Gating information by two-state membrane potential fluctuations.

Two-state voltage fluctuations between a hyperpolarized down-state and a depolarized up-state have been observed experimentally in a wide variety of neurons across brain regions. Using a biophysical model, we show that synaptic input by NMDA receptors can cause such membrane potential fluctuations. In this model, when a neuron is driven by two input pathways with different AMPA/NMDA receptor content, the NMDA-rich input causes up-state transitions, whereas the AMPA-rich input generates spikes only in the up-state. Therefore the NMDA-rich pathway can gate input from an AMPA pathway in an all-or-none fashion by switching between different membrane potential states. Furthermore, once in the up-state, the NMDA-rich pathway multiplicatively increases the gain of a neuron responding to AMPA-rich input. This proposed mechanism for two-state fluctuations directly suggests specific computations, such as gating and gain modulation based on the distinct receptor composition of different neuronal pathways. The dynamic gating of input by up- and down-states may be an elementary operation for the selective routing of signals in neural circuits, which may explain the ubiquity of two-state fluctuations across brain regions.

Theta oscillations in human cortex during a working-memory task: evidence for local generators.

Cortical theta appears important in sensory processing and memory. Intracanial electrode recordings provide a high spatial resolution method for studying such oscillations during cognitive tasks. Recent work revealed sites at which oscillations in the theta range (4-12 Hz) could be gated by a working-memory task: theta power was increased at task onset and continued until task offset. Using a large data set that has now been collected (10 participants/619 recording sites), we have sufficient sampling to determine how these gated sites are distributed in the cortex and how they are synchronized. A substantial fraction of sites in occipital/parietal (45/157) and temporal (23/280) cortices were gated by the task. Surprisingly, this aspect of working-memory function was virtually absent in frontal cortex (2/182). Coherence measures were used to analyze the synchronization of oscillations. We suspected that because of their coordinate regulation by the working-memory task, gated sites would have synchronized theta oscillations. We found that, whereas nearby gated sites (<20 mm) were often but not always coherent, distant gated sites were almost never coherent. Our results imply that there are local mechanisms for the generation of cortical theta.

Distinct patterns of brain oscillations underlie two basic parameters of human maze learning.

We examine how oscillations in the intracranial electroencephalogram (iEEG) relate to human maze learning. Theta- band activity (4-12 Hz in rodents; 4-8 Hz in humans) plays a significant role in memory function in rodents and in humans. Recording intracranially in humans, we have reported task-related, theta-band rhythmic activity in the raw trace during virtual maze learning and during a nonspatial working memory task. Here we analyze oscillations during virtual maze learning across a much broader range of frequencies and analyze their relationship to two task variables relevant to learning. We describe a new algorithm for detecting oscillatory episodes that takes advantage of the high signal-to-noise ratio and high temporal resolution of the iEEG. Accounting for the background power spectrum of the iEEG, the algorithm allows us to directly compare levels of oscillatory activity across frequencies within the 2- to 45-Hz band. We report that while episodes of oscillatory activity are found at various frequencies, most of the rhythmic activity during virtual maze learning occurs within the theta band. Theta oscillations are more prevalent when the task is made more difficult (manipulation of maze length). However, these oscillations do not tend to covary significantly with decision time, a good index of encoding and retrieval operations. In contrast, lower- and higher-frequency oscillations do covary with this variable. These results suggest that while human cortically recorded theta might play a role in encoding, the overall levels of theta oscillations tell us little about the immediate demands on encoding or retrieval. Finally, different patterns of oscillations may reflect distinct underlying aspects of memory function.

Gating of human theta oscillations by a working memory task.

Electrode grids on the cortical surface of epileptic patients provide a unique opportunity to observe brain activity with high temporal-spatial resolution and high signal-to-noise ratio during a cognitive task. Previous work showed that large-amplitude theta frequency oscillations occurred intermittently during a maze navigation task, but it was unclear whether theta related to the spatial or working memory components of the task. To determine whether theta occurs during a nonspatial task, we made recordings while subjects performed the Sternberg working memory task. Our results show event-related theta and reveal a new phenomenon, the cognitive "gating" of a brain oscillation: at many cortical sites, the amplitude of theta oscillations increased dramatically at the start of the trial, continued through all phases of the trial, including the delay period, and decreased sharply at the end. Gating could be seen in individual trials and varying the duration of the trial systematically varied the period of gating. These results suggest that theta oscillations could have an important role in organizing multi-item working memory.

The Drosophila UBC9 homologue lesswright mediates the disjunction of homologues in meiosis I.

BACKGROUND: In Saccharomyces cerevisiae and other organisms, the UBC9 (ubiquitin-conjugating 9) protein modifies the function of many different target proteins through covalent attachment of the ubiquitin-like protein SMT-3/SUMO. RESULTS: Using a second-site suppression screen of a mutation in the nod locus with a variable meiotic phenotype, we have identified mutations in the Drosophila melanogaster UBC9 homologue, encoded by the gene lesswright (lwr). lwr mutations dominantly suppress the nondisjunction and cytological defects of female meiotic mutations that affect spindle formation. The lwr lethal phenotype is rescued by a Drosophila UBC9/lwr transgene. CONCLUSIONS: We suggest that LWR mediates the dissociation of heterochromatic regions of homologues at the end of meiotic prophase I. Our model proposes that when there is less LWR protein, homologues remain together longer, allowing for more normal spindle formation in mutant backgrounds and therefore more accurate meiotic chromosome segregation.

Reinforcement of family planning service strategy in India.

PIP: The efforts of the Center for Population Studies at the Administrative Staff College of India offer an excellent example of the way in which resources available in the public and private sectors can be brought together to strengthen national population programs. Since the late 1960s the Administrative Staff College of India has been involved in population programs, and these activities coalesced into the Center for Population Studies which was formally established in 1972. The 1st task of the Center for Population Studies was to provide management inputs into the State of Karnataka for the India Population Project. The attempt was made to build up expertise through research and to subsequently transfer this to operating programs through management training and management consultancy. The delivery of services was identified as the priority area for the Center. The Primary Health Center (PHC) is the biggest component of the delivery system, yet there was little understanding of the working of the PHCs and their problems. Studies were launched to correct this deficiency and this led to a series of training programs for PHC doctors. Along with studying PHCs, the Center was asked to look into the program at higher levels, and this led to a study of the Health Department of the State of Karnataka and its subsequent reorganization. Similar efforts are now underway in several other States of India. The 3rd area of the Center's efforts is hospital administration, and studies have been conducted concerning the management fo hospital systems and training programs offered.^ieng