Kevin D. Alloway

Quantitative measurements of receptive field changes during antagonism of GABAergic transmission in primary somatosensory cortex of cats

SummaryIn cortical area 3b of cats, responses of 76 single neurons to punctate indentations were recorded before and during iontophoretic administration of bicuculline methiodide (BMI), a GABAergic antagonist, at levels that did not affect spontaneous activity. Constant amplitude indentations were applied to selected sites along distalproximal and radial-ulnar axes that intersected the most sensitive area in the receptive field. Profiles of response magnitudes were used to measure receptive field dimensions before and during antagonism of GABAergic inhibition. Blockade of GABAergic transmission caused receptive field dimensions of 48 rapidly-adapting neurons to increase an average 141%, or nearly 2.5 times their original size. Analysis of the spatial distribution of inhibition indicated that in-field inhibition was larger than surround inhibition. During BMI administration, response latency was significantly longer for response elicited from the expanded territory than for responses elicited from within the original receptive field, suggesting that receptive field expansion might be mediated by multisynaptic intracortical connections. The magnitude of receptive field expansion was independent of receptive field size or peripheral location. In a substantial number of neurons, however, BMI produced asymmetric expansions that extended only in the proximal direction. For 9 slowly-adapting neurons, BMI produced measureable increases in receptive field dimensions, but these changes were significantly smaller than the changes in rapidly-adapting neurons.

Differential effects of GABA and bicuculline on rapidly- and slowly-adapting neurons in primary somatosensory cortex of primates

SummaryIn cortical area 3b of monkeys, responses of 71 single neurons to controlled indentations of glabrous skin were recorded before and during iontophoretic application of GABA and bicuculline methiodide (BMI), a GABA receptor antagonist. Constant amplitude indentations were applied to selected sites within the receptive fields of neurons representing the glabrous skin on the digits and palm. Profiles of response magnitudes across stimulation sites were used to quantify receptive field dimensions before and during antagonism of GABAergic inhibition. During administration of BMI, the receptive fields of 26 rapidly-adapting neurons were increased by 3–4 times their original size. Response latencies were substantially longer in the region of expansion than in the original receptive field, suggesting that expansion might be mediated by intracortical connections. The expansion of RFs onto adjacent digits after blockade of GABAergic inhibition suggests that somatotopic reorganization following digit amputations may be subserved by existing excitatory connections. The responses of slowly-adapting neurons were separated into two components, a “dynamic” response corresponding to activity elicited by the initial indenting ramp and a “static” response produced by the sustained indentation. Among 8 slowly-adapting neurons tested with BMI, the receptive fields of the dynamic response component increased to an extent that was similar to the change produced in rapidly-adapting neurons. By contrast, the static response component was rarely altered by BMI. Comparison of the responses to administration of GABA revealed that only 12 of 27 slowly-adapting neurons were inhibited in a dose-dependent manner, whereas 37 of 44 rapidly-adapting neurons exhibited significant reduction of responses in the presence of GABA. Hypotheses are proposed to explain the differential effect of BMI and GABA on slowly- and rapidly-adapting cortical neurons.

Simultaneous electrochemical and unit recording measurements: Characterization of the effects of d-amphetamine and ascorbic acid on neostriatal neurons

Abstract Simultaneous electrochemical measurements and recordings of single-unit activity were obtained from the neostriatum of immobilized, locally anesthetized rats. Electrical cross-talk between the two systems was minimized by the use of carbon-fiber voltammetric electrodes, which generate very small currents during electrolysis, and by the careful isolation of the recording apparatus. An intraperitoneal (i.p.) injection of 2.5 mg/kg d -amphetamine ( d -AMPH) typically inhibited unit activity and produced a corresponding mirror-image increase in oxidation current. Both the depression of firing rate and the elevated electrochemical signal were maximal approximately 25 min after d -AMPH administration. In contrast, both unit activity and oxidation current were elevated after administration of 7.5 mg/kg d -AMPH with the maximum change in firing rate occurring significantly sooner than the peak electrochemical response. In view of evidence that the d -AMPH-induced voltammetric signal is similar to that for ascorbic acid (AA), but not dopamine (DA), a separate group of 12 animals received 1000 mg/kg AA (i.p.). In all cases, AA increased the electrochemical signal and in 7 animals this response was accompanied by an increase in firing rate. Our results, which demonstrate the feasibility of combining in vivo electrochemistry with single-unit electrophysiology, suggest that a d -AMPH-induced release of DA cannot completely explain the dose-dependent biphasic shift in neuronal activity produced by this drug in the neostriatum. Moreover, AA appears to be an effective modulator of neostriatal activity.

Organization of corticostriatal projections from the vibrissal representations in the primary motor and somatosensory cortical areas of rodents

To characterize corticostriatal projections from rodent sensorimotor cortex, the anterograde tracers biotinylated dextran amine (BDA) and fluororuby (FR) were injected into the whisker representations of the primary motor (MI) and somatosensory (SI) cortices. Reconstructions of labeled terminals and their beaded varicosities in the neostriatum and thalamus were analyzed quantitatively to determine the degree of labeled overlap in both of these subcortical structures. Corticostriatal projections from the vibrissal representation in MI were more extensive than corresponding projections from SI. Both cortical areas sent dense projections to the dorsolateral neostriatum, but the MI vibrissal representation also projected to regions located more rostrally and medially. Despite these differences, both MI and SI projected to overlapping parts of the dorsolateral neostriatum. Tracer injections in both cortical areas also produced dense anterograde and retrograde labeling in the medial sector of the posterior complex of the thalamus (POm). Because POm is somatotopically organized and has reciprocal connections with both SI and MI cortices, the amount of labeled overlap in POm was used to indicate whether the tracers were injected into corresponding whisker representations of MI and SI. We found that the proportion of labeled overlap in the neostriatum was highly correlated with the amount of labeled overlap in POm. These results indicate that the rodent neostriatum receives convergent projections from corresponding regions in MI and SI cortex. Furthermore, the thalamocortical projections of the POm indicate that it may modulate corticostriatal outputs from corresponding representations in MI and SI. J. Comp. Neurol. 439:87–103, 2001.

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. J. Comp. Neurol. 498:624–636, 2006.

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. J. Comp. Neurol. 466:525–544, 2003.

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. J. Comp. Neurol. 488:82–100, 2005.

Functional Specificity of Claustrum Connections in the Rat: Interhemispheric Communication between Specific Parts of Motor Cortex

Recent evidence indicates that the rat claustrum interconnects the motor cortical areas in both hemispheres. To elucidate the functional specificity of the interhemispheric connections between the claustrum and primary motor (MI) cortex, anterograde tracer injections in specific parts of MI were paired with retrograde tracer injections in homotopic sites of the opposite hemisphere. In addition to injecting the MI forepaw (Fp) region in both hemispheres, we injected the region associated with whisker retractions (Re) and the more caudal rhythmic whisking (RW) region. While the MI-Fp region has few connections with the claustrum of either hemisphere, both whisker regions project to the contralateral claustrum, with those from the MI-RW region being denser and more extensive than those originating from the MI-Re region. Retrograde tracer injections in the MI-RW region produced more labeled neurons in the ipsilateral claustrum than retrograde tracer injections in the MI-Re. Consistent with these patterns, the overlap of labeled terminals and soma in the claustrum was greatest when both tracers were injected into the MI-RW region. When retrograde tracers were injected into the claustrum, the highest density of labeled neurons in MI appeared in the contralateral RW region. Tracer injections in the claustrum also revealed hundreds of labeled neurons throughout its rostrocaudal extent, thereby establishing the presence of long-range intraclaustral connections. These results indicate that the intrinsic and extrinsic connections of the rat claustrum are structured for rapid, interhemispheric transmission of information needed for bilateral coordination of the MI regions that regulate whisker movements.

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. J. Comp. Neurol. 480:299–309, 2004.

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. J. Comp. Neurol. 499:33–48, 2006.