗

Serotonin-dependent maintenance of spatial performance and electroencephalography activation after cholinergic blockade: effects of serotonergic receptor antagonists.

The interaction between acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5-HT) in the control of behavior such as spatial navigation has received considerable attention over the last years. Previous research indicates that while a selective reduction in cholinergic transmission often produces only mild impairments in spatial and other behavioral tests, additional serotonergic blockade results in the appearance of severe behavioral deficits. Consequently, it has been argued that 5-HT plays a role in the maintenance of behavioral capacities in the face of reduced cholinergic transmission. Here, we examined the effects of 5-HT depletion and receptor blockade, alone and in combination with cholinergic-muscarinic antagonism, on spatial navigation of rats in the Morris water maze. Further, electroencephalographic (EEG) recordings were taken to test the hypothesis that a loss of neocortical activation is related to the behavioral deficits apparent after cholinergic-serotonergic blockade. The muscarinic antagonist, scopolamine (1 mg/kg) produced a moderate impairment in navigational performance. The 5-HT depletor, p-chlorophenylalanine (PCPA; 500 mg kg(-1) day(-1)x2) did not impair performance when given alone but strongly potentiated the scopolamine-induced deficit and completely blocked the acquisition of an escape response in the water maze. This effect was mimicked by the non-selective serotonin(1-2) receptor antagonist, methiothepin (0.3 mg/kg), but not by the selective serotonin(1A) antagonist, WAY 100635 (0.1-0.5 mg/kg) or the serotonin(2) antagonist, ketanserin (2-4 mg/kg). None of the 5-HT antagonists impaired performance when given alone. Electrocorticographic recordings in rats treated with scopolamine and serotonergic receptor antagonists showed that during behavioral immobility, scopolamine (1 mg/kg) increased spectral power in all frequency bands between 0.5 and 20 Hz without significantly affecting cortical activity during movement. None of the 5-HT antagonists affected cortical activity when given alone. However, methiothepin, at the same dose that produced behavioral impairments, increased spectral power between 0.5 and 4 Hz and between 8 and 12 Hz during movement when co-administered with scopolamine. The results suggest that a concurrent blockade of multiple 5-HT receptors, but not selective blockade of serotonin(1A) or serotonin(2) receptors alone, mimics the ability of global 5-HT depletion to abolish behavioral capacities that are resistant to muscarinic receptor blockade. The behavioral deficits observed here are accompanied by a reduction in neocortical activation, suggesting that disturbances of processing in cortical networks can contribute to the behavioral disorganization apparent after cholinergic and serotonergic blockade. A focus on concurrent serotonergic-cholinergic deficits may provide a useful framework for the development of novel pharmacological treatments to counteract the behavioral disorganization and loss of EEG activation present in senile dementia and Alzheimer's disease.

Acetylcholine↗

Contrast dependency of foveal spatial functions: orientation, vernier, separation, blur and displacement discrimination and the tilt and Poggendorff illusions.

To examine the effect of reducing luminance contrast in human foveal vision, discrimination thresholds were measured in four tasks and also a numerical measure of two visual illusions were obtained by a nulling technique. The patterns used for all tasks were made very similar to facilitate comparison between them--all featured luminance step edges whose contrast could be varied from near unity down to the detection threshold. Orientation, vernier and blur discrimination thresholds rise on average 5-6-fold when the contrast is reduced from near unity to a Michelson value of 0.03. Jump displacement thresholds are somewhat more robust to contrast reduction, and the curve of separation discrimination versus contrast is much shallower, rising by a factor of about 2. The magnitude of the Poggendorff and tilt illusions changes very little until the inducing contours are barely detectable.

Adult↗

The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation.

Evolution of the human heart has incorporated a variety of successful strategies for motion used throughout the animal kingdom. One such strategy is to add the efficiency of torsion to compression so that blood is wrung, as well as pumped, out of the heart. Models of cardiac torsion have assumed uniform contractile properties of muscle fibers throughout the heart. Here, we show how a spatial gradient of myosin light chain phosphorylation across the heart facilitates torsion by inversely altering tension production and the stretch activation response. To demonstrate the importance of cardiac light chain phosphorylation, we cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy.

Animals↗

Social isolation stress during the third week of life has age-dependent effects on spatial learning in rats.

Despite extensive research on the relationship between acute stress and hippocampal function in adults, little is known about the short- and long-term effects of prolonged juvenile stress on learning, memory, and other hippocampal functions. This experiment investigated whether spatial learning would be altered in juvenile and adult rats previously exposed to a chronic stressor: 6 h of social isolation (SI) daily at 15-21 days of age. SI was found to increase circulating plasma levels of corticosterone (CORT) and allopregnanolone (3-alpha,5-alpha-pregnan-20-one; 3,5-THP) at 1 h after separation on the fourth day, indicating that the isolation was an effective stressor. When tested as juveniles (post-natal (PN) 22-24), spatial learning was impaired on the Morris water maze in the previously isolated subjects compared to non-isolated controls. However, when tested as adults (PN 92-94), subjects previously exposed to SI during the third week of life demonstrated more rapid learning of the task than controls. These results are discussed in light of research on the effects of CORT on the developing hippocampus.

Aging↗

Age-dependent deficits in spatial memory are related to impaired hippocampal kindling.

Fischer 344 rats, 3 and 26 months of age, were first tested in an eight-arm spatial maze to assess memory function behaviorally. The same animals were then subjected to hippocampal kindling to examine alterations in neuronal plasticity as a function of aging. The results indicated that spatial memory was poorer and hippocampal kindling slower in aged rats than in young ones. Furthermore, there was a striking positive relation between performance in the eight-arm spatial maze and speed of kindling. This finding suggests that age-related deficits in spatial memory and hippocampal kindling reflect decreased efficacy of synaptic transmission in a common neuroanatomical substrate.

Aging↗

Context-dependent reorganization of spatial and movement representations by simultaneously recorded hippocampal and striatal neurons during performance of allocentric and egocentric tasks.

Hippocampal and striatal place- and movement-correlated cell firing was recorded as rats performed place or response tasks in a familiar environment, and then after cue manipulation. In a familiar environment, place field properties did not differ across brain structures or task conditions. Movement correlates were stronger during place task performance only in hippocampal neurons. After cue manipulations, place- and movement-sensitive hippocampal and striatal neurons changed their correlate strength, regardless of behavioral strategy. Thus, for both structures, place-correlated cells may encode spatial context information, whereas movement-correlated cells may represent both egocentric movement and learned behavioral responses. The striking overall similarity between hippocampal and striatal neural responses to context manipulation (regardless of strategy) suggests that these structures operate continuously, and in parallel, during multiple forms of learning.

Action Potentials↗

Endocannabinoid signaling depends on the spatial pattern of synapse activation.

The brain's endocannabinoid retrograde messenger system decreases presynaptic transmitter release, but its physiological function is uncertain. We show that endocannabinoid signaling is absent when spatially dispersed synapses are activated on rodent cerebellar Purkinje cells but that it reduces presynaptic glutamate release when nearby synapses are active. This switching of signaling according to the spatial pattern of activity is controlled by postsynaptic type I metabotropic glutamate receptors, which are activated disproportionately when glutamate spillover between synapses produces synaptic crosstalk. When spatially distributed synapses are activated, endocannabinoid inhibition of transmitter release can be rescued by inhibiting glutamate uptake to increase glutamate spillover. Endocannabinoid signaling initiated by type I metabotropic glutamate receptors is a homeostatic mechanism that detects synaptic crosstalk and downregulates glutamate release in order to promote synaptic independence.

Animals↗