Role of Astrocytes in Neurovascular Coupling

Neural activity is intimately tied to blood flow in the brain. This coupling is specific enough in space and time that modern imaging methods use local hemodynamics as a measure of brain activity. In this review, we discuss recent evidence indicating that neuronal activity is coupled to local blood flow changes through an intermediary, the astrocyte. We highlight unresolved issues regarding the role of astrocytes and propose ways to address them using novel techniques. Our focus is on cellular level analysis in vivo, but we also relate mechanistic insights gained from ex vivo experiments to native tissue. We also review some strategies to harness advances in optical and genetic methods to study neurovascular coupling in the intact brain

Welcome to Neural Systems and Circuits: bridging the gap between theory and experiment

Molecular and Cellular Biolog

Postnatal Development of Dendrodendritic Inhibition in the Mammalian Olfactory Bulb

The mitral–granule cell (MC–GC) reciprocal synapse is an important source of auto- and lateral-inhibition in the olfactory bulb (OB), and this local inhibition is critical for odor discrimination. We may gain insight into the role of MC autoinhibition in olfaction by correlating the functional development of the autoinhibition with the postnatal development of olfactory function. We have studied the functional development of the MC–GC reciprocal synapse using whole-cell patch-clamp recordings from MCs and GCs in acute OB slices from 3- to 30-day-old rats. The magnitude of dendrodendritic inhibition (DDI) measured by depolarizing a single MC and recording recurrent inhibition in the same cell increased up to the fifteenth day of life (P15), but dropped between P15 and P30. The initial increase and later decrease in DDI was echoed by a similar increase and decrease in the frequency of miniature inhibitory post-synaptic currents, suggesting an accompanying modulation in the number of synapses available to participate in DDI. The late decrease in DDI could also result, in part, from a decrease in GC excitability as well as an increase in relative contribution of N-methyl d-aspartate (NMDA) receptors to γ-amino butyric acid (GABA) release from GC synapses. Changes in release probability of GABAergic synapses are unlikely to account for the late reduction in DDI, although they might contribute to the early increase during development. Our results demonstrate that the functional MC–GC circuit evolves over development in a complex manner that may include both construction and elimination of synapses

Juvenile polyposis syndrome with extraintestinal anomalies: report of a rare case with review of literature

Juvenile polyposis coli is a rare condition in children with neoplastic potential having an incidence of about 1 in 1,00,000 population. A minority of such patients have extraintestinal abnormalities like cardiac and pulmonary arteriovenous malformations. Juvenile polyposis is a disorder of hamartomatous polyposis syndrome having a malignant potential. The progression of hamartomatous polyp to carcinoma is still elucidated when compared to the understanding of transformation of an adenomatous polyp into a carcinoma via a gatekeeper defect. Here is the report of a rare case of Juvenile polyposis in a 7 year old boy who presented with bleeding per rectum and prolapsed rectum showing multiple polyps. Patient had undergone surgery for closure of ventricular septal defect and pulmonary valvotomy 3 years back. Proctocolectomy was done and the resected colon showed 40 polyps. Histologically polyps contained benign glandular tissue and one of the larger polyps showed low grade epithelial dysplasia. In this case, there was no positive family history and extraintestinal congenital defects are said to be more common in such sporadic cases

Calcium dynamics during fertilization in C. elegans

BACKGROUND: Of the animals typically used to study fertilization-induced calcium dynamics, none is as accessible to genetics and molecular biology as the model organism Caenorhabditis elegans. Motivated by the experimental possibilities inherent in using such a well-established model organism, we have characterized fertilization-induced calcium dynamics in C. elegans. RESULTS: Owing to the transparency of the nematode, we have been able to study the calcium signal in C. elegans fertilization in vivo by monitoring the fluorescence of calcium indicator dyes that we introduce into the cytosol of oocytes. In C. elegans, fertilization induces a single calcium transient that is initiated soon after oocyte entry into the spermatheca, the compartment that contains sperm. Therefore, it is likely that the calcium transient is initiated by contact with sperm. This calcium elevation spreads throughout the oocyte, and decays monotonically after which the cytosolic calcium concentration returns to that preceding fertilization. Only this single calcium transient is observed. CONCLUSION: Development of a technique to study fertilization induced calcium transients opens several experimental possibilities, e.g., identification of the signaling events intervening sperm binding and calcium elevation, identifying the possible roles of the calcium elevation such as the completion of meiosis, the formation of the eggshell, and the establishing of the embryo's axis of symmetry

Heterogeneous Release Properties of Visualized Individual Hippocampal Synapses

AbstractWe have used endocytotic uptake of the styryl dye FM1–43 at synaptic terminals (Betz and Bewick 1992) to study properties of individual synapses formed by axons of single hippocampal neurons in tissue culture. The distribution of values for probability of evoked transmitter release pestimated by dye uptake is continuous, with a preponderance of low psynapses and a broad spread of probabilities. We have validated this method by demonstrating that the optically estimated distribution of pat autapses in single-neuron microislands predicts, with no free parameters, the rate of blocking of NMDA responses by the noncompetitive antagonist MK–801 at the same synapses. Different synapses made by a single axon exhibited varying amounts of paired-pulse modulation; synapses with low ptended to be facilitated more than those with high p. The increment in release probability produced by increasing external calcium ion concentration also depended on a synapse's initial p value. The size of the recycling pool of vesicles was strongly correlated with pas well, suggesting that synapses with higher release probabilities had more vesicles. Finally, pvalues of neighboring synapses were correlated, indicating local interactions in the dendrite or axon, or both

Analysis and Synthesis in Olfaction

Natural environments contain numerous volatile compounds emanating from a large number of sources, and the survival of many animals depends on their ability to segregate odors of interest within complex odorous scenes. In a recent paper, we described how the ability of mice to detect odors within mixtures depends on the chemical structure and neural representation of the target and background odorants

An Olfactory Cocktail Party: Figure-Ground Segregation of Odorants in Rodents

In odorant-rich environments, animals must be able to detect specific odorants of interest against variable backgrounds. However, studies have found that both humans and rodents are poor at analyzing the components of odorant mixtures, suggesting that olfaction is a synthetic sense in which mixtures are perceived holistically. We found that mice could be easily trained to detect target odorants embedded in unpredictable and variable mixtures. To relate the behavioral performance to neural representation, we imaged the responses of olfactory bulb glomeruli to individual odors in mice expressing the $Ca^{2+}$ indicator GCaMP3 in olfactory receptor neurons. The difficulty of segregating the target from the background depended strongly on the extent of overlap between the glomerular responses to target and background odors. Our study indicates that the olfactory system has powerful analytic abilities that are constrained by the limits of combinatorial neural representation of odorants at the level of the olfactory receptors.Molecular and Cellular Biolog

Functional Properties of Cortical Feedback Projections to the Olfactory Bulb

SummarySensory perception is not a simple feed-forward process, and higher brain areas can actively modulate information processing in “lower” areas. We used optogenetic methods to examine how cortical feedback projections affect circuits in the first olfactory processing stage, the olfactory bulb. Selective activation of back projections from the anterior olfactory nucleus/cortex (AON) revealed functional glutamatergic synaptic connections on several types of bulbar interneurons. Unexpectedly, AON axons also directly depolarized mitral cells (MCs), enough to elicit spikes reliably in a time window of a few milliseconds. MCs received strong disynaptic inhibition, a third of which arises in the glomerular layer. Activating feedback axons in vivo suppressed spontaneous as well as odor-evoked activity of MCs, sometimes preceded by a temporally precise increase in firing probability. Our study indicates that cortical feedback can shape the activity of bulbar output neurons by enabling precisely timed spikes and enforcing broad inhibition to suppress background activity

Olfactory cortical neurons read out a relative time code in the olfactory bulb

Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that the identity of activated neurons as well as the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains debated. We addressed this question by measuring the spiking activity of downstream neurons while optogenetically stimulating two foci in the olfactory bulb with varying relative timing in mice. We found that the overall spike rates of piriform cortex neurons were sensitive to the relative timing of activation. Posterior piriform cortex neurons showed higher sensitivity to relative input times than neurons in the anterior piriform cortex. In contrast, olfactory bulb neurons rarely showed such sensitivity. Thus, the brain can transform a relative time code in the periphery into a firing-rate-based representation in central brain areas, providing evidence for the relevance of relative time-based code in the olfactory bulb