A dynamic model for delta rhythm fit to high-frequency cortical activity data shows discrete functional connectivity in mouse cortex

Spontaneous activity as recorded by fMRI has often been used to infer active connections (\u27functional connectivity\u27) in the human brain through correlations of activity measures. Some serious questions have been raised about the interpretation of these correlations, which are often apparent only on time scales of tens of seconds. Confirmation of correlations in measures of activity on shorter time-scales closer to those of neural activity would be very desirable. Numerous mechanisms have been proposed for various rhythms but in the past half-century little consensus has been reached on the mechanism of any major rhythm. The recent development of high-throughput imaging methods enable us for the first time to rigorously and quantitatively test ideas about the dynamics of brain rhythms. We have generated high-resolution data on neural activity over most of one hemisphere of mouse cortex by voltage-sensitive dyes, in both anesthetized and awake animals. In previous work [1] we have analyzed relations between activity measures at different locations in terms of correlations. Here we fit these data to a predictive model, in which we attempt to predict the next change in activity at every point on cortex from the current pattern of activity over cortex. We fit both linear and non-linear models, whose parameters represent the intrinsic dynamics of local cortical regions and the inputs from distal regions. We find that all regions of mouse cortex appear to have virtually identical patterns of intrinsic dynamics (Figure 1A). We find that even a simple linear fit gives surprisingly sparse patterns of inferred connectivity. Where we have clear anatomical information, these fitted patterns appear to match known anatomy. Furthermore this fit can be used to identify the most prominent functional inputs into anatomically diffusely-connected areas such as the parietal association area (Figure 1B). Poster presentation from the Twenty Third Annual Computational Neuroscience Meeting: CNS*201

Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex.

Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex

In vivo Large-Scale Cortical Mapping Using Channelrhodopsin-2 Stimulation in Transgenic Mice Reveals Asymmetric and Reciprocal Relationships between Cortical Areas

We have mapped intracortical activity in vivo independent of sensory input using arbitrary point channelrhodopsin-2 (ChR2) stimulation and regional voltage sensitive dye imaging in B6.Cg-Tg (Thy1-COP4/EYFP)18Gfng/J transgenic mice. Photostimulation of subsets of deep layer pyramidal neurons within forelimb, barrel, or visual primary sensory cortex led to downstream cortical maps that were dependent on synaptic transmission and were similar to peripheral sensory stimulation. ChR2-evoked maps confirmed homotopic connections between hemispheres and intracortical sensory and motor cortex connections. This ability of optogentically activated subpopulations of neurons to drive appropriate downstream maps suggests that mechanisms exist to allow prototypical cortical maps to self-assemble from the stimulation of neuronal subsets. Using this principle of map self-assembly, we employed ChR2 point stimulation to map connections between cortical areas that are not selectively activated by peripheral sensory stimulation or behavior. Representing the functional cortical regions as network nodes, we identified asymmetrical connection weights in individual nodes and identified the parietal association area as a network hub. Furthermore, we found that the strength of reciprocal intracortical connections between primary and secondary sensory areas are unequal, with connections from primary to secondary sensory areas being stronger than the reciprocal

Radiologic manifestations of pulmonary tuberculosis in patients of intensive care units

AbstractBackgroundTuberculosis (TB) is a serpent disease with various pulmonary manifestations, and timely diagnosis of the disease is paramount, since delayed treatment is associated with severe morbidity, particularly in intensive care units (ICU). Therefore, it is imperative that intensivists understand the typical distribution, patterns, and imaging manifestations of TB.AimTo describe different manifestations of pulmonary TB in patients in the ICU.MethodsIn a retrospective study, all patients with a clinical and a laboratory-confirmed diagnosis of TB who were admitted to the ICU were entered in the study. All patients had a confirmatory laboratory diagnosis of TB including positive smears. The patterns of parenchymal lesions, involved segments and presence of cavity, bronchiectasis and bronchogenic spread of the lesions with computed tomography (CT) and chest/X-ray (CXR) were recorded and analyzed.ResultsData of 146 patients with TB were entered in the study. The most common finding in CT was acute respiratory distress syndrome (ARDS)-like radiologic manifestations (17.1%), followed by parenchymal nodular infiltration (13.6%) and cavitation (10.9%), consolidation (10.2%), interstitial involvement (9.5%), calcified parenchymal mass (8.3%), ground-glass opacities (7.5%), and pleural effusion or thickening (6.9%). Radiologic evidence of lymphadenopathy was seen in up to 43% of adults. Miliary TB was observed in 2.3% of patients, mostly in those older than 60years of age. ARDS-like (64.5%) manifestations on CT and miliary TB (85.5%) had the highest mortality rates among other pulmonary manifestations.ConclusionARDS, interstitial involvement, and Parenchymal nodular infiltration are the most common manifestations of pulmonary TB. Various features of TB in ICU patients could be misleading for intensivists

An Id-like current that is downregulated by Ca2+ modulates information coding at CA3–CA3 synapses in the rat hippocampus

Voltage-gated K+ channels localised on presynaptic nerve terminals control information coding by modulating presynaptic firing and synaptic efficacy in target neurones. We found that at CA3–CA3 connections in hippocampal slice cultures, a fast-activating, slowly inactivating K+ conductance similar to the so-called delay current (ID) is responsible for the delayed appearance of the first spike upon membrane depolarisation, for action potential repolarisation and for modulation of transmitter release. The Id-like current was downregulated by intracellular Ca2+, as indicated by the increased delay in the appearance of the first action potential following either the block of Ca2+ flux through voltage-dependent Ca2+ channels with Cd2+ or replacement of the bathing solution with one devoid of Ca2+. In both cases, this effect was reversed by blocking this conductance with a low concentration of 4-aminopyridine (4-AP, 10-50 μM). Application of 4-AP shortened the delay to the first spike generation, prevented the effect of Cd2+ and increased the spike duration. The earlier appearance of the first action potential was also observed in the presence of dendrotoxin-1 (100 nM). In voltage-clamp experiments larger currents were recorded in the absence of extracellular Ca2+, thus confirming the downregulation of the Id-like current by Ca2+ due to the positive shift of its inactivation. Spike broadening was associated with an enhancement of synaptic efficacy in target neurones, as assessed by the increase in EPSC amplitude and in the percentage of successes. Moreover, in the presence of 4-AP, EPSCs appeared with a longer latency and were more scattered. This conductance is therefore crucial for setting the timing and strength of synaptic transmission at CA3–CA3 connections. It is conceivable that switching off ID by increasing intracellular Ca2+ following activity-dependent processes may facilitate network synchronisation and crosstalk between CA3 pyramidal cells, leading to seizure activity

In silico exploration of mouse brain dynamics by focal stimulation reflects the organization of functional networks and sensory processing

International audienceResting-state functional networks such as the default mode network (DMN) dominate spontaneous brain dynamics. To date, the mechanisms linking brain structure and brain dynamics and functions in cognition, perception, and action remain unknown, mainly due to the uncontrolled and erratic nature of the resting state. Here we used a stimulation paradigm to probe the brain's resting behavior, providing insights on state-space stability and multiplicity of network trajectories after stimulation. We performed explorations on a mouse model to map spatiotemporal brain dynamics as a function of the stimulation site. We demonstrated the emergence of known functional networks in brain responses. Several responses heavily relied on the DMN and were suggestive of the DMN playing a mechanistic role between functional networks. We probed the simulated brain responses to the stimulation of regions along the information processing chains of sensory systems from periphery up to primary sensory cortices. Moreover, we compared simulated dynamics against in vivo brain responses to optogenetic stimulation. Our results underwrite the importance of anatomical connectivity in the functional organization of brain networks and demonstrate how functionally differentiated information processing chains arise from the same system