Longitudinal DAT changes measured with [18F]FE-PE2I PET in patients with Parkinson's disease; a validation study.

BACKGROUND: Dopamine transporter (DAT) PET provides higher resolution than DAT SPECT and opportunity for integrated imaging with MRI. The radioligand [18F]FE-PE2I is highly selective for the DAT, and PET measurements with this radioligand have good reliability and repeatability in patients with non-advanced Parkinson's disease. OBJECTIVES: To validate [18F]FE-PE2I PET as measurement tool of longitudinal DAT changes in patients with Parkinson's disease. METHODS: Thirty-seven subjects with Parkinson's disease (Hoehn and Yahr stage < 3) were included in a longitudinal PET study with [18F]FE-PE2I. DAT availability (BPND) in the caudate nucleus, putamen, sensorimotor striatum, and substantia nigra, was estimated with parametric imaging using Logan graphical analysis and cerebellum as reference region. For comparison with DAT-SPECT literature, sample size calculations for disease intervention studies were made. RESULTS: Baseline and follow-up PET data (interval: 2.3 ± 0.5 years) were available for 25 patients (9 females, 16 males). Median age was 64.7 years (range 46-76); symptom duration: 3 years (0.25-14); Hoehn and Yahr stage (H&Y): 1 (1-2). Annualized DAT decline and effect size were: -8.5 ± 6.6 % and 1.08 for caudate nucleus; -7.1 ± 6.1 % and 1.02 for putamen; -8.3 ± 8.5 % and 0.99 for sensorimotor striatum; -0.11 ± 9.3 % and 0.11 for substantia nigra. The estimated minimum sample size needed for a treatment trial using [18F]FE-PE2I PET as imaging marker is 2-3 times lower than is reported in literature on [123I]FP-CIT SPECT. CONCLUSIONS: Longitudinal [18F]FE-PE2I PET measurements in non-advanced PD demonstrate a striatal DAT decline consistent with previous SPECT and PET studies. No obvious changes of DAT availability were observed in the substantia nigra, indicating perhaps slower progression or compensatory changes. The effect sizes were numerically larger than reported in the literature for other DAT radioligands, suggesting that [18F]FE-PE2I might detect smaller DAT changes, and can be well used as progression marker in clinical trials.

Whisking in air: encoding of kinematics by VPM neurons in awake rats.

Rodent whisking behavior generates two types of neural signals: one produced by whisker contact with objects; the other by movements in air. While kinematic signals generated by contact reliably activate neurons at all levels of the trigeminal neuraxis, the extent to which the kinematics of whisking in air are reliably encoded at each level remains unclear. Previously, we showed that the responses of trigeminal ganglion (TG) neurons in awake, head-fixed rats are correlated with whisking kinematic parameters, but that individual neurons may differ substantially in the reliability of their kinematic encoding. Here, we extend that analysis to neurons in the ventral posterior medial (VPM) nucleus. Three possible coding strategies were examined: (1) firing rate across an entire movement; (2) the probability of individual spikes as a function of the instantaneous movement trajectory; and (3) the coherence between spikes and whisking. While VPM neurons were clearly responsive to variations in whisker kinematics during whisking in air, the encoding of whisker kinematics by VPM neurons was less consistent than that of TG neurons. Furthermore, we found that, in VPM as in TG, movement direction is an important determinant of unit responsiveness during whisking in air.

Prenatal Exposure to Famine and Risk for Development of Psychopathology in Adulthood: A Meta-Analysis.

Prenatal famine, resulting in intrauterine malnutrition, impacts offspring psychopathology later in adulthood. In addition, the specific impact of intrauterine malnutrition of different psychopathology differs by the timing of the exposure. Using a meta-analysis, the current study assessed the specific risk of developing affective, psychotic, and personality disorders. Studies were identified using PubMed and PsycINFO. Studies met the following criteria for inclusion in the analysis: availability in peer-reviewed English journals, use of human subjects, prenatal exposure to famine, and psychopathology in adulthood defined by diagnostic criteria as an outcome. Fixed effect relative risks (RRs) were calculated for affective, psychotic, and personality domains. Furthermore, timing of exposure was assessed as an effect modifier in our analysis, defined by the index trimester at the height of famine. Our meta-analysis found that adults exposed in utero during the 1st trimester were at a significant increased risk of psychotic disorders (RR=1.46, 95% CI=1.08, 1.97, p=0.014), and personality disorders (RR=2.31, 95% CI=1.36, 3.92, p=0.002). Those exposed during the 2nd trimester were at a significant increased risk of affective disorders (RR=1.45, 95% CI=1.22, 1.72, p<0.0001), and psychotic disorders (RR=1.46, 95% CI=1.13, 1.89, p=0.004). Similarly, those exposed in the 3rd trimester were at a significant increased risk of affective disorders (RR=1.33, 95% CI=1.13, 1.57, p=0.0001), and psychotic disorders RR=1.47, 95% CI=1.10, 1.97, p=0.010). Our findings suggest that there is differential risk across the different domains of psychopathology by trimester of exposures. This meta-analysis underscores the need for further investigation into the mechanisms underlying prenatal maternal nutrition and offspring psychopathology where magnitude of elevated risk differs by the exposure timing during pregnancy.

Ionic mechanisms underlying repetitive high-frequency burst firing in supragranular cortical neurons.

Neocortical neurons in awake, behaving animals can generate high-frequency (>300 Hz) bursts of action potentials, either in single bursts or in a repetitive manner. Intracellular recordings of layer II/III pyramidal neurons were obtained from adult ferret visual cortical slices maintained in vitro to investigate the ionic mechanisms by which a subgroup of these cells generates repetitive, high-frequency burst discharges, a pattern referred to as "chattering." The generation of each but the first action potential in a burst was dependent on the critical interplay between the afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs) that followed each action potential. The spike-afterdepolarization and the generation of action potential bursts were dependent on Na(+), but not Ca(2+), currents. Neither blocking of the transmembrane flow of Ca(2+) nor the intracellular chelation of free Ca(2+) with BAPTA inhibited the generation of intrinsic bursts. In contrast, decreasing the extracellular Na(+) concentration or pharmacologically blocking Na(+) currents with tetrodotoxin, QX-314, or phenytoin inhibited bursting before inhibiting action potential generation. Additionally, a subset of layer II/III pyramidal neurons could be induced to switch from repetitive single spiking to a burst-firing mode by constant depolarizing current injection, by raising extracellular K(+) concentrations, or by potentiation of the persistent Na(+) current with the Na(+) channel toxin ATX II. These results indicate that cortical neurons may dynamically regulate their pattern of action potential generation through control of Na(+) and K(+) currents. The generation of high-frequency burst discharges may strongly influence the response of postsynaptic neurons and the operation of local cortical networks.

Firing pattern modulation by oscillatory input in supragranular pyramidal neurons.

Neocortical neurons in vivo receive periodic stimuli due to feedforward input from the periphery as well as local cellular and circuit properties. In order to understand how neurons process such information, the responses of neurons to periodic sine wave current stimuli of varying frequencies and amplitudes were investigated. Sine wave stimuli were injected into pyramidal cells of young adult ferret visual cortical slices in vitro using sharp microelectrodes. To simulate higher resting membrane potentials observed in vivo a slight depolarizing current was injected to bring the neuron just to threshold. Initially, neurons discharged at least one action potential per sine wave cycle, but as the frequency was increased, a point was reached where this one-to-one responsiveness was lost. This critical frequency was dependent upon the injected sine wave amplitude and the magnitude of the underlying steady-state depolarization, and was correlated with spike width. Larger steady-state depolarizations and thinner action potentials corresponded to higher critical frequencies. Thus, when a neuron was very active it could respond in a one-to-one fashion over a greater range of frequencies than with the smallest DC offset. The results suggest that the frequency-following characteristics of individual cortical neurons can be modulated by the activity state of the neuron itself.

Effects of baclofen and phaclofen on receptive field properties of rat whisker barrel neurons.

Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. Iontophoretically-applied (-)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABAA and GABAB mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution.

Auditory-motor interactions in pediatric motor speech disorders: neurocomputational modeling of disordered development.

BACKGROUND/PURPOSE: Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. METHOD: In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. RESULTS: Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. CONCLUSIONS: These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. LEARNING OUTCOMES: The reader will be able to: (1) identify the difficulties in studying disordered speech motor development; (2) describe the differences in speech motor characteristics between SSD and subtype CAS; (3) describe the different types of learning that occur in the sensory-motor system during babbling and early speech acquisition; (4) identify the neural control subsystems involved in speech production; (5) describe the potential role of auditory self-monitoring in developmental speech disorders.

Physiology and morphology of inverted pyramidal neurons in the rodent neocortex.

An increasing number of studies indicate that there exists greater diversity of cortical neurons than previously appreciated. In the present report, we use a combination of physiological and morphological methods to characterize cortical neurons in infragranular layers with apical dendrites pointing toward the white-matter compared to those neurons with apical dendrites pointing toward the pia in both mouse and rat neocortex. Several features of the dendritic morphology and intrinsic and synaptic physiology of these "inverted" neurons revealed numerous differences among this cell type between species. We also found differences between the different cell types within the same species. These data reveal that similar cell types in the rat and mouse may not always share similar physiological and morphological properties. These data are relevant to models of information processing through micro- and larger neocortical circuits and indicate that different cell types found within similar lamina can have different functional properties.

Whisking in air: encoding of kinematics by trigeminal ganglion neurons in awake rats.

Active sensing requires the brain to distinguish signals produced by external inputs from those generated by the animal's own movements. Because the rodent whisker musculature lacks proprioceptors, we asked whether trigeminal ganglion neurons encode the kinematics of the rat's own whisker movements in air. By examining the role of kinematics, we have extended previous findings showing that many neurons that respond during such movements do not do so consistently. Nevertheless, the majority ( approximately 70%) of trigeminal ganglion neurons display significant correlations between firing rate and a kinematic parameter, and a subset, approximately 30%, represent kinematics with high reliability. Preferential firing to movement direction was observed but was strongly modulated by movement amplitude and speed. However, in contrast to the precise time-locking that occurs in response to active whisker contacts, whisker movements in air generate temporally dispersed responses that are not time-locked to the onset of either protractions or retractions.

Physiology and morphology of callosal projection neurons in mouse.

In the mammalian neocortex, the corpus callosum serves as the major source of interhemispheric communication, composed of axons from callosal neurons located in supragranular (II/III) and infragranular (V/VI) layers. We sought to characterize the physiology and morphology of supragranular and infragranular callosal neurons in mice using retrograde tracers and whole-cell patch clamp recordings. Whole-cell patch clamp recordings were made from retrogradely labeled callosal neurons following unilateral injection of fluorescent latex microspheres in the contralateral sensory-motor cortex. Following recordings and biocytin dialysis, labeled neurons were reconstructed using computer-assisted camera lucida (Neurolucida) for morphological analyses. Whole-cell recordings revealed that callosal neurons in both supra- and infragranular layers display very similar intrinsic membrane properties and are characteristic regular-spiking neurons. Morphological features examined from biocytin-filled reconstructions as well as retrogradely BDA labeled cells did not reveal any differences. Analysis of spontaneous postsynaptic potentials from callosal neurons did reveal several differences including average amplitude, frequency, and decay time. These findings suggest that callosal neurons in both supra- and infragranular layers have similar phenotypes though belong to different local, intracortical networks.

Slow adaptation in fast-spiking neurons of visual cortex.

Fast-spiking (FS) neurons are a class of inhibitory interneurons classically characterized as having short-duration action potentials (<0.5 ms at half height) and displaying little to no spike-frequency adaptation during short (<500 ms) depolarizing current pulses. As a consequence, the resulting injected current intensity versus firing frequency relationship is typically steep, and they can achieve firing frequencies of < or =1 kHz. Here we have investigated the properties of FS neurons discharges on a longer time scale. Twenty second discharges were induced in electrophysiologically identified FS neurons by means of current injection either with sinusoidal current or with square pulses. We found that virtually all FS neurons recorded in cortical slices do show spike-frequency adaptation but with a slow time course (tau = 2-19 s). This slow time course has precluded the observation of this property in previous studies that used shorter pulses. Contrary to the classical view of FS neurons functional properties, long-duration discharges were followed by a slow afterhyperpolarization lasting < or =23 s. During this postadaptation period, the excitability of the neurons was decreased on average for 16.7 +/- 6.8 s, therefore rendering the cell less responsive to subsequent afferent inputs. Slow adaptation is also reported here for FS neurons recorded in vivo. This longer time scale of adaptation in FS neurons may be critical for balancing excitation and inhibition as well as for the understanding of cortical network computations.

Chlorotic girls, 1870-1920: a historical perspective on female adolescence.

In light of the current interest in anorexia nervosa, this historical study explores the relationship of culture to age- and gender-specific symptomatologies. Between 1870 and 1920, chlorosis, a form of anemia, was widely reported in female adolescents in the United States. Diagnosis occurred on both the clinical and popular levels, yet neither the etiology nor the symptoms were precisely clear. Treatment generally included rest and large doses of iron salts. In large part, chlorosis was a cultural construction embedded in the context of Victorian medicine and family life. Physicians expected to see chlorosis in adolescent girls in the process of sexual maturation; girls learned to have the disease from family, friends, the popular press, and their doctors. Changes in diet and nutrition after 1900, coupled with increased understanding of ovarian function and iron deficiency anemia, provide only a partial explanation of the disease's eventual decline. By 1920, a changed social environment made chlorosis a social liability for girls and their mothers.

Cortical columnar processing in the rat whisker-to-barrel system.

Controlled whisker stimulation and single-unit recordings were used to elucidate response transformations that occur during the processing of tactile information from ventral posterior medial thalamus (VPM) through cortical columns in the rat whisker/barrel cortex. Whiskers were either deflected alone, using punctate ramp-and-hold stimuli, or in combination with a random noise vibration applied simultaneously to two or more neighboring whiskers. Quantitative data were obtained from five anatomically defined groups of neurons based on their being located in: VPM, layer IV barrels, layer IV septa, supragranular laminae, and infragranular laminae. Neurons in each of these populations displayed characteristic properties related to their response latency and time course, relative magnitudes of responses evoked by stimulus onset versus offset, strength of excitatory responses evoked by the noise stimulus, and/or the degree to which the noise stimulus, when applied to neighboring whiskers, suppressed or facilitated responses evoked by the columnar whisker. Results indicate that within layer IV itself there are at least two anatomically distinct networks, barrel and septum, that independently process afferent information, transforming thalamic input in similar but quantitatively distinguishable ways. Transformed signals are passed on to circuits in supragranular and infragranular laminae. In the case of supragranular neurons, evidence suggests that circuits there function in a qualitatively different fashion from those in layer IV, diminishing response differentials between weak and strong inputs, rather than enhancing them. Compared to layer IV, the greater heterogeneity of receptive field properties in nongranular layers suggests the existence of multiple, operationally distinct local circuits in the output layers of the cortical column.

Spatial gradients and inhibitory summation in the rat whisker barrel system.

1. Extracellular single-unit recordings and controlled whisker stimuli were used to compare response properties of cells in the barreloids of the ventral posterior medial nucleus of the thalamus and the barrels in the rat primary somatosensory cortex. Whiskers were deflected alone or in combinations involving up to four immediately adjacent whiskers to assess their relative inhibitory and excitatory contributions to individual receptive fields. Quantitative data were obtained from 51 thalamocortical units (TCUs), 79 "regular-spiking" barrel neurons (RSUs), and 5 "fast-spiking" barrel neurons (FSUs) in 28 normal female adult rats. 2. A random-noise generator was used to produce small, continuously varying whisker movements that were applied to one to four adjacent whiskers while the principal (columnar) whisker was displaced with the use of a ramp-and-hold deflection. RSUs displayed adjacent whisker-evoked inhibition that increased as the number of adjacent whiskers stimulated was incremented. Asymptotic levels of inhibition were reached with the application of the noise stimulus to two or three adjacent whiskers depending on which particular combinations were deflected. By contrast, TCUs and FSUs showed weak, or no, surround inhibition. 3. As the number of adjacent whiskers stimulated increased, the background (prestimulus) activity in TCUs and FSUs increased, whereas displayed background activity in RSUs was relatively unaffected. The increase in background activity observed in the FSUs is hypothesized to mediate adjacent whisker-evoked inhibition in the RSUs. 4. A spatial gradient of adjacent whisker inhibition was observed in RSUs. The caudally adjacent whisker evoked more inhibition than the rostrally adjacent whisker, and the ventral more than the dorsal. A cortical origin for the gradient is suggested by the finding that TCUs did not show a spatial inhibitory gradient. 5. As the noise stimulus was applied to an increasing number of adjacent whiskers, RSUs became more sharply tuned for deflection angles. Neither TCUs nor FSUs showed increases in angular tuning. 6. Inhibition worked disproportionately in RSUs to inhibit those responses that were initially the least robust. For example, inhibition was most effective at reducing responses to nonpreferred versus preferred whisker deflection angles. 7. To assess the principal whisker's effect on adjacent whisker excitatory responses, the noise stimulus was applied to the principal whisker. In RSUs, principal whisker-evoked inhibition was more potent than adjacent whisker-evoked inhibition. FSUs were excited to a greater extent by the application of the noise stimulus to the principal whisker than to adjacent whiskers. TCUs did not display principal whisker-evoked inhibition. 8. Inhibition within the barrel serves as a contrast enhancement mechanism to differentiate small versus large magnitude responses. Less vigorous responses, such as those associated with perturbations of noncolumnar whiskers and inputs from nonoptimal deflection angles, are more strongly suppressed. During active touch, when many whiskers simultaneously palpate an object, these inhibitory interactions could effectively increase the "principal whiskerness" of the cortical column.

Circuit dynamics and coding strategies in rodent somatosensory cortex.

Previous experimental studies of both cortical barrel and thalamic barreloid neuron responses in rodent somatosensory cortex have indicated an active role for barrel circuitry in processing thalamic signals. Previous modeling studies of the same system have suggested that a major function of the barrel circuit is to render the response magnitude of barrel neurons particularly sensitive to the temporal distribution of thalamic input. Specifically, thalamic inputs that are initially synchronous strongly engage recurrent excitatory connections in the barrel and generate a response that briefly withstands the strong damping effects of inhibitory circuitry. To test this experimentally, we recorded responses from 40 cortical barrel neurons and 63 thalamic barreloid neurons evoked by whisker deflections varying in velocity and amplitude. This stimulus evoked thalamic response profiles that varied in terms of both their magnitude and timing. The magnitude of the thalamic population response, measured as the average number of evoked spikes per stimulus, increased with both deflection velocity and amplitude. On the other hand, the degree of initial synchrony, measured from population peristimulus time histograms, was highly correlated with the velocity of whisker deflection, deflection amplitude having little or no effect on thalamic synchrony. Consistent with the predictions of the model, the cortical population response was determined largely by whisker velocity and was highly correlated with the degree of initial synchrony among thalamic neurons (R(2) = 0.91), as compared with the average number of evoked thalamic spikes (R(2) = 0.38). Individually, the response of nearly all cortical cells displayed a positive correlation with deflection velocity; this homogeneity is consistent with the dependence of the cortical response on local circuit interactions as proposed by the model. By contrast, the response of individual thalamic neurons varied widely. These findings validate the predictions of the modeling studies and, more importantly, demonstrate that the mechanism by which the cortex processes an afferent signal is inextricably linked with, and in fact determines, the saliency of neural codes embedded in the thalamic response.

A quantitative population model of whisker barrels: re-examining the Wilson-Cowan equations.

Beginning from a biologically based integrate and fire model of a rat whisker barrel, we employ semirigorous techniques to reduce the system to a simple set of equations, similar to the Wilson-Cowan equations, while retaining the ability for both qualitative and quantitative comparisons with the biological system. This is made possible through the clarification of three distinct measures of population activity: voltage, firing rate, and a new term called synaptic drive. The model is activated by prerecorded neural activity obtained from thalamic "barreloid" neurons in response to whisker stimuli. Output is produced in the form of population PSTHs, one each corresponding to activity of spiny (excitatory) and smooth (inhibitory) barrel neurons, which is quantitatively comparable to PSTHs from electrophysiologically studied regular-spike and fast-spike neurons. Through further analysis, the model yields novel physiological predictions not readily apparent from the full model or from experimental studies.

Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and simulated whisker barrels.

1. Carbon fiber multibarrel glass microelectrodes were used to record extracellular single-unit activity during microiontophoretic application of gamma-aminobutyric acid (GABA) or bicuculline methiodide (BMI) onto layer IV barrel neurons in the somatosensory cortex of fentanyl-sedated rats. Excitatory and inhibitory aspects of the neurons' receptive fields were quantified with the use of controlled whisker stimuli. The principally activating whisker and one of its immediately adjacent neighbors were deflected alone or in paired combinations involving a condition-test paradigm. 2. Units were distinguished electrophysiologically on the basis of the time course of their action potential waveforms. Data were obtained from 26 regular-spike units (RSUs; presumed spiny stellate cells) and 7 fast-spike units (FSUs; presumed GABAergic neurons). An average of 15.0 nA of GABA produced a one-third to one-half reduction in RSU responses evoked by the maximally effective stimulus. An average of 8.7 nA of BMI was needed to counteract this reduction. This amount of BMI, in the absence of exogenous GABA, was found to increase average RSU and FSU responses by 98 and 53%, respectively, relative to predrug levels. 3. For RSUs, the BMI-induced twofold increase in responses evoked by moving the principal whisker at the neuron's best deflection angle was accompanied by an almost threefold increase in responses evoked by similarly moving an adjacent whisker. Disproportionately large percentage increases were also seen for responses to nonpreferred directions of principal and adjacent whisker movement. BMI thus effectively increased receptive field size and decreased angular tuning. Similarly, responses to stimulus offsets, which are normally smaller than ON responses, were increased proportionally more. 4. Predrug responses of FSUs were more vigorous than those of RSUs. However, FSUs showed a similar inverse relationship between percentage increase with BMI and initial response magnitude, although the proportional increases were less pronounced. 5. GABA, like BMI, had the greatest proportional effects on those responses that were initially smallest. It produced results opposite those of BMI, effectively decreasing receptive field size and sharpening angular tuning. 6. A previously described computational model of a barrel was tested for its ability to reproduce quantitatively the effects of BMI and GABA. The application of BMI was simulated by decreasing the strength of the inhibitory inputs onto the particular cell under study in the model network. GABA microiontophoresis was simulated by adding a constant hyperpolarizing voltage. The model RSUs and FSUs displayed proportional changes in response magnitude that were quantitatively similar to those of their biological counterparts. 7. Surround inhibition was greatly attenuated by BMI application, both for the real and simulated barrel neurons. Disinhibition was less pronounced for the former, perhaps because, unlike the simulated neurons, they also possess GABAB receptors, which are unaffected by BMI. 8. We conclude that the inhibitory receptive field properties of barrel neurons can be explained by intrabarrel inhibition and that the expansion of receptive field size and loss of angular tuning with BMI is due to an enhanced effectiveness of convergent, multi-whisker thalamocortical input. Examination of the model neurons' behavior suggests that the altered activity in response to GABA or BMI application, respectively, can be explained by the nonlinear effects of shifting somal membrane potential away from or toward the neuron's firing threshold.

Laminar differences in bicuculline methiodide's effects on cortical neurons in the rat whisker/barrel system.

Extracellular unit recordings were made at various depths within SmI barrel cortex of immobilized, sedated rats, in the presence and absence of titrated amounts of the GABA(A) receptor antagonist bicuculline methiodide (BMI). Principal and adjacent whiskers were moved singly, or in paired combination in a condition-test paradigm, to assess excitatory and inhibitory receptive field (RF) characteristics. Neurons were classified as regular- or fast-spike units, and divided into three laminar groups: supragranular, granular (barrel), and infragranular. BMI increased response magnitude and duration, but did not affect response latencies. The excitatory RFs of barrel units, which are the most tightly focused on the principal whisker, were the most greatly defocused by BMI; infragranular units were least affected. All three layers had approximately equal amounts of adjacent whisker-evoked, surround inhibition, but BMI counteracted this inhibition substantially in barrel units and less so in infragranular units. The effects of BMI were most consistent in the barrel; more heterogeneity was found in the non-granular layers. These lamina-dependent effects of BMI are consistent with the idea that between-whisker inhibition is generated mostly within individual layer IV barrels as a result of the rapid engagement of strong, local inhibitory circuitry, and is subsequently embedded in layer IV's output to non-layer IV neurons. The latter's surround inhibition is thus relatively resistant to antagonism by locally applied BMI. The greater heterogeneity of non-granular units in terms of RF properties and the effects of BMI is consistent with other findings demonstrating that neighboring neurons in these layers may participate in different local circuits.