Age-dependent aneuploidy in mammalian oocytes instigated at the second meiotic division.

Ageing severely affects the chromosome segregation process in human oocytes resulting in aneuploidy, infertility and developmental disorders. A considerable amount of segregation errors in humans are introduced at the second meiotic division. We have here compared the chromosome segregation process in young adult and aged female mice during the second meiotic division. More than half of the oocytes in aged mice displayed chromosome segregation irregularities at anaphase II, resulting in dramatically increased level of aneuploidy in haploid gametes, from 4% in young adult mice to 30% in aged mice. We find that the post-metaphase II process that efficiently corrects aberrant kinetochore-microtubule attachments in oocytes in young adult mice is approximately 10-fold less efficient in aged mice, in particular affecting chromosomes that show small inter-centromere distances at the metaphase II stage in aged mice. Our results reveal that post-metaphase II processes have critical impact on age-dependent aneuploidy in mammalian eggs.

Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist.

Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2-3.

Relating information, encoding and adaptation: decoding the population firing rate in visual areas 17/18 in response to a stimulus transition.

Neurons in the primary visual cortex typically reach their highest firing rate after an abrupt image transition. Since the mutual information between the firing rate and the currently presented image is largest during this early firing period it is tempting to conclude this early firing encodes the current image. This view is, however, made more complicated by the fact that the response to the current image is dependent on the preceding image. Therefore we hypothesize that neurons encode a combination of current and previous images, and that the strength of the current image relative to the previous image changes over time. The temporal encoding is interesting, first, because neurons are, at different time points, sensitive to different features such as luminance, edges and textures; second, because the temporal evolution provides temporal constraints for deciphering the instantaneous population activity. To study the temporal evolution of the encoding we presented a sequence of 250 ms stimulus patterns during multiunit recordings in areas 17 and 18 of the anaesthetized ferret. Using a novel method we decoded the pattern given the instantaneous population-firing rate. Following a stimulus transition from stimulus A to B the decoded stimulus during the first 90ms was more correlated with the difference between A and B (B-A) than with B alone. After 90ms the decoded stimulus was more correlated with stimulus B than with B-A. Finally we related our results to information measures of previous (B) and current stimulus (A). Despite that the initial transient conveys the majority of the stimulus-related information; we show that it actually encodes a difference image which can be independent of the stimulus. Only later on, spikes gradually encode the stimulus more exclusively.

Cortical Membrane Potential Dynamics and Laminar Firing during Object Motion.

When an object is introduced moving in the visual field of view, the object maps with different delays in each of the six cortical layers in many visual areas by mechanisms that are poorly understood. We combined voltage sensitive dye (VSD) recordings with laminar recordings of action potentials in visual areas 17, 18, 19 and 21 in ferrets exposed to stationary and moving bars. At the area 17/18 border a moving bar first elicited an ON response in layer 4 and then ON responses in supragranular and infragranular layers, identical to a stationary bar. Shortly after, the moving bar mapped as moving synchronous peak firing across layers. Complex dynamics evolved including feedback from areas 19/21, the computation of a spatially restricted pre-depolarization (SRP), and firing in the direction of cortical motion prior to the mapping of the bar. After 350 ms, the representations of the bar (peak firing and peak VSD signal) in areas 19/21 and 17/18 moved over the cortex in phase. The dynamics comprise putative mechanisms for automatic saliency of novel moving objects, coherent mapping of moving objects across layers and areas, and planning of catch-up saccades.

Cortical dynamics subserving visual apparent motion.

Motion can be perceived when static images are successively presented with a spatial shift. This type of motion is an illusion and is termed apparent motion (AM). Here we show, with a voltage sensitive dye applied to the visual cortex of the ferret, that presentation of a sequence of stationary, short duration, stimuli which are perceived to produce AM are, initially, mapped in areas 17 and 18 as separate stationary representations. But time locked to the offset of the 1st stimulus, a sequence of signals are elicited. First, an activation traverses cortical areas 19 and 21 in the direction of AM. Simultaneously, a motion dependent feedback signal from these areas activates neurons between areas 19/21 and areas 17/18. Finally, an activation is recorded, traveling always from the representation of the 1st to the representation of the next or succeeding stimuli. This activation elicits spikes from neurons situated between these stimulus representations in areas 17/18. This sequence forms a physiological mechanism of motion computation which could bind populations of neurons in the visual areas to interpret motion out of stationary stimuli.

Cortical feedback depolarization waves: a mechanism of top-down influence on early visual areas.

Despite the lack of direct evidence, it is generally believed that top-down signals are mediated by the abundant feedback connections from higher- to lower-order sensory areas. Here we provide direct evidence for a top-down mechanism. We stained the visual cortex of the ferret with a voltage-sensitive dye and presented a short-duration contrast square. This elicited an initial feedforward and lateral spreading depolarization at the square representation in areas 17 and 18. After a delay, a broad feedback wave (FBW) of neuron peak depolarization traveled from areas 21 and 19 toward areas 18 and 17. In areas 18 and 17, the FBW contributed the peak depolarization of dendrites of the neurons representing the square, after which the neurons decreased their depolarization and firing. Thereafter, the peak depolarization surrounded the figure representation over most of areas 17 and 18 representing the background. Thus, the FBW is an example of a well behaved long-range communication from higher-order visual areas to areas 18 and 17, collectively addressing very large populations of neurons representing the visual scene. Through local interaction with feedforward and lateral spreading depolarization, the FBW differentially activates neurons representing the object and neurons representing the background.

Visual areas in the lateral temporal cortex of the ferret (Mustela putorius).

Using systematic electrophysiological mapping, architectonics and the global pattern of interhemispheric connectivity, we have identified three visual areas in the lateral most part of the posterior suprasylvian gyrus. The most posterior and largest area we call area 20a and anterior to this we defined a smaller area, area 20b. These areas lie lateral to the visual areas 18, 19 and 21 and posterior to a third, but incompletely defined, visual area, area PS. Areas 20a and 20b, emphasize the representation of the upper hemifield. Their interhemispheric connections conform to the so called 'midline rule' in that they are abundant in regions representing central portions of the visual field, scarce or absent elsewhere. These areas are probably homologous to the homonymous areas of the cat and might be indicative of a Bauplan from which the temporal areas of primates may have evolved.