Biomedical subjects

Kevin D Alloway

Publications and source records attributed to Kevin D Alloway.

12 recordsLinked to original sources

PubMed2006

Topography of cortical projections to the dorsolateral neostriatum in rats: multiple overlapping sensorimotor pathways.

In rodents, the whisker representation in primary somatosensory (SI) cortex projects to the dorsolateral neostriatum, but the location of these projections has never been characterized with respect to layer IV barrels and their intervening septa. To address this issue, we injected a retrograde tracer into the dorsolateral neostriatum and then reconstructed the location of the labeled corticostriatal neurons with respect to the cytochrome oxidase (CO)-labeled barrels in SI. When the tracer was restricted to a small focal site in the neostriatum, the retrogradely labeled neurons formed elongated strips that were parallel to the curvilinear orientation of layer IV barrel rows. After larger tracer injections, labeled neurons were distributed uniformly across layer V and were aligned with both the barrel and septal compartments. Labeled projections from the contralateral SI barrel cortex, however, were much fewer in number and were disproportionately associated with the septal compartments. A comparison of the labeling patterns in the ipsilateral and contralateral hemispheres revealed symmetric, mirror-image distributions that extended across primary motor cortex (MI) and multiple somatosensory cortical regions, including the secondary somatosensory (SII) cortex, the parietal ventral (PV) and parietal rhinal (PR) areas, and the posteromedial (PM) region. Examination of the thalamus revealed labeled neurons in the intralaminar nuclei, in the medial part of the posterior nucleus (POm), and in the ventrobasal complex. These results indicate that the dorsolateral neostriatum integrates sensorimotor information from multiple sensorimotor representations in the thalamus and cortex.

Animals↗

PubMed2006

Differential origin of projections from SI barrel cortex to the whisker representations in SII and MI.

We have previously shown that projections from SI barrel cortex to the MI whisker representation originate primarily from columns of neurons that are aligned with the layer IV septa. SI barrel cortex also projects to SII cortex, but the origin of these projections has not been characterized with respect to the barrel and septal compartments. To address this issue, we injected retrograde tracers into the SII whisker representation and then reconstructed the location of the labeled neurons in SI with respect to the layer IV barrels. In some animals, two different tracers were injected into the whisker representations of SII and MI to detect double-labeled neurons that would indicate that some SI neurons project to both of these cortical areas. We found that the projections to SII cortex originate from sites that are uniformly distributed throughout the extragranular layers of barrel cortex. In cases in which different tracers were injected in SII and MI, double-labeled neurons appeared above and below the layer IV septal compartment and at sites aligned with the boundaries of the layer IV barrels. To the extent that the columns of neurons aligned with the barrel and septal compartments represent functionally distinct circuits, these results indicate that SII receives information from both circuits, whereas MI receives inputs primarily from the septal circuits.

Amidines↗

PubMed2005

Intercolumnar synchronization of neuronal activity in rat barrel cortex during patterned airjet stimulation: a laminar analysis.

We used cross-correlation analysis to characterize the incidence and strength of stimulus-induced neuronal synchronization in different layers of SI barrel cortex and as a function of neuronal location in different barrel columns. To reduce the possibility of evoking responses that were coordinated by simultaneous whisker movements, multiple whiskers were sequentially stimulated with airjets that moved back-and-forth across the peripheral whisker pad. From a sample of 627 neurons, we characterized 1,182 neuron pairs and found that 687 (58.1%) of these displayed significant peaks of synchronized activity that exceeded the 99.9% confidence limits. Whereas 88% of the infragranular neuron pairs were synchronized during whisker stimulation, only 30% of the neuron pairs in the granular or supragranular layers displayed synchronized responses. The strength of synchronization, as measured by the correlation coefficient, was significantly higher in the infragranular layers than in the other layers. These results indicate that synchronized outputs from the infragranular layers do not depend on synchronized inputs from the upper cortical layers. We also found that synchronization varies with the spatial configuration of the neurons and is strongest for neuron pairs residing in the same row. Given the dense local projections between neighboring barrel columns in the same row, our results indicate that neuronal synchronization is greatest when stimuli simultaneously activate those peripheral receptors whose cortical representations are most densely interconnected. Finally, we compared the present results with synchronized responses in somatosensory (SI) barrel cortex that were evoked by controlled, pulsatile whisker movements in a previous study. We conclude that highly-controlled whisker stimulation increases stimulus coordination and may exaggerate the incidence and strength of synchronization among neurons in the granular or supragranular layers.

Action Potentials↗

PubMed2005

Functional circuits mediating sensorimotor integration: quantitative comparisons of projections from rodent barrel cortex to primary motor cortex, neostriatum, superior colliculus, and the pons.

Motor performance depends on somatosensory feedback, and consistent with this finding, primary somatosensory (SI) cortex projects to several regions involved in motor control. Although the pathways mediating sensorimotor integration are known, few studies have compared their projection patterns. Therefore, in each animal, we injected two anterograde tracers into SI barrel cortex and compared the relative density and spatial extent of the labeled projections to the primary motor (MI) cortex, neostriatum, superior colliculus, and basal pons. Quantitative analysis revealed that these projections terminated most extensively in the neostriatum, to a lesser extent in MI cortex, and innervated the least amount of neuropil in the superior colliculus and pontine nuclei. Tracer overlap in the pontine nuclei was significantly higher than in the other three brains regions, and was strongly correlated with overlap in the superior colliculus, presumably because some projections to these two brain regions represent collaterals of the same neurons. The density of labeled varicosities was highest in the pons and lowest in MI. As a proportion of total labeling, densely packed clusters of labeled terminals were most prevalent in the pons, less prevalent in neostriatum and superior colliculus, and least prevalent in MI cortex. These results are consistent with physiological evidence indicating strong coherence between SI barrel cortex and the cerebellum during whisking behavior.

Animals↗

PubMed2004

Septal columns in rodent barrel cortex: functional circuits for modulating whisking behavior.

In rodents, each mystacial whisker is represented in the granular layer of primary somatosensory (SI) cortex by a compact cluster of cells known as a barrel, and barrels are separated from each other by domains that are called septa. Vertical columns of neurons aligned with each barrel act as a functional assembly to process information from a "principal" whisker, but a functional role has not been identified for vertical columns of neurons that are aligned with the septa. To determine whether these septal columns provide the main source of projections to primary motor (MI) cortex, we placed retrograde tracers in MI cortex and analyzed the location of the retrogradely labeled neurons with respect to the septal and barrel compartments of SI barrel cortex. In cases in which SI barrel cortex was sectioned tangentially, retrogradely labeled neurons in the extragranular layers of SI were plotted and superimposed onto reconstructions of the layer IV barrel field. In each of these cases, most labeled neurons were located above or below the septal regions of layer IV. When SI barrel cortex was sectioned coronally, we observed multiple columns of labeled SI neurons that were vertically aligned with the septal zones of layer IV. These results indicate that columns of neurons that are vertically aligned with the septa, or septal columns, are functionally linked by virtue of their projections to MI cortex. We hypothesize that these septal columns represent an interconnected and functionally distinct circuit that transmits information to MI and other brain regions involved in motor control.

Animals↗

PubMed2004

Three-dimensional topography of corticopontine projections from rat sensorimotor cortex: comparisons with corticostriatal projections reveal diverse integrative organization.

The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are considered to represent anatomically segregated channels for information originating in different cortical areas. A capacity for integrating unique combinations of cortical inputs has been well documented in the basal ganglia circuits but is largely undefined in the precerebellar circuits. To compare and quantify the amount of overlap that occurs in the first link of the cortico-ponto-cerebellar pathway, a dual tracing approach was used to map the spatial relationship between projections originating from the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), and the primary motor cortex (MI). The anterograde tracers biotinylated dextran amine and Fluoro-Ruby were injected into homologous whisker representations of either SI and SII, or SI and MI. The ensuing pontine labeling patterns were analyzed using a computerized three-dimensional reconstruction approach. The results demonstrate that whisker-related projections from SI and MI are largely segregated. At some locations, the two projections are adjoining and partly overlapping. Furthermore, SI contributes significantly more corticopontine projections than MI. By comparison, projections from corresponding representations in SI and SII terminate in similar parts of the pontine nuclei and display considerable amounts of spatial overlap. Finally, comparison of corticopontine and corticostriatal projections in the same experimental animals reveals that SI-SII overlap is significantly larger in the pontine nuclei than in the neostriatum. These structural differences indicate a larger capacity for integration of information within the same sensory modality in the pontocerebellar system compared to the basal ganglia.

Animals↗

PubMed2004

Stimulus-induced intercolumnar synchronization of neuronal activity in rat barrel cortex: a laminar analysis.

We used cross-correlation analysis to characterize the coordination of stimulus-induced neuronal activity in the primary somatosensory barrel cortex of isoflurane-anesthetized rats. On each trial, multiple whiskers were simultaneously deflected at frequencies that corresponded to 2, 5, 8, or 11 Hz. Among 476 neuron pairs that we examined, 342 (71.8%) displayed significant peaks of synchronized activity that exceeded the 99.9% confidence limits. The incidence and strength of these functional associations varied across different cortical layers. Only 52.9% of neuron pairs in layer IV displayed synchronized responses, whereas 84.1% of the infragranular neuron pairs were synchronized during whisker stimulation. Neuronal synchronization was strongest in the infragranular layers, weakest in layer IV, and varied according to the columnar configuration of the neuron pairs. Thus correlation coefficients were largest for neuron pairs in the same whisker barrel row but were smallest for neurons in different rows and arcs. Spontaneous activity in the infragranular layers was also synchronized to a greater degree than in the other layers. Although infragranular neuron pairs displayed similar amounts of synchronization in response to each stimulus frequency, granular and supragranular neurons were synchronized mainly during stimulation at 2 or 5 Hz. These results are consistent with previous studies indicating that infragranular neurons have intrinsic properties that facilitate synchronized activity, and they suggest that neuronal synchronization plays an important role in transmitting sensory information to other cortical or subcortical brain regions.

Action Potentials↗

PubMed2003

Sensorimotor corticocortical projections from rat barrel cortex have an anisotropic organization that facilitates integration of inputs from whiskers in the same row.

We used a dual anterograde-tracing paradigm to characterize the organization of corticocortical projections from primary somatosensory (SI) barrel cortex. In one group of rats, biotinylated dextran amine (BDA) and Fluoro-Ruby (FR) were injected into separate barrel columns that occupied the same row of barrel cortex; in the other group, the tracers were deposited into barrel columns residing in different rows. The labeled corticocortical terminals in the primary motor (MI) and secondary somatosensory (SII) cortices were plotted, and digital reconstructions of these plots were quantitatively analyzed. In all cases, labeled projections from focal tracer deposits in SI barrel cortex terminated in elongated, row-like strips of cortex that corresponded to the whisker representations of the MI or SII cortical areas. When both tracers were injected into separate parts of the same SI barrel row, FR- and BDA-labeled terminals tended to merge into a single strip of labeled MI or SII cortex. By comparison, when the tracers were placed in different SI barrel rows, both MI and SII contained at least two row-like FR- and BDA-labeled strips that formed mirror image representations of the SI injection sites. Quantitative analysis of these labeling patterns revealed three major findings. First, labeled overlap in SII was significantly greater for projections from the same barrel row than for projections from different barrel rows. Second, in the infragranular layers of MI but not in the supragranular layers, labeled overlap was significantly higher for projections from the same SI barrel row. Finally, in all layers of SII and in the infragranular layers of MI, the amount of labeled overlap was proportional to the proximity of the tracer injection sites. These results indicate that SI projections to MI and SII have an anisotropic organization that facilitates the integration of sensory information received from neighboring barrels that represent whiskers in the same row.

Animals↗

PubMed2003

Quantitative comparisons of corticothalamic topography within the ventrobasal complex and the posterior nucleus of the rodent thalamus.

To compare the topographic precision of corticothalamic projections to the ventrobasal (VB) complex and the medial part of the posterior (POm) complex, different anterograde tracers were placed in neighboring parts of the primary (SI) and secondary (SII) somatosensory cortical areas. The location of labeled corticothalamic terminals and their beaded varicosities were plotted, and the digital reconstructions were analyzed quantitatively to determine the extent of overlapping projections from the cortical injection sites. Among animals that received all tracer injections in SI cortex, tracer overlap in the thalamus varied according to the proximity of the cortical injection sites. Regardless of which combination of somatic representations were injected in SI, within each animal the amount of tracer overlap in POm was similar to that observed in VB, and a matched-sample statistical analysis failed to reveal significant differences in the proportion of the labeled regions that contained overlapping projections from the injected cortical sites. Among those animals in which the tracers were injected into the whisker representations of SI and SII, the amount of tracer overlap in the thalamus was not affected by the proximity of the cortical injection sites. Instead, tracer overlap appeared to be related to the degree of somatotopic correspondence. Furthermore, within each of these animals, the amount of tracer overlap in POm was similar to that found in the VB complex. These results indicate that POm has a well-defined topographic organization that is comparable to the degree of topography observed in the VB complex.

Animals↗

PubMed2003

Resiniferatoxin induces paradoxical changes in thermal and mechanical sensitivities in rats: mechanism of action.

Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, has been used as a tool to study the role of capsaicin-sensitive C fibers in pain. Recently, we found that RTX diminished the thermal sensitivity but unexpectedly increased the sensitivity to tactile stimulation in adult rats. In this study, we explored the potential mechanisms involved in RTX-induced changes in somatosensory function. An intraperitoneal injection of 200 microg/kg RTX, but not its vehicle, rapidly produced an increase in the paw withdrawal latency to a heat stimulus. Also, profound tactile allodynia developed in all the RTX-treated rats in 3 weeks. This paradoxical change in thermal and mechanical sensitivities lasted for at least 6 weeks. Electron microscopic examination of the sciatic nerve revealed a loss of unmyelinated fibers and extensive ultrastructural damage of myelinated fibers in RTX-treated rats. Immunofluorescence labeling showed a diminished vanilloid receptor 1 immunoreactivity in dorsal root ganglia neurons and the spinal dorsal horn of RTX-treated rats. Furthermore, two transganglionic tracers, horseradish peroxidase conjugates of cholera toxin B subunit (CTB) and isolectin-B(4) of Bandeiraea simplicifolia (IB(4)), were injected into the opposite sides of the sciatic nerve to trace myelinated and unmyelinated afferent terminations, respectively, in the spinal dorsal horn. In RTX-treated rats, IB(4)-labeled terminals in the dorsal horn were significantly reduced, and CTB-labeled terminals appeared to sprout into lamina II of the spinal dorsal horn. Thus, this study demonstrates that systemic RTX diminishes the thermal pain sensitivity by depletion of unmyelinated afferent neurons. The delayed tactile allodynia induced by RTX is likely attributable to damage to myelinated afferent fibers and their abnormal sprouting in lamina II of the spinal dorsal horn. These data provide new insights into the potential mechanisms of postherpetic neuralgia.

Afferent Pathways↗

PubMed2002

Projections from primary somatosensory cortex to the neostriatum: the role of somatotopic continuity in corticostriatal convergence.

We characterized the organization of corticostriatal projections from rodent primary somatosensory cortex (SI), testing the hypothesis that projections from SI areas representing subcomponents of the forelimb exhibit greater neostriatal overlap than projections from areas representing separate body parts. The anterograde tracers Fluoro-Ruby (FR), Alexa Fluor (AF), and biotinylated dextran amine (BDA) were injected into physiologically identified regions of rat SI. Injection locations were confirmed by examining the SI barrel fields and limb representations in tangential sections processed for cytochrome oxidase (CO). Experimental animals were divided into two groups: one group received multiple tracer injections in neighboring SI regions that represent separate body parts (whiskers, forepaw, and hindpaw); the other group received injections in SI areas that represent different components of the forelimb (forepaw, antebrachium, and brachium). The distribution of labeled terminals and their varicosities in the neostriatum and in the thalamus were plotted and quantitatively analyzed. For most animals, tracer overlap in the thalamus was either minimal or completely absent. In the neostriatum, projections from the whisker, forelimb, and hindlimb representations terminated in regions that rarely overlap with each other, while those originating from different parts of the forelimb representation were more likely to terminate in overlapping parts of the neostriatum. To the extent that neostriatal activation depends on corticostriatal convergence, the corticostriatal projections in the sensorimotor channel appeared to be organized so that neostriatal neurons may signal when multiple components of the same body part are activated simultaneously.

Animals↗

PubMed2002

Pervasive synchronization of local neural networks in the secondary somatosensory cortex of cats during focal cutaneous stimulation.

Extracellular discharges were recorded from 205 neurons in the secondary somatosensory (SII) cortex of isoflurane-anesthetized cats. Cross-correlation analysis was used to characterize the temporal coordination of SII neurons recorded during cutaneous stimulation with a focal air jet that moved back-and-forth across the distal forelimb. Over two-thirds of the recorded neuron pairs ( n=357) displayed significant levels of synchronized activity during one or both directions of air-jet movement. The probability of detecting correlated activity varied according to the distance separating the neurons. Whereas synchronized responses were observed in 82.3% of the pairs in which the neurons were separated by 200-300 micro m, the incidence of synchronization declined to 52.3% for neurons that were separated by 600-800 micro m. The distance between neurons also had a significant effect on the temporal precision of correlated activity. For neurons that were separated by 200-300 micro m, synchronized responses in the cross-correlograms (CCGs) were characterized by narrow (0.5-1.0 ms) peaks at time zero. For SII neurons that were more widely separated, the peak half-widths were substantially broader and more likely to be displaced from time zero. Analysis of directional sensitivity indicated that only 14.2% of the correlated neurons displayed a directional preference for synchronized activity. By comparison, 63.4% of the neurons displayed a directional preference in their discharge rate. These results indicate that stimulus-induced synchronization is a prominent feature among local populations of SII neurons, but synchronization does not appear to play a critical role in coding the direction of stimulus movement. A comparison of these results with those obtained from similar experiments conducted in primary somatosensory (SI) cortex indicates that neuronal synchronization is more likely in SII cortex. This finding is discussed with respect to the known functional differences between the SI and SII cortical areas.

Action Potentials↗