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Anna Devor

Publications and source records attributed to Anna Devor.

14 recordsLinked to original sources
PubMed2007

Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation.

The cortical hemodynamic response to somatosensory stimulus is investigated at the level of individual vascular compartments using both depth-resolved optical imaging and in-vivo two-photon microscopy. We utilize a new imaging and spatiotemporal analysis approach that exploits the different characteristic dynamics of responding arteries, arterioles, capillaries and veins to isolate their three-dimensional spatial extent within the cortex. This spatial delineation is validated using vascular casts. Temporal delineation is supported by in-vivo two-photon microscopy of the temporal dynamics and vascular mechanisms of the arteriolar and venous responses. Using these techniques we have been able to characterize the roles of the different vascular compartments in generating and controlling the hemodynamic response to somatosensory stimulus. We find that changes in arteriolar total hemoglobin concentration agree well with arteriolar dilation dynamics, which in turn correspond closely with changes in venous blood flow. For 4-s stimuli, we see only small changes in venous hemoglobin concentration, and do not detect measurable dilation or ballooning in the veins. Instead, we see significant evidence of capillary hyperemia. We compare our findings to historical observations of the composite hemodynamic response from other modalities including functional magnetic resonance imaging. Implications of our results are discussed with respect to mathematical models of cortical hemodynamics, and to current theories on the mechanisms underlying neurovascular coupling. We also conclude that our spatiotemporal analysis approach is capable of isolating and localizing signals from the capillary bed local to neuronal activation, and holds promise for improving the specificity of other hemodynamic imaging modalities.

Animals↗
PubMed2006

Laminar population analysis: estimating firing rates and evoked synaptic activity from multielectrode recordings in rat barrel cortex.

We present a new method, laminar population analysis (LPA), for analysis of laminar-electrode (linear multielectrode) data, where physiological constraints are explicitly incorporated in the mathematical model: the high-frequency band [multiunit activity (MUA)] is modeled as a sum over contributions from firing activity of multiple cortical populations, whereas the low-frequency band [local field potential (LFP)] is assumed to reflect the dendritic currents caused by synaptic inputs evoked by this firing. The method is applied to stimulus-averaged laminar-electrode data from barrel cortex of anesthetized rat after single whisker flicks. Two sample data sets, distinguished by stimulus paradigm, type of applied anesthesia, and electrical boundary conditions, are studied in detail. These data sets are well accounted for by a model with four cortical populations: one supragranular, one granular, and two infragranular populations. Population current source densities (CSDs; the CSD signatures after firing in a particular population) provided by LPA are further used to estimate the synaptic connection pattern between the various populations using a new LFP template-fitting technique, where LFP population templates are found by the electrostatic forward solution based on results from compartmental modeling of morphologically reconstructed neurons. Our analysis confirms previous experimental findings regarding the synaptic connections from neurons in the granular layer onto neurons in the supragranular layers and provides predictions about other synaptic connections. Furthermore, the time dependence of the stimulus-evoked population firing activity is predicted, and the temporal ordering of response onset is found to be compatible with earlier findings.

Action Potentials↗
PubMed2006

Current-source density estimation based on inversion of electrostatic forward solution: effects of finite extent of neuronal activity and conductivity discontinuities.

A new method for estimation of current-source density (CSD) from local field potentials is presented. This inverse CSD (iCSD) method is based on explicit inversion of the electrostatic forward solution and can be applied to data from multielectrode arrays with various geometries. Here, the method is applied to linear-array (laminar) electrode data. Three iCSD methods are considered: the CSD is assumed to have cylindrical symmetry and be (i) localized in infinitely thin discs, (ii) step-wise constant or (iii) continuous and smoothly varying (using cubic splines) in the vertical direction. For spatially confined CSD distributions the standard CSD method, involving a discrete double derivative, is seen in model calculations to give significant estimation errors when the lateral source dimension is comparable to the size of a cortical column (less than approximately 1 mm). Further, discontinuities in the extracellular conductivity are seen to potentially give sizable errors for even wider source distributions. The iCSD methods are seen to give excellent estimates when the correct lateral source dimension and spatial distribution of conductivity are incorporated. To illustrate the application to real data, iCSD estimates of stimulus-evoked responses measured with laminar electrodes in the rat somatosensory (barrel) cortex are compared to estimates from the standard CSD method.

Algorithms↗
PubMed2005

Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex.

The spatial extent of the changes in oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR), total hemoglobin concentration (HbT), cerebral blood flow (CBF), and the cerebral metabolic rate of oxygen (CMRO(2)) in response to forepaw and whisker stimulation were compared in the rat somatosensory cortex using a combination of multi-wavelength reflectance imaging and laser speckle contrast imaging of cerebral blood flow. The spatial extents of the response of each hemodynamic parameter and CMRO(2) were found to be comparable at the time of peak response, and at early times following stimulation onset, the spatial extent of the change in HbR was smaller than that of HbO, HbT, CBF, and CMRO(2). In addition, a slight spatial dependence was found in the power law coefficient relating changes in CBF and HbT. Although the CMRO(2) response is a metabolic measure and thus expected to have a more localized response than the hemodynamic parameters, the results presented here suggest that this may not be the case in general, possibly due to the increased sensitivity of optical imaging techniques to superficial cortical layers where the lateral extent of the metabolic and neuronal activation is larger compared to that in layer IV. In addition, we found that the measured spatial extent of the CMRO(2) changes was insensitive to assumptions made in the calculation of the CMRO(2) changes such as baseline hemoglobin concentrations, vascular weighting constants, and wavelength dependence of tissue scattering. Multi-parameter full field imaging of the functional response provides a more complete picture of the hemodynamic response to functional activation including the spatial and temporal estimation of CMRO(2) changes.

Algorithms↗
PubMed2005

Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging.

Laser speckle contrast imaging is becoming an established method for full-field imaging of cerebral blood flow dynamics in animal models. The sensitivity and noise in the measurement of blood flow changes depend on the camera exposure time. The relation among sensitivity, noise, and camera exposure time was investigated experimentally by imaging the speckle contrast changes in the brain after electrical forepaw stimulation in rats. The sensitivity to relative changes in speckle contrast was found to increase at longer exposure times and to reach a plateau for exposure times greater than approximately 2 ms. However, the speckle contrast noise also increases with exposure time and thus the contrast-to-noise ratio was found to peak at an exposure time of approximately 5 ms. Our results suggests that approximately 5 ms is an optimal exposure time for imaging of stimulus-induced changes in cerebral blood flow in rodents.

Algorithms↗
PubMed2005

Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity.

Accurate interpretation of functional MRI (fMRI) signals requires knowledge of the relationship between the hemodynamic response and the neuronal activity that underlies it. Here we address the question of coupling between pre- and postsynaptic neuronal activity and the hemodynamic response in rodent somatosensory (Barrel) cortex in response to single-whisker deflection. Using full-field multiwavelength optical imaging of hemoglobin oxygenation and electrophysiological recordings of spiking activity and local field potentials, we demonstrate that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns. We demonstrate that the hemodynamic response is a spatiotemporal convolution of the neuronal activation. Therefore, positive hemodynamic response in one cortical column might be explained by neuronal activity not only in that column but also in the neighboring columns. Thus, attempts at characterizing the neurovascular relationship based on point measurements of electrophysiology and hemodynamics may yield inconsistent results, depending on the spatial extent of neuronal activation. The finding that the hemodynamic signal observed at a given location is a function of electrophysiological activity over a broad spatial region helps explain a previously observed increase of local vascular response beyond the saturation of local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin hemodynamic responses can be well approximated by space-time separable functions with an antagonistic center-surround spatial pattern extending over several millimeters. The surround "negative" hemodynamic activity did not correspond to observable changes in neuronal activity. The complex spatial integration of the hemodynamic response should be considered when interpreting fMRI data.

Animals↗
PubMed2003

Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex.

Recent advances in brain imaging techniques, including functional magnetic resonance imaging (fMRI), offer great promise for noninvasive mapping of brain function. However, the indirect nature of the imaging signals to the underlying neural activity limits the interpretation of the resulting maps. The present report represents the first systematic study with sufficient statistical power to quantitatively characterize the relationship between changes in blood oxygen content and the neural spiking and synaptic activity. Using two-dimensional optical measurements of hemodynamic signals, simultaneous recordings of neural activity, and an event-related stimulus paradigm, we demonstrate that (1) there is a strongly nonlinear relationship between electrophysiological measures of neuronal activity and the hemodynamic response, (2) the hemodynamic response continues to grow beyond the saturation of electrical activity, and (3) the initial increase in deoxyhemoglobin that precedes an increase in blood volume is counterbalanced by an equal initial decrease in oxyhemoglobin.

Animals↗
PubMed2003

Deformation of network connectivity in the inferior olive of connexin 36-deficient mice is compensated by morphological and electrophysiological changes at the single neuron level.

Compensatory mechanisms after genetic manipulations have been documented extensively for the nervous system. In many cases, these mechanisms involve genetic regulation at the transcription or expression level of existing isoforms. We report a novel mechanism by which single neurons compensate for changes in network connectivity by retuning their intrinsic electrical properties. We demonstrate this mechanism in the inferior olive, in which widespread electrical coupling is mediated by abundant gap junctions formed by connexin 36 (Cx36). It has been shown in various mammals that this electrical coupling supports the generation of subthreshold oscillations, but recent work revealed that rhythmic activity is sustained in knock-outs of Cx36. Thus, these results raise the question of whether the olivary oscillations in Cx36 knock-outs simply reflect the status of wild-type neurons without gap junctions or the outcome of compensatory mechanisms. Here, we demonstrate that the absence of Cx36 results in thicker dendrites with gap-junction-like structures with an abnormally wide interneuronal gap that prevents electrotonic coupling. The mutant olivary neurons show unusual voltage-dependent oscillations and an increased excitability that is attributable to a combined decrease in leak conductance and an increase in voltage-dependent calcium conductance. Using dynamic-clamp techniques, we demonstrated that these changes are sufficient to transform a wild-type neuron into a knock-out-like neuron. We conclude that the absence of Cx36 in the inferior olive is not compensated by the formation of other gap-junction channels but instead by changes in the cytological and electroresponsive properties of its neurons, such that the capability to produce rhythmic activity is maintained.

Adaptation, Physiological↗
PubMed2003

Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation.

A simple instrument is demonstrated for high-resolution simultaneous imaging of total hemoglobin concentration and oxygenation and blood flow in the brain by combining rapid multiwavelength imaging with laser speckle contrast imaging. The instrument was used to image changes in oxyhemoglobin and deoxyhemoglobin and blood flow during cortical spreading depression and single whisker stimulation in rats through a thinned skull. The ability to image blood flow and hemoglobin concentration changes simultaneously with high resolution will permit detailed quantitative analysis of the spatiotemporal hemodynamics of functional brain activation, including imaging of oxygen metabolism. This is of significance to the neuroscience community and will lead to a better understanding of the interrelationship of neural, metabolic, and hemodynamic processes in normal and diseased brains.

Animals↗
PubMed2003

In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing.

The magnetic resonance imaging (MRI)-detectable T1 contrast agent manganese (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and monkeys. We have tested to what extent this in vivo method is useful for three-dimensional (3-D) survey of connectivity patterns in the rat somatosensory system. A commonly available 3 T human clinical MRI scanner was used to trace neural pathways following focal injection of manganese chloride (MnCl2) in the somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant signal enhancement in major projection systems, including corticocortical, corticostriatal, corticothalamic, corticotectal, corticopontine, and corticospinal pathways. To facilitate the assignment of anatomic localization to the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison using the digital model allowed demonstration of a corticothalamic 3-D topographic organization in agreement with previously published two-dimensional topographic schemes based on classical neural tracing data. We conclude that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning.

Animals↗
PubMed2002

Electrotonic coupling in the inferior olivary nucleus revealed by simultaneous double patch recordings.

Electrotonic coupling in the inferior olivary (IO) nucleus is assumed to play a crucial role in generating the subthreshold membrane potential oscillations in olivary neurons and in synchronizing climbing fiber input into the cerebellar cortex. We studied the strength and spatial distribution of the coupling by simultaneous double patch recordings from olivary neurons in the brain slice preparation. Electrotonic coupling was observed in 50% of the cell pairs. The coupling coefficient (CC), defined as the ratio between voltage responses of the post- and the prejunctional cell, varied between 0.002 and 0.17; most of the pairs were weakly coupled. In more than 75% of the pairs, the CC was <0.05. The coupling resistance varied between 0.7 to 19.8 G(Omega), and 68% of the values fell between 0.7 to 8 G(Omega). The difference between the coupling coefficient measured on stimulation of cell 1 or cell 2 of a coupled pair was 27 +/- 16%. Direct calculation of the coupling resistance revealed an asymmetry of 24 +/- 12%, suggesting a directional preference of coupling. The coupling was voltage independent, although depolarization of either the pre- or the postjunctional neuron reduced the CC. The chance of a cell pair being coupled was 80% in immediate neighboring cells, but dropped to about 30% at a distance of 40 microm. No coupled pairs were observed at distances larger than 70 microm. In 52% of staining experiments neurobiotin injection into an olivary neuron produced indirect labeling of 1-11 nearby cells with an average of 3.8 +/- 2.9. All indirectly labeled cells were found in, or immediately adjacent, to the dendritic field of the directly stained neuron. Two distinct morphological types of olivary neurons, "curly" and "straight" cells, were found. In each case all neurons stained indirectly by dye passage through gap junctions belonged to the same type. Using the physiological data we estimated that each olivary neuron is directly coupled to about 50 neurons. Since somatic recordings may not reveal coupling through remote dendrites, we conclude that each neuron is directly connected to > or =50 neurons forming two distinct networks of curly and straight cells.

Action Potentials↗
PubMed2002

Generation and propagation of subthreshold waves in a network of inferior olivary neurons.

The cells of the inferior olivary (IO) nucleus generate a large repertoire of electrical signals, among them subthreshold oscillations of the membrane potential (STO). To date, subthreshold oscillations have been studied at the level of single-cell recordings, from which network properties were inferred. In this study we used whole cell patch recordings and optical imaging to address the following issues: 1) synchrony of STO in neighboring neurons; 2) stability of the oscillatory activity in the temporal and spatial domain; and 3) the size of the oscillating network. Recordings were made from 126 pairs of IO neurons in 13- to 30-day-old rats. An additional 262 neurons were recorded individually. The frequency of STO varied from 0.8 to 8.6 Hz. The frequency distribution revealed two subpopulations with peaks at about 3 and 6 Hz. The maximum amplitude among the cells varied from 2 to 25 mV. Oscillations in most neurons showed ongoing modulations in both frequency and amplitude. These modulations were largely abolished following bath application of 40 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, suggesting that they were caused by glutamatergic action. In 35 of 61 recorded pairs at least one neuron exhibited STO permitting us to compare frequency and phase relations. In 22 pairs there was coherent activity with zero phase difference between oscillations in the 2 cells. In these pairs, frequency and amplitude modulation occurred simultaneously in both neurons. Electrotonic coupling was tested in 13 pairs, that had coherent STO, and it was detected in 12. An additional seven pairs showed coherent oscillations but with a phase difference of 20-50 ms. Electrotonic coupling was observed in three of these pairs. Electrotonic coupling was also observed in two of five pairs in which only one neuron oscillated. No coupling was detected in one pair where both neurons oscillated but at different frequencies. Optical imaging using a voltage-sensitive dye (RH 414) was performed on 40 IO slices using an array of 128 photodiodes. Patches of oscillatory activity were observed in 10 slices. Among them six showed spontaneous oscillations, and four exhibited oscillations following extracellular stimulation. In agreement with cell pair recording, optical imaging demonstrated phase-shifted activity in the form of propagating waves of activity within an oscillating patch. We conclude that 1) STO exhibit ongoing modulations of frequency and amplitude that are probably caused by extrinsic inputs to the IO nucleus; 2) electrotonically coupled neurons show a high level of STO synchrony; and 3) the oscillatory activity can propagate within a network of coupled olivary neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMedDate not supplied

The great gate: control of sensory information flow to the cerebellum.

An evident feature of the physiology of the inferior olivary nucleus is modulation of the responsiveness of neurons to peripheral stimulation by the behavioral state of the subject animal. The olivary response to self-generated sensory inputs, as well as to input predictable from association with other stimuli, is suppressed. This suppression occurs in part at the level of the inferior olivary nucleus itself. On the other hand, the cells respond readily to sensory inputs that are not anticipated. On a cellular level inferior olivary neurons exhibit two properties that might account for information gating. The first one is the organization of synaptic inputs on olivary spines in glomerular structures, where extrinsic inhibitory and excitatory inputs, confined to the same olivary dendritic spine, can efficiently cancel each other if they arrive within a certain time window. About half of the inhibitory inputs to olivary glomeruli originate in the deep cerebellar nuclei and are regarded as an inhibitory feedback. The second property is subthreshold membrane potential oscillations, a property of the electrotonically coupled olivary network. Extrinsic synaptic inputs to the nucleus modulate the subthreshold oscillations, and consequently, the response properties of olivary neurons. A considerable amount of indirect evidence indicates that the occurrence of oscillations corresponds to states of increased responsiveness of the neurons to peripheral stimulation. The sensory filtering role of the inferior olivary nucleus invites comparison between the cerebellum and cerebellar-like structures. This comparison sheds important light on the function of the cerebellum.

Afferent Pathways↗