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Biomedical subjects

W Singer

Publications and source records attributed to W Singer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Lack of association between thyroid and pineal responses to antidepressant treatment.

With antidepressant treatment for major depression there are decreases in thyroid hormone levels and increases in pineal function. We have conducted a study to examine whether there is a relationship between pineal and thyroid hormone measures as well as between hormone measures and response to treatment in patients treated with desipramine. Measures of thyroid activity included thyroxine, triiodothyronine, T3 resin uptake, and TSH. Pineal function was determined by measurement of 6-suphatoxymelatonin in three consecutive 8 hour pools. Hormone measures as well as Hamilton depression scores were obtained prior to treatment and at the end of 5 weeks of treatment. As in previous studies, thyroid measures decreased, pineal activity increased, and Hamilton scores decreased significantly with treatment. No correlations were found between these measures, suggesting that if there is a relationship between them it is not a direct one.

Adult↗
PubMed1996

The influence of temporal phase differences on texture segmentation.

Scene segmentation and perceptual grouping are important operations in visual processing. Pattern elements constituting individual perceptual objects need to be segregated from those of other objects and the background and have to be bound together for further joint evaluation. Both textural (spatial) and temporal cues are exploited for this grouping operation. Thus, pattern elements might get bound that share certain textural features and/or appear in close spatial or temporal contiguity. However, results on the involvement of temporal cues in perceptual grouping are contradictory [Kiper et al. (1991). Society for Neuroscience Abstracts, 17, 1209; Fahle (1993). Proceedings of the Royal Society of London B, 254, 199-203]. We therefore reinvestigated the relative contributions of temporal and spatial cues and their interactions in a texture-segmentation paradigm. Our data show that the visual system can segregate figures solely on the basis of temporal cues if the temporal offset between figure and ground elements exceeds 10 msec. Moreover, segregation of figures defined by orientation differences among pattern elements is facilitated by additional temporal cues if these define the same figure. If temporal and textural cues define different figures, the two cues compete and only the more salient pattern is perceived. By contrast, the detection of a figure defined by orientation is not impaired by conflicting temporal cues if these do not define a figure themselves and do not exceed offset intervals of 100 msec. These results indicate the existence of a flexible binding mechanism that exploits both temporal and textural cues either alone or in combination if they serve perceptual grouping but can exclude either of the two cues if they are in conflict or do not define a figure. It is proposed that this flexibility is achieved by the implementation of two segmentation mechanisms which differ in their sensitivity for spatial and temporal cues and interact in a facultative way.

Adult↗
PubMed1996

Involvement of silent synapses in the induction of long-term potentiation and long-term depression in neocortical and hippocampal neurons.

Changes in the latency of small excitatory postsynaptic potentials were observed in association with induction of long-term modifications of synaptic transmission in slices of rat neocortex and guinea-pig hippocampus. After potentiation response latency decreased in 3/10 cases in the neocortex and in 6/24 cases in the hippocampus, and increased after depression in 4/8 cases in the neocortex. These latency changes could not be attributed to changes in presynaptic fibre excitability, monosynaptic inhibition, release kinetics or activation kinetics of postsynaptic ion channels. We conclude therefore that potentiation led to the activation of previously silent synapses of fast-conducting afferents and depression to the inactivation of previously functional synapses. Thus, neocortical and hippocampal synapses can be in a non-functional state, and regimes that induce long-term potentiation and depression not only change the efficacy of synapses but also alter their functional state.

Animals↗
PubMed1996

Integrator or coincidence detector? The role of the cortical neuron revisited.

Neurons can operate in two distinct ways, depending on the duration of the interval over which they effectively summate incoming synaptic potentials. If this interval is of the order of the mean interspike interval or longer, neurons act effectively as temporal integrators and transmit temporal patterns with only low reliability. If, by contrast, the integration interval is short compared to the interspike interval, neurons act essentially as coincidence detectors, relay preferentially synchronized input, and the temporal structure of their output is a direct function of the input pattern. Recently, interest in this distinction has been revived because experimental and theoretical results suggest that synchronous firing of neurons might play an important role for information processing in the cortex. Here, we argue that coincidence detection, rather than temporal integration, might be a prevalent operation mode of cortical neurons. We base our arguments on established biophysical properties of cortical neurons and on particular features of cortical dynamics.

Animals↗
PubMed1996

Different threshold levels of postsynaptic [Ca2+]i have to be reached to induce LTP and LTD in neocortical pyramidal cells.

Changes in [Ca2+]i were measured in layer II-III pyramid cells of the rat visual cortex slices during application of either LTP or LTD inducing stimulation protocols. At dendritic sites activated by the stimulated afferents [Ca2+]i reached higher amplitudes and decayed more slowly with LTP than with LTD inducing stimuli. In the presence of Ca2+ chelators, the stimulation protocol that would normally produce LTP induced either LTD or failed to induce a synaptic modifications altogether. These results support the hypothesis that the polarity of synaptic gain changes depends on the magnitude of postsynaptic [Ca2+]i responses, the induction of LTP requiring a more pronounced surge of [Ca2+]i than the induction of LTD.

Afferent Pathways↗
PubMed1996

Brain-derived neurotrophic factor reversed experience-dependent synaptic modifications in kitten visual cortex.

During a critical period of early postnatal development the functional architecture of the visual cortex is shaped by experience-dependent circuit selection following a Hebbian mechanism. One consequence is that monocular deprivation (MD) leads to competitive repression of the input from the deprived eye. Recently it has been proposed that this process might involve activity-dependent competition for neurotrophic substances because the synthesis of brain-derived neurotrophic factor (BDNF) is regulated by visual input. Here we investigate the effects of intracortical infusion of BDNF and nerve growth factor (NGF) on MD effects in the visual cortex. Neuronal responses were monitored with optical and single unit recording techniques in the visual cortex of kittens that had been infused intracortically either with BDNF, NGF or cytochrome C while subjected to MD for 1 week during the peak of the critical period. NGF or cytochrome C had no effect on the consequences of MD. After BDNF treatment, by contrast, ocular dominance (OD) shifted towards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula, and neurons lost their orientation selectivity. At intermediate distances both eyes activated the cortex equally well and responses were again tuned for orientation; at still larger distances OD was shifted towards the normal eye. Thus, BDNF antagonizes the functional effects of MD and at high concentrations causes paradoxical disconnection of non-deprived afferents and a loss of orientation selectivity.

Animals↗
PubMed1996

Calcium-induced long-term depression in the visual cortex of the rat in vitro.

1. In many brain areas, including neocortex and hippocampus, excitatory synapses can undergo both long-term potentiation (LTP) and long-term depression (LTD). It is established that a change in the postsynaptic calcium concentration ([Ca2+]i) is critical for the induction of both LTP and LTD. Protocols that induce these long-term synaptic modifications typically involve afferent stimulation. But, in hippocampus, LTP can also be induced by a transient increase of the extracellular calcium concentration ([Ca2+]o). The purpose of the present study was to determine whether raising [Ca2+]o also induces long-term modifications of excitatory synaptic transmission in the neocortex. 2. Intracellular recordings were obtained from regular spiking cells in layers II-III of slices of the rat visual cortex. Test stimuli were evoked with stimulation electrodes located in the white matter (w.m.) below the recorded cell and intracortically (i.c.) adjacent to the cell. Both the depolarizing slope and the amplitude of excitatory postsynaptic potentials (EPSPs) were measured. For exposure to elevated [Ca2+]o, the normal medium ([Ca2+]o = 2 mM) was exchanged for a period of 10 min against a medium containing 4 mM [Ca2+]o. 3. Elevated [Ca2+]o leads, after return to normal medium, to a long-lasting decrease of intracellularly recorded synaptic responses to both w.m. and i.c. stimulation even if activation of these two pathways is discontinued or N-methyl-D-aspartate (NMDA) receptors are blocked during elevated [Ca2+]o. This decrease is due to reduced efficacy of excitatory transmission because it is observed in the presence of the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline. 4. Induction of LTD by raising [Ca2+]o is voltage dependent. First, elevated [Ca2+]o elicits LTD only in cells whose resting membrane potential (Vmr) is less polarized than -79 mV (and more polarized than -70 mV, which is the Vmr of the least polarized cell). Second, hyperpolarizing cells whose Vmr is in this susceptible range by 20 mV below Vmr during exposure to high [Ca2+]o prevents Ca2+-induced LTD. Third, when elevated [Ca2+]o is associated with postsynaptic depolarizing pulses, LTD is readily induced in cells whose Vmr is more polarized than -79 mV. This voltage dependence implies that the depression is induced by a postsynaptic process and hence that it occurs at synapses formed by excitatory terminals on the recorded neuron. 5. Assuming that a transient elevation of [Ca2+]o leads to an increase of [Ca2+]i, the results of this study suggest that a transient increase of [Ca2+]i is sufficient to elicit LTD. This may provide a mechanism for the induction of heterosynaptic LTD, a depression that occurs in afferents that are silent while the postsynaptic neuron is activated by other inputs.

Animals↗
PubMed1996

Change in thyroid hormone levels following response to cognitive therapy for major depression.

OBJECTIVE: Various somatic antidepressant treatments of depression are associated with substantial but limited decreases in T4 levels. This study examined changes in patients' thyroid hormone levels during a period of cognitive behavior therapy. METHOD: Thyroid hormone levels of 30 patients with major depressive disorder were measured before and after they received 20 weekly sessions of cognitive behavior therapy. RESULTS: There were significant decreases in measures of T4 in the 17 responders to cognitive behavior therapy and increases in the 13 nonresponders. CONCLUSIONS: Cognitive behavior therapy has an effect on the thyroid axis similar to that of somatic antidepressant treatments.

Adult↗
PubMed1995

Stimulus dependent intercolumnar synchronization of single unit responses in cat area 17.

Recent concepts of cortical information processing suggest that visual stimuli are represented by ensembles of synchronously firing neurones. This hypothesis predicts that individual cells in separate columns of the visual cortex should synchronize their discharges in response to a single coherent stimulus and fire asynchronously when each neurone responds to a different stimulus. To test this prediction, we recorded simultaneously with two stereotrodes from single units with non-overlapping, colinearly arranged receptive fields in area 17 of the anaesthetized cat. In support of the hypothesis, cell pairs activated by the same long bar stimulus discharged in synchrony, and fired with no or diminished temporal correlation when each neurone was activated by an independent light bar.

Animals↗
PubMed1995

Development and plasticity of cortical processing architectures.

One of the basic functions of the cerebral cortex is the analysis and representation of relations among the components of sensory and motor patterns. It is proposed that the cortex applies two complementary strategies to cope with the combinatorial problem posed by the astronomical number of possible relations: (i) the analysis and representation of frequently occurring, behaviorally relevant relations by groups of cells with fixed but broadly tuned response properties; and (ii) the dynamic association of these cells into functionally coherent assemblies. Feedforward connections and reciprocal associative connections, respectively, are thought to underlie these two operations. The architectures of both types of connections are susceptible to experience-dependent modifications during development, but they become fixed in the adult. As development proceeds, feedforward connections also appear to lose much of their functional plasticity, whereas the synapses of the associative connections retain a high susceptibility to use-dependent modifications. The reduced plasticity of feedforward connections is probably responsible for the invariance of cognitive categories acquired early in development. The persistent adaptivity of reciprocal connections is a likely substrate for the ability to generate representations for new perceptual objects and motor patterns throughout life.

Action Potentials↗
PubMed1995

All-or-none excitatory postsynaptic potentials in the rat visual cortex.

Intracellular recordings were obtained from supragranular neurons in slices of the rat visual cortex. In approximately 25% of the cells large (0.5-1.6 mV) excitatory postsynaptic potentials (EPSPs) of constant amplitude were observed after minimal, presumably single-fibre stimulation. The amplitude variance of these large EPSPs was surprisingly small and within the range of the variance of the noise. These EPSPs could be reduced in amplitude by paired-pulse and low-frequency stimulation or by raising extracellular Mg2+ concentration. Reduced EPSPs could either continue to behave as all-or-none responses, or they could fluctuate between several amplitude levels. Conversely, responses where the amplitude fluctuated from trial to trial under control conditions could be converted into large all-or-none responses by paired-pulse facilitation. This indicates that the large all-or-none EPSPs were composed of several subunits, probably reflecting the action of several different release sites. It is concluded that these release sites are either independent and operate with a probability close to 1 or, if operating with a lower probability, are coordinated by a mechanism which synchronizes release. Several observations suggest that release probabilities can switch from values close to 1 to 0 with repetitive stimulation or high Mg2+ concentration. Thus, a substantial fraction of single-fibre inputs to supragranular cells possess synapses which operate with high synaptic efficiency and extremely low variance under control conditions but can undergo drastic changes in efficacy when release probabilities are interfered with. Such modifications of release probability could serve as an effective mechanism to regulate the gain of synaptic transmission.

Animals↗
PubMed1995

Involvement of serotonin in developmental plasticity of kitten visual cortex.

During a critical period of postnatal development, neuronal connections in the kitten visual cortex are susceptible to experience-dependent modifications. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To address the question of whether serotonin (5-hydroxytryptamine; 5-HT), the other major neuromodulator in the cerebral cortex, also plays a role in developmental plasticity, we investigated whether interference with serotoninergic transmission in the kitten visual cortex affects ocular dominance (OD) plasticity. The serotonin neurotoxin 5,7-dihydroxytryptamine or the serotonin receptor blockers ketanserin and methysergide were infused into the visual cortex of kittens undergoing monocular deprivation. We found that both methods of disrupting serotoninergic transmission reduced OD plasticity. However, to be effective, the receptor blockers ketanserin and methysergide had to be applied in combination, suggesting that coactivation of serotonin receptor subtypes of both the 5-HT1 and 5-HT2 families have a permissive function in OD plasticity. Since activation of 5-HT2 receptors stimulates phosphoinositide hydrolysis, our data suggest that second messengers from the phospholipid pathway may play an important role in developmental plasticity of visual cortex.

5,7-Dihydroxytryptamine↗
PubMed1995

Metabolic mapping of visual areas in the behaving cat: a [14C]2-deoxyglucose study.

Visually responsive cortical areas and subcortical nuclei were studied in the awake cat using the 2-deoxyglucose technique. Visual input was confined to one hemisphere by unilaterally sectioning the optic tract, the corpus callosum and the commissura anterior. Within the intact hemisphere, numerous cortical regions were distinguishable in the autoradiographs due to differential labelling. Comparison of the intact with the visually deafferented hemisphere confirmed the visual character of eighteen cortical areas (areas 17, 18, 19, 20a, 20b, 21a, 21b, the posteromedial lateral, posterolateral lateral, anteromedial lateral, anterolateral lateral, dorsal lateral, ventral lateral, and posterior suprasylvian areas, the splenial and anterior ectosylvian sylvian areas, insular visual area and posterior area 7) and revealed the visual nature of an area in the posterior cingulate gyrus which had not been described previously. We refer to this area as cingulate visual area (CVA). This area exhibits a gradient in interhemispheric differences along a caudorostral axis similar to that observed in posterior area 7 which is in keeping with the strong and topographic connections between CVA and posterior area 7. These results support the validity of metabolic mapping for the characterisation of cortical areas.

Animals↗
PubMed1995

Relation between oscillatory activity and long-range synchronization in cat visual cortex.

Recent theoretical studies have suggested that oscillatory firing patterns with frequencies in the gamma band (30-70 Hz) may be instrumental for the establishment of synchrony among widely distributed neurons if synchrony is to be achieved by reciprocal connections. We have now investigated the relationship between synchrony and oscillations in cat visual cortex. Our results show that when synchronization of neuronal activity occurs over distances of > 2 mm in primary visual cortex, or occurs between the two hemispheres, it is almost always associated with oscillatory firing patterns, whereas synchronization over short distances occurs also in the absence of oscillations. Furthermore, our results indicate that short-range interactions affect both the firing rate of the respective neurons and the timing of their discharges, whereas only the latter is influenced by long-range interactions. These data support the hypothesis that oscillatory activity can contribute to the establishment of long-range synchrony in a network of reciprocally coupled neurons.

Animals↗
PubMed1995

Thyroid hormone treatment of depression.

The use of thyroid hormones in the treatment of depression is reviewed. The studies examining the use of triodothyronine (T3) alone as well as combination with antidepressants are discussed. The data suggest that there is little evidence that T3 alone has antidepressant efficacy but that this hormone may be used to enhance therapeutic effects of antidepressants in treatment refractory depressed patients. The different theories to explain the antidepressant effects of T3 are summarized.

Antidepressive Agents↗
PubMed1995

How precise is neuronal synchronization?

Recent work suggests that synchronization of neuronal activity could serve to define functionally relevant relationships between spatially distributed cortical neurons. At present, it is not known to what extent this hypothesis is compatible with the widely supported notion of coarse coding, which assumes that features of a stimulus are represented by the graded responses of a population of optimally and suboptimally activated cells. To resolve this issue we investigated the temporal relationship between responses of optimally and suboptimally stimulated neurons in area 17 of cat visual cortex. We find that optimally and suboptimally activated cells can synchronize their responses with a precision of a few milliseconds. However, there are consistent and systematic deviations of the phase relations from zero phase lag. Systematic variation of the orientation of visual stimuli shows that optimally driven neurons tend to lead over suboptimally activated cells. The observed phase lag depends linearly on the stimulus orientation and is, in addition, proportional to the difference between the preferred orientations of the recorded cells. Similar effects occur when testing the influence of the movement direction and the spatial frequency of visual stimuli. These results suggest that binding by synchrony can be used to define assemblies of neurons representing a coarse-coded stimulus. Furthermore, they allow a quantitative test of neuronal network models designed to reproduce physiological results on stimulus-specific synchronization.

Anesthesia↗