I know the pain you feel-how the human brain's default mode predicts our resonance to another's suffering.

Introspective and self-referential in nature, the human brain's default mode network (DMN) is presumed to influence our behavior in response to the environment in predictive manner [Raichle ME, Gusnard DA (2005) J Comp Neurol 493:167-176; Bar M (2009) Philos Trans R Soc Lond B Biol Sci 364:1235-1243]. In the current study, we hypothesize that the strength of DMN-connectivity contributes to distinct introspective psychological processes in every-day social life such as the intuitive understanding of other people through inner representation of their affective states -e. g. his or her pain. 19 healthy individuals underwent functional MRI scanning, which consisted of a resting-state-scan followed by the presentation of visual stimuli depicting human limbs in painful and non-painful situations. After scanning, participants were asked to evaluate the stimuli in terms of pain intensity perceived from the first person perspective. Independent component analysis (ICA) demonstrated that higher integration of the left medial orbitofrontal cortex (BA 32) into the anterior default mode network (aDMN) was associated with higher post-scan pain ratings. Furthermore, the exposition to the "Pain"-pictures led to relative increases of aDMN-activity compared to "No Pain"-stimuli which were also correlated with the subjective pain intensity. The behaviorally predictive functional architecture during a task-free period supports the notion that the DMN serves as a "memory of the future" [Ingvar DH (1985) Hum Neurobiol 4:127-136] in terms of a neuronal cache, storing "a priori scripts," which are recalled to deal efficiently with upcoming environmental events. In addition, our results suggest that an individual predisposition to identify oneself with another's pain influences the automatic response of the DMN during the observation of painful situations.

Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test.

PURPOSE: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re-investigate this topic with a larger N than has heretofore been used. METHODS: The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated. RESULTS: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA. CONCLUSIONS: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects.

Intracortical pathway involving dysgranular cortex conveys hindlimb inputs to S-I forelimb-stump representation of neonatally amputated rats.

Reorganization of the primary somatosensory cortex (S-I) forelimb-stump representation of rats that sustained neonatal forelimb removal is characterized by the expression of hindlimb inputs that are revealed when cortical GABA receptors are pharmacologically blocked. Recent work has shown that the majority of these inputs are transmitted from the S-I hindlimb representation to the forelimb-stump field via an, as yet, unidentified pathway between these regions. In this study, we tested the possibility that hindlimb inputs to the S-I forelimb-stump representation of neonatally amputated rats are conveyed through an intracortical pathway between the S-I hindlimb and forelimb-stump representations that involves the intervening dysgranular cortex by transiently inactivating this area and evaluating the effect on hindlimb expression in the S-I forelimb-stump representation during GABA receptor blockade. Of 332 S-I forelimb-stump recording sites from six neonatally amputated rats, 68.3% expressed hindlimb inputs during GABA receptor blockade. Inactivation of dysgranular cortex with cobalt chloride (CoCl(2)) resulted in a significant decrease in the number of hindlimb responsive sites (9.5%, P < 0.001 vs. cortex during GABA receptor blockade before CoCl(2) treatment). Results were also compiled from S-I forelimb recording sites from three normal rats: 14.1% of 136 sites were responsive to the hindlimb during GABA receptor blockade, and all of these responses were abolished during inactivation of dysgranular cortex with CoCl(2) (P < 0.05). These results indicate that the S-I hindlimb representation transmits inputs to the forelimb-stump field of neonatally amputated rats through a polysynaptic intracortical pathway involving dysgranular cortex. Furthermore the findings from normal rats suggest that this pathway might reflect the amplification of a neuronal circuit normally present between the two representations.

Pervasive emotion recognition deficit common to alexithymia and the repressive coping style.

OBJECTIVE: Previous research has demonstrated a deficit in the ability to recognize emotions in alexithymic individuals. The repressive coping style is thought to preferentially impair the detection of unpleasant compared with pleasant emotions, and the degree of deficit is typically thought to be less severe than in alexithymia. We compared emotion recognition ability in both individuals with alexithymia and those with the repressive coping style. METHODS: Three hundred seventy-nine subjects completed the 20-item Toronto Alexithymia Scale, the Levels of Emotional Awareness Scale, the Marlowe-Crowne Scale (a measure of repressive defensiveness), the Bendig Short Form of the Taylor Manifest Anxiety Scale, and the Perception of Affect Task. The Perception of Affect Task consists of four 35-item emotion recognition subtasks: matching sentences and words, faces and words, sentences and faces, and faces and photographs of scenes. The stimuli in each subtask consist of seven emotions (happiness, sadness, anger, fear, disgust, surprise, and neutral) depicted five times each. Recognition accuracy results were collapsed across subtasks within each emotion category. RESULTS: Highly alexithymic subjects (for all, p<.01) and those with low emotional awareness (for all, p<.001) were consistently less accurate in emotion recognition in all seven categories. Highly defensive subjects (including repressors) were less accurate in the detection of anger, sadness, fear, and happiness (for all, p<.05). Furthermore, scores on the Levels of Emotional Awareness Scale accounted for significantly more variance in performance on the Perception of Affect Task than scores on the Marlowe-Crowne Scale (p<.01). CONCLUSIONS: The results indicate that alexithymia and the repressive coping style are each associated with impairments in the recognition of both pleasant and unpleasant emotions and that the two styles of emotional self-regulation differ more in the magnitude than in the quality of these impairments.

Selective facilitation of the serotonin(1B) receptor causes disorganization of thalamic afferents and barrels in somatosensory cortex of rat.

Alteration of serotonin (5-HT) levels influences developing thalamocortical afferents (TCAs) in primary somatosensory cortex (SI) of rats and mice. The 5-HT(1B) receptor, present on TCAs during the first postnatal week, may be involved in these effects. The present study asked whether administration of 5-nonyloxytriptamine (NNT), a selective 5-HT(1B) receptor agonist, affects TCA organization in rat SI. Littermates were injected five times daily (5x/day), with either 0.1 mg/kg NNT or vehicle from birth to postnatal day 6 (P-6). Animals were killed on P-6, and their brains were processed for high-performance liquid chromatography (HPLC), cytochrome oxidase (CO) histochemistry, cresyl violet, or demonstration of TCAs by placement of 1,1'-dioctadecyl-3,3,3'' 3'-tetra-methylindocarbocyanine perchlorate (Di-I) on thalamocortical radiations. At P-6, NNT treatment decreased 5-HT levels slightly compared with controls, although this difference was not statistically significant. In NNT-treated rats, the Di-I-labeled vibrissae-related pattern showed a range of effects, from fusion of patches related to mystacial vibrissae in treated animals to a less distinct vibrissae-related pattern in SI barrelfield compared with controls. Staining for CO and Nissl stain in layer IV of SI showed a similar range of abnormalities. These results indicate that the agonist action of NNT at the 5-HT(1B) receptor causes TCA disorganization in rat barrel field cortex in the absence of elevated 5-HT.

Suppression of hindlimb inputs to S-I forelimb-stump representation of rats with neonatal forelimb removal: GABA receptor blockade and single-cell responses.

Neonatal forelimb removal in rats results in the development of inappropriate hindlimb inputs in the forelimb-stump representation of primary somatosensory cortex (S-I) that are revealed when GABA(A) and GABA(B) receptor activity are blocked. Experiments carried out to date have not made clear what information is being suppressed at the level of individual neurons. In this study, three potential ways in which GABA-mediated inhibition could suppress hindlimb expression in the S-I stump representation were evaluated: silencing S-I neurons with dual stump and hindlimb receptive fields, silencing neurons with receptive fields restricted to the hindlimb alone, and/or selective silencing of hindlimb inputs to neurons that normally express a stump receptive field only. These possibilities were tested using single-unit recording techniques to evaluate the receptive fields of S-I forelimb-stump neurons before, during, and after blockade of GABA receptors with bicuculline methiodide (for GABA(A)) and saclofen (for GABA(B)). Recordings were also made from normal rats for comparison. Of 92 neurons recorded from the S-I stump representation of neonatally amputated rats, only 2.2% had receptive fields that included the hindlimb prior to GABA receptor blockade. During GABA receptor blockade, 54.3% of these cells became responsive to the hindlimb, and in all but two cases, these same neurons also expressed a stump receptive field. Most of these cells (82.0%) expressed only stump receptive fields prior to GABA receptor blockade. In 71 neurons recorded from normal rats, only 5 became responsive to the hindlimb during GABA receptor blockade. GABA receptor blockade of cortical neurons, in both normal and neonatally amputated rats, resulted in significant enlargements of receptive fields as well as the emergence of receptive fields for neurons that were normally unresponsive. GABA receptor blockade also resulted in increases in both the spontaneous activity and response magnitudes of these neurons. These data support the conclusion that GABA mechanisms generally act to specifically suppress hindlimb inputs to S-I forelimb-stump neurons that normally express a receptive field on the forelimb stump only.

A model of neurovisceral integration in emotion regulation and dysregulation.

In the present paper we present the outlines of a model that integrates autonomic, attentional, and affective systems into a functional and structural network that may help to guide us in our understanding of emotion regulation and dysregulation. We will emphasize the relationship between attentional regulation and affective processes and propose a group of underlying physiological systems that serve to integrate these functions in the service of self-regulation and adaptability of the organism. We will attempt to place this network in the context of dynamical systems models which involve feedback and feedforward circuits with special attention to negative feedback mechanisms, inhibitory processes, and their role in response selection. From a systems perspective, inhibitory processes can be viewed as negative feedback circuits that allow for the interruption of ongoing behavior and the re-deployment of resources to other tasks. When these negative feedback mechanisms are compromised, positive feedback loops may develop as a result (of dis-inhibition). From this perspective, the relative sympathetic activation seen in anxiety disorders may represent dis-inhibition due to faulty inhibitory mechanisms.

Common effects of emotional valence, arousal and attention on neural activation during visual processing of pictures.

Emotion and attention heighten sensitivity to visual cues. How neural activation patterns associated with emotion change as a function of the availability of attentional resources is unknown. We used positron emission tomography (PET) and 15O-water to measure brain activity in male volunteers while they viewed emotional picture sets that could be classified according to valence or arousal. Subjects simultaneously performed a distraction task that manipulated the availability of attentional resources. Twelve scan conditions were generated in a 3 x 2 x 2 factorial design involving three levels of valence (pleasant, unpleasant and neutral), two levels of arousal and two levels of attention (low and high distraction). Extrastriate visual cortical and anterior temporal areas were independently activated by emotional valence, arousal and attention. Common areas of activation derived from a conjunction analysis of these separate activations revealed extensive areas of activation in extrastriate visual cortex with a focus in right BA18 (12, -88, -2) (Z=5.73, P < 0.001 corrected) and right anterior temporal cortex BA38 (42, 14, -30) (Z=4.03, P < 0.05 corrected). These findings support an hypothesis that emotion and attention modulate both early and late stages of visual processing.

Source of inappropriate receptive fields in cortical somatotopic maps from rats that sustained neonatal forelimb removal.

Previously this laboratory demonstrated that forelimb removal at birth in rats results in the invasion of the cuneate nucleus by sciatic nerve axons and the development of cuneothalamic cells with receptive fields that include both the forelimb-stump and the hindlimb. However, unit-cluster recordings from primary somatosensory cortex (SI) of these animals revealed few sites in the forelimb-stump representation where responses to hindlimb stimulation also could be recorded. Recently we reported that hindlimb inputs to the SI forelimb-stump representation are suppressed functionally in neonatally amputated rats and that GABAergic inhibition is involved in this process. The present study was undertaken to assess the role that intracortical projections from the SI hindlimb representation may play in the functional reorganization of the SI forelimb-stump field in these animals. The SI forelimb-stump representation was mapped during gamma-aminobutyric acid (GABA)-receptor blockade, both before and after electrolytic destruction of the SI hindlimb representation. Analysis of eight amputated rats showed that 75.8% of 264 stump recording sites possessed hindlimb receptive fields before destruction of the SI hindlimb. After the lesions, significantly fewer sites (13.2% of 197) were responsive to hindlimb stimulation (P < 0.0001). Electrolytic destruction of the SI lower-jaw representation in four additional control rats with neonatal forelimb amputation did not significantly reduce the percentage of hindlimb-responsive sites in the SI stump field during GABA-receptor blockade (P = 0.98). Similar results were obtained from three manipulated rats in which the SI hindlimb representation was silenced temporarily with a local cobalt chloride injection. Analysis of response latencies to sciatic nerve stimulation in the hindlimb and forelimb-stump representations suggested that the intracortical pathway(s) mediating the hindlimb responses in the forelimb-stump field may be polysynaptic. The mean latency to sciatic nerve stimulation at responsive sites in the GABA-receptor blocked SI stump representation of neonatally amputated rats was significantly longer than that for recording sites in the hindlimb representation [26.3 +/- 8.1 (SD) ms vs. 10.8 +/- 2.4 ms, respectively, P < 0.0001]. These results suggest that hindlimb input to the SI forelimb-stump representation detected in GABA-blocked cortices of neonatally forelimb amputated rats originates primarily from the SI hindlimb representation.

Effect of activity blockade on changes in vibrissae-related patterns in the rat's primary somatosensory cortex induced by serotonin depletion.

Depletion of cortical serotonin (5-HT) during development results in a decrease in the size of the patches of thalamocortical afferents representing the mystacial vibrissae in lamina IV of the primary somatosensory cortex (SI). We previously suggested that this change may be due to a reduction in 5-HT-induced suppression of thalamocortical activity in these animals. The present experiments directly tested the role that modulation of activity may play in the morphologic changes observed after reducing cortical 5-HT concentrations. Serotonin was depleted from the cortex by systemic administration of 5,7-dihydroxytryptamine (5,7-DHT, 100 mg/kg) on the day of birth in animals that also had either tetrodotoxin (TTX)-impregnated or control implants placed unilaterally over the developing SI on this day. Other rat pups were treated with TTX-impregnated or control implants alone. Administration of 5,7-DHT reduced cortical serotonin levels and this effect was not significantly modified by the presence of either control or TTX-impregnated cortical implants. Administration of 5,7-DHT reduced the cross-sectional area of the cortical patches, demonstrated by acetylcholinesterase, corresponding to the vibrissae by 19.9% (P < 0.05). A similar reduction was observed in the animals treated with both 5,7-DHT and TTX-impregnated implants. Treatment with TTX-impregnated implants alone resulted in a 3.1% increase in patch size (P > 0.05). None of the treatments significantly altered the overall area of the part of SI devoted to the representation of the long mystacial vibrissae. These results suggest that the effects of 5-HT depletion on the size of the cortical patches representing the long vibrissae are independent of activity that can be blocked by administration of TTX.

Sociodemographic correlates of alexithymia.

The association between alexithymia and sociodemographic variables is not well understood. Previous studies using the current 20-item and previous 26-item versions of the Toronto Alexithymia Scale (TAS) have shown inconsistent associations with age, sex, socioeconomic status, and years of education. We tested 380 subjects from the community stratified equally across sex, five age groups, and three socioeconomic classes. In addition to the TAS-20, we also administered the Levels of Emotional Awareness Scale (LEAS), a behavioral measure of the ability to be aware of and represent emotions in words, a core component of alexithymia. The TAS-20 and LEAS were each correlated with age, sex, socioeconomic status (SES), and years of education (P < .01) in the same direction and to approximately the same degree. Alexithymia (or low emotional awareness) is associated with older age, male sex, lower SES, and fewer years of education. The TAS-20 and LEAS are only slightly correlated (r = -.19, n = 380, P < .001), but their correlation is largely accounted for by their shared variance with these demographic variables. The convergence of findings with these two quite different measures and the nature of their overlap support the validity of these associations between alexithymia and sociodemographic variables.

Thalamocortical and intracortical projections to the forelimb-stump SI representation of rats that sustained neonatal forelimb removal.

We previously reported the abnormal expression of hindlimb receptive fields in the stump representation of the primary somatosensory cortex (SI) in rats that sustained neonatal forelimb removal when cortical gamma-aminobutyric acid (GABA) receptors were pharmacologically blocked (Lane et al. [1997] J. Neurophysiol. 77:2723-2735). In this study, we attempted to identify the substrate for this functional modification. Three potential substrates were examined: 1) changes in intracortical connections within SI; 2) alterations in the projection pattern of thalamocortical afferents from the ventroposterior lateral (VPL) nucleus to SI; and 3) changes in the receptive fields of thalamocortical neurons. We used biotinylated dextran amine and Phaseolus vulgaris leucoagglutinin to examine the intracortical projections associated with the stump and hindlimb representations of SI. True Blue and Diamidino Yellow were used to study the organization of the VPL projections to SI. Finally, single-unit recordings from VPL neurons were made to examine the functional organization of this nucleus in neonatally amputated adult rats. Tracer studies demonstrated no significant change in the intracortical connections or VPL projections associated with the stump and hindlimb SI in neonatally amputated rats. Recordings from VPL of neonatally manipulated rats revealed a small, but significant, population of cells (19.0%) within the stump representation that had dual stump and hindlimb receptive fields. Thus, the data suggest that the functional reorganization observed in SI of neonatally amputated rats may reflect functional alterations occurring in its thalamic inputs.

Neural correlates of levels of emotional awareness. Evidence of an interaction between emotion and attention in the anterior cingulate cortex.

Recent functional imaging studies have begun to identify the neural correlates of emotion in healthy volunteers. However, studies to date have not differentially addressed the brain areas associated with the perception, experience, or expression of emotion during emotional arousal. To explore the neural correlates of emotional experience, we used positron emission tomography (PET) and 15-water to measure cerebral blood flow (CBF) in 12 healthy women during film- and recall-induced emotion and correlated CBF changes attributable to emotion with subjects' scores on the Levels of Emotional Awareness Scale (LEAS), a measure of individual differences in the capacity to experience emotion in a differentiated and complex way. A conjunction analysis revealed that the correlations between LEAS and CBF during film- and recall-induced emotion overlapped significantly (z = 3.74, p < 0. 001) in Brodmann's area 24 of the anterior cingulate cortex (ACC). This finding suggests that individual differences in the ability to accurately detect emotional signals interoceptively or exteroceptively may at least in part be a function of the degree to which the ACC participates in the experiential processing and response to emotion cues. To the extent that this finding is consistent with the functions of the ACC involving attention and response selection, it suggests that this neural correlate of conscious emotional experience is not exclusive to emotion.

Augmentation of serotonin in the developing superior colliculus alters the normal development of the uncrossed retinotectal projection.

A previous study from this laboratory showed that sprouting of serotoninergic axons in the hamster's superior colliculus (SC) induced by a single subcutaneous injection of 5,7-dihydroxytryptamine (5,7-DHT) at birth (postnatal day 0; P-0) resulted in an abnormal terminal distribution of the uncrossed retinotectal projection. The present study provided further evidence to support the role of increased 5-HT levels within the SC in this phenomenon. Slow-release polymer (ELVAX) chips impregnated with serotonin (5-HT) were placed over the SC on either P-1 or P-3, and retinotectal projections were assessed via anterograde transport of horseradish peroxidase when animals reached P > 18. Analysis of ELVAX chips indicated that they released 5-HT in amounts of > or = 1 pmole/hour for at least 12 days. Assessment of the SC of treated hamsters indicated significantly elevated 5-HT concentrations as late as P-12, but not on P-16. Implantation of 5-HT chips, but not control chips, resulted in abnormalities in the uncrossed retinotectal projection similar to those observed in the 5,7-DHT-treated animals. The patches that normally develop in the rostral part of the stratum opticum were not present, and uncrossed axons were distributed densely in this layer and in the lower portion of the stratum griseum superficiale throughout the rostrocaudal and mediolateral extents of the SC. Quantitative analysis of these changes indicated significant differences between the organization of the uncrossed retinotectal projections of 5-HT-treated animals vs. either blank-implant treated or completely untreated animals but not between 5-HT-treated hamsters and animals that received neonatal 5,7-DHT injections. All of these results support the conclusion that increased SC concentrations of 5-HT altered retinotectal development.

Neuroanatomical correlates of pleasant and unpleasant emotion.

Substantial evidence suggests that a key distinction in the classification of human emotion is that between an appetitive motivational system association with positive or pleasant emotion and an aversive motivational system associated with negative or unpleasant emotion. To explore the neural substrates of these two systems, 12 healthy women viewed sets of pictures previously demonstrated to elicit pleasant, unpleasant and neutral emotion, while positron emission tomographic (PET) measurements of regional cerebral blood flow were obtained. Pleasant and unpleasant emotions were each distinguished from neutral emotion conditions by significantly increased cerebral blood flow in the vicinity of the medial prefrontal cortex (Brodmann's area 9), thalamus, hypothalamus and midbrain (P < 0.005). Unpleasant was distinguished from neutral or pleasant emotion by activation of the bilateral occipito-temporal cortex and cerebellum, and left parahippocampal gyrus, hippocampus and amygdala (P < 0.005). Pleasant was also distinguished from neutral but not unpleasant emotion by activation of the head of the left caudate nucleus (P < 0.005). These findings are consistent with those from other recent PET studies of human emotion and demonstrate that there are both common and unique components of the neural networks mediating pleasant and unpleasant emotion in healthy women.

Neuroanatomical correlates of happiness, sadness, and disgust.

OBJECTIVE: Happiness, sadness, and disgust are three emotions that differ in their valence (positive or negative) and associated action tendencies (approach or withdrawal). This study was designed to investigate the neuroanatomical correlates of these discrete emotions. METHOD: Twelve healthy female subjects were studied. Positron emission tomography and [15O]H2O were used to measure regional brain activity. There were 12 conditions per subject: happiness, sadness, and disgust and three control conditions, each induced by film and recall. Emotion and control tasks were alternated throughout. Condition order was pseudo-randomized and counterbalanced across subjects. Analyses focused on brain activity patterns for each emotion when combining film and recall data. RESULTS: Happiness, sadness, and disgust were each associated with increases in activity in the thalamus and medial prefrontal cortex (Brodmann's area 9). These three emotions were also associated with activation of anterior and posterior temporal structures, primarily when induced by film. Recalled sadness was associated with increased activation in the anterior insula. Happiness was distinguished from sadness by greater activity in the vicinity of ventral mesial frontal cortex. CONCLUSIONS: While this study should be considered preliminary, it identifies regions of the brain that participate in happiness, sadness, and disgust, regions that distinguish between positive and negative emotions, and regions that depend on both the elicitor and valence of emotion or their interaction.

Neuroanatomical correlates of externally and internally generated human emotion.

OBJECTIVE: Positron emission tomography was used to investigate the neural substrates of normal human emotional and their dependence on the types of emotional stimulus. METHOD: Twelve healthy female subjects underwent 12 measurements of regional brain activity following the intravenous bolus administration of [15O]H2O as they alternated between emotion-generating and control film and recall tasks. Automated image analysis techniques were used to characterize and compare the increases in regional brain activity associated with the emotional response to complex visual (film) and cognitive (recall) stimuli. RESULTS: Film- and recall-generated emotion were each associated with significantly increased activity in the vicinity of the medial prefrontal cortex and thalamus, suggesting that these regions participate in aspects of emotion that do not depend on the nature of the emotional stimulus. Film-generated emotion was associated with significantly greater increases in activity bilaterally in the occipitotemporparietal cortex, lateral cerebellum, hypothalamus, and a region that includes the anterior temporal cortex, amygdala, and hippocampal formation, suggesting that these regions participate in the emotional response to certain exteroceptive sensory stimuli. Recall-generated sadness was associated with significantly greater increases in activity in the vicinity of the anterior insular cortex, suggesting that this region participates in the emotional response to potentially distressing cognitive or interoceptive sensory stimuli. CONCLUSIONS: While this study should be considered preliminary, it identified brain regions that participate in externally and internally generated human emotion.

Blockade of GABAergic inhibition reveals reordered cortical somatotopic maps in rats that sustained neonatal forelimb removal.

A previous study from this laboratory demonstrated that forelimb removal at birth results in invasion of the cuneate nucleus (CN) by sciatic nerve axons and the development of CN cells including thalamic projection neurons with receptive fields that include both the forelimb stump and the hindlimb. However, recordings from unit clusters in lamina IV of the primary somatosensory cortex (SI) of these animals revealed the presence of only a very few sites in the forelimb stump representation where responses to hindlimb stimulation could also be recorded. In the present study we tested the possibility that input from the hindlimb was suppressed in lamina IV of the cortical stump representation via GABAergic inhibitory mechanisms by mapping this cortical region, applying the gamma-aminobutyric acid-A (GABA(A)) and GABA(B) receptor antagonists bicuculline and phaclofen (50 microM each), and then remapping the same sites. In six neonatally manipulated rats, 15 of 242 sites (6.2%) in the stump representation responded to hindlimb stimulation before GABA receptor blockade and 107 (44.2%) of the same sites responded to stimulation of the hindlimb during blockade (P < 0.05). In six normal adult rats, 7 of 264 sites (2.7%) in the forelimb representation responded to hindlimb stimulation before the application of bicuculline and phaclofen. During GABA receptor blockage, 31 of these sites (11.7%) responded to such stimulation (P < 0.02 vs. the untreated normal cortex and P < 0.01 vs. the neonatally manipulated rats treated with GABA blockers). To specifically test the role of GABA(A) versus GABA(B) receptors in the inhibition of hindlimb input to the SI stump representation in rats that sustained neonatal forelimb removal, either bicuculline or phaclofen alone was applied to SI in nine neonatally manipulated animals. In four rats treated with bicuculline, 12 of 184 sites (6.5%) in the stump representation responded to hindlimb stimulation before treatment and 61 of 184 sites (33.2%) responded to such stimulation during application (P < 0.01). In animals (n = 5) treated with phaclofen, 18 of 251 sites (7.2%) responded to hindlimb stimulation before treatment and 64 of these sites (25.5%) responded to such stimulation during application (P < 0.05). There was no significant difference between the results obtained with bicuculline alone, phaclofen alone, or the two GABA blockers delivered together (P > 0.05). These results indicate that hindlimb input to the portion of SI representing the forelimb stump is functionally suppressed in rats that have sustained neonatal forelimb removal and that GABAergic inhibition, mediated by both GABA(A) and GABA(B) receptors, is involved in this process.

Projection status of calbindin- and parvalbumin-immunoreactive neurons in the superficial layers of the rat's superior colliculus.

Immunocytochemistry and retrograde labeling were used to define the thalamic projections of calbindin- and parvalbumin-containing cells in superficial layers of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8 +/- 2.2% (mean +/- standard deviation) of the calbindin-immunoreactive neurons in the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate nucleus (LGNd) and that 91.3 +/- 4.3% of calbindin-immunoreactive neurons in the stratum opticum (SO) projected to the lateral posterior nucleus (LP). In contrast, only 17.3 +/- 2.5% of parvalbumin-immunoreactive neurons in the SGS were found to project to the LGNd and 16.5 +/- 3.1% of the parvalbumin-immunoreactive SO cells were retrogradely labeled after LP injections. Few of the parvalbumin-immunoreactive neurons in either the SGS (7.2 +/- 2.5%) or the SO (9.2 +/- 2.5%) were GABA positive. The retrograde-labeling results suggest that parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be primarily interneurons or have descending projections, while calbindin-containing cells are primarily thalamic projection neurons. These results are consistent with data from other rodents, but almost exactly the opposite of data that have been reported for the cat for these same populations of SC projection neurons. Such interspecies differences raise questions regarding the functional importance of expressing one calcium-binding protein versus another in a specific neuronal population.