An in vivo biosensor for neurotransmitter release and in situ receptor activity.

Tools from molecular biology, combined with in vivo optical imaging techniques, provide new mechanisms for noninvasively observing brain processes. Current approaches primarily probe cell-based variables, such as cytosolic calcium or membrane potential, but not cell-to-cell signaling. We devised cell-based neurotransmitter fluorescent engineered reporters (CNiFERs) to address this challenge and monitor in situ neurotransmitter receptor activation. CNiFERs are cultured cells that are engineered to express a chosen metabotropic receptor, use the G(q) protein-coupled receptor cascade to transform receptor activity into a rise in cytosolic [Ca(2+)] and report [Ca(2+)] with a genetically encoded fluorescent Ca(2+) sensor. The initial realization of CNiFERs detected acetylcholine release via activation of M1 muscarinic receptors. We used chronic implantation of M1-CNiFERs in frontal cortex of the adult rat to elucidate the muscarinic action of the atypical neuroleptics clozapine and olanzapine. We found that these drugs potently inhibited in situ muscarinic receptor activity

Modeling of Spiking-Bursting Neural Behavior Using Two-Dimensional Map

A simple model that replicates the dynamics of spiking and spiking-bursting activity of real biological neurons is proposed. The model is a two-dimensional map which contains one fast and one slow variable. The mechanisms behind generation of spikes, bursts of spikes, and restructuring of the map behavior are explained using phase portrait analysis. The dynamics of two coupled maps which model the behavior of two electrically coupled neurons is discussed. Synchronization regimes for spiking and bursting activity of these maps are studied as a function of coupling strength. It is demonstrated that the results of this model are in agreement with the synchronization of chaotic spiking-bursting behavior experimentally found in real biological neurons.Comment: 9 pages, 12 figure

Lasing without inversion in three-level systems without external coherent driving

We have studied an incoherently pumped laser operating with a Doppler-broadened three-level system placed in a doubly resonant cavity. This system generates two laser fields, one of them without population inversion. Both ladder and V-type three-level schemes are considered with a ratio R=ωα/ωβ of inversionless laser frequency ωα to ordinary laser frequency ωβ of R=0.67 and R=1.88, respectively. Dual-wavelength lasing extends up to Doppler-broadening values for optical transitions of atoms in a vapor cell. Some considerations for the practical realization of this dual-wavelength laser are discussed

Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion

A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology

Tactile Discrimination Using Template Classifiers: Towards a Model of Feature Extraction in Mammalian Vibrissal Systems

Rats and other whiskered mammals are capable of making sophisticated sensory discriminations using tactile signals from their facial whiskers (vibrissae). As part of a programme of work to develop biomimetic technologies for vibrissal sensing, including whiskered robots, we are devising algorithms for the fast extraction of object parameters from whisker deflection data. Previous work has demonstrated that radial distance to contact can be estimated from forces measured at the base of the whisker shaft. We show that in the case of a moving object contacting a whisker, the measured force can be ambiguous in distinguishing a nearby object moving slowly from a more distant object moving rapidly. This ambiguity can be resolved by simultaneously extracting object position and speed from the whisker deflection time series – that is by attending to the dynamics of the whisker’s interaction with the object. We compare a simple classifier with an adaptive EM (Expectation Maximisation) classifier. Both systems are effective at simultaneously extracting the two parameters, the EM-classifier showing similar performance to a handpicked template classifier. We propose that adaptive classification algorithms can provide insights into the types of computations performed in the rat vibrissal system when the animal is faced with a discrimination task

Stable Propagation of a Burst Through a One-Dimensional Homogeneous Excitatory Chain Model of Songbird Nucleus HVC

We demonstrate numerically that a brief burst consisting of two to six spikes can propagate in a stable manner through a one-dimensional homogeneous feedforward chain of non-bursting neurons with excitatory synaptic connections. Our results are obtained for two kinds of neuronal models, leaky integrate-and-fire (LIF) neurons and Hodgkin-Huxley (HH) neurons with five conductances. Over a range of parameters such as the maximum synaptic conductance, both kinds of chains are found to have multiple attractors of propagating bursts, with each attractor being distinguished by the number of spikes and total duration of the propagating burst. These results make plausible the hypothesis that sparse precisely-timed sequential bursts observed in projection neurons of nucleus HVC of a singing zebra finch are intrinsic and causally related.Comment: 13 pages, 6 figure

Statistical mechanics of temporal association in neural networks with transmission delays

We study the representation of static patterns and temporal sequences in neural networks with signal delays and a stochastic parallel dynamics. For a wide class of delay distributions, the asymptotic network behavior can be described by a generalized Gibbs distribution, generated by a novel Lyapunov functional for the determination dynamics. We extend techniques of equilibrium statistical mechanics so as to deal with time-dependent phenomena, derive analytic results for both retrieval quality and storage capacity, and compare them with numerical simulations

Gain without population inversion in V-type systems driven by a frequency-modulated field

We obtain gain of the probe field at multiple frequencies in a closed three-level V-type system using frequency modulated pump field. There is no associated population inversion among the atomic states of the probe transition. We describe both the steady-state and transient dynamics of this system. Under suitable conditions, the system exhibits large gain simultaneously at series of frequencies far removed from resonance. Moreover, the system can be tailored to exhibit multiple frequency regimes where the probe experiences anomalous dispersion accompanied by negligible gain-absorption over a large bandwidth, a desirable feature for obtaining superluminal propagation of pulses with negligible distortion.Comment: 10 pages + 8 figures; To appear in Physical Review

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page