Dorsomedial Cortex Research Articles

Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study.

Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood. To investigate the neural correlates of subchronic antidepressant administration. We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration. Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration. To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.

Peripherally acting anti-CGRP monoclonal antibodies alter cortical gray matter thickness in migraine patients: A prospective cohort study

Migraine is underpinned by central nervous system neuroplastic alterations thought to be caused by the repetitive peripheral afferent barrage the brain receives during the headache phase (cortical hyperexcitability). Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) are highly effective migraine preventative treatments. Their ability to alter brain morphometry in treatment-responders vs. non-responders is not well understood. Our aim was to determine the effects of the anti-CGRP-mAb galcanezumab on cortical thickness after 3-month treatment of patients with high-frequency episodic or chronic migraine. High-resolution magnetic resonance imaging was performed pre- and post-treatment in 36 migraine patients. In this group, 19 patients were classified responders (≥50 % reduction in monthly migraine days) and 17 were considered non-responders (<50 % reduction in monthly migraine days). Following cross-sectional processing to analyze the baseline differences in cortical thickness, two-stage longitudinal processing and symmetrized percent change were conducted to investigate treatment-related brain changes. At baseline, no significant differences were found between the responders and non-responders. After 3-month treatment, decreased cortical thickness (compared to baseline) was observed in the responders in regions of the somatosensory cortex, anterior cingulate cortex, medial frontal cortex, superior frontal gyrus, and supramarginal gyrus. Non-responders demonstrated decreased cortical thickness in the left dorsomedial cortex and superior frontal gyrus. We interpret the cortical thinning seen in the responder group as suggesting that reduction in head pain could lead to changes in neural swelling and dendritic complexity and that such changes reflect the recovery process from maladaptive neural activity. This conclusion is further supported by our recent study showing that 3 months after treatment initiation, the incidence of premonitory symptoms and prodromes that are followed by headache decreases but not the incidence of the premonitory symptoms or prodromes themselves (that is, cortical thinning relates to reductions in the nociceptive signals in the responders). We speculate that a much longer recovery period is required to allow the brain to return to a more ‘normal’ functioning state whereby prodromes and premonitory symptoms no longer occur.

Negative Effects on Neurogenesis, Ovariogenesis, and Fitness in Sea Turtle Hatchlings Associated to ex situ Incubation Management

Sea turtle egg relocation and hatchery incubation (hereafter termed ex situ incubation) is an effective strategy to protect clutches when in situ egg incubation is not viable. Nevertheless, it negatively affects the ontogenesis of male gonads and brain areas homologous to the mammalian hippocampus, as well as body size and fitness. Thus, it is imperative to analyze the effects of ex situ incubation on other developmental aspects and extend these observations to females. This work evaluated the effect of ex situ management on neurogenesis (cell proliferation in the dorsal and medial ventricular zones, neuronal integration in the dorsomedial and medial cortices), ovary cell proliferation, body size (mass and length) and self-righting ability. Additionally, this study examined if the incubation microenvironment is different between in situ and ex situ nests and whether it could contribute to explain the biological traits. An analysis of principal components showed differences in biological variables of hatchlings between in situ and ex situ clutches, driven by contrasting temperatures and silt composition. Each biological variable was also analyzed with linear mixed models using in situ vs. ex situ clutches, abiotic variables and their interaction. Turtles from ex situ clutches showed: (1) fewer proliferating cells in the dorsal and medial ventricular zones; (2) less mature neurons in the dorsomedial and medial cortices; (3) ovaries with a lesser number of proliferating cells; (4) lower body mass and length at emergence; and (5) slower self-righting time. Together, the results suggest that ex situ incubation in hatcheries is related to a slowing down of neurogenesis, ovariogenesis, body size and self-righting ability in hatchlings. Future studies should evaluate the effect of ex situ incubation on cognitive and reproductive performance to understand the long-term consequences of altered organogenesis. These studies should also disentangle the differential contribution of egg movement, reburial, nesting environment and parental origin to development. This information would likely result in better conservation strategies for sea turtles.

A twisted visual field map in the primate dorsomedial cortex predicted by topographic continuity.

Adjacent neurons in visual cortex have overlapping receptive fields within and across area boundaries, an arrangement theorized to minimize wiring cost. This constraint is traditionally thought to create retinotopic maps of opposing field signs (mirror and nonmirror visual field representations) in adjacent areas, a concept that has become central in current attempts to subdivide the extrastriate cortex. We simulated the formation of retinotopic maps using a model that balances constraints imposed by smoothness in the representation within an area and by congruence between areas. As in the primate cortex, this model usually leads to alternating mirror and nonmirror maps. However, we found that it can also produce a more complex type of map, consisting of sectors with opposing field sign within a single area. Using fully quantitative electrode array recordings, we then demonstrate that this type of inhomogeneous map exists in the controversial dorsomedial region of the primate extrastriate cortex.

Flexible use of allocentric and egocentric spatial memories activates differential neural networks in mice

Goal-directed navigation can be based on world-centered (allocentric) or body-centered (egocentric) representations of the environment, mediated by a wide network of interconnected brain regions, including hippocampus, striatum and prefrontal cortex. The relative contribution of these regions to navigation from novel or familiar routes, that demand a different degree of flexibility in the use of the stored spatial representations, has not been completely explored. To address this issue, we trained mice to find a reward relying on allocentric or egocentric information, in a modified version of the cross-maze task. Then we used Zif268 expression to map brain activation when well-trained mice were required to find the goal from a novel or familiar location. Successful navigation was correlated with the activation of CA1, posterior-dorsomedial striatum, nucleus accumbens core and infralimbic cortex when allocentric-trained mice needed to use a novel route. Allocentric navigation from a familiar route activated dorsomedial striatum, nucleus accumbens, prelimbic and infralimbic cortex. None of the structures analyzed was significantly activated in egocentric-trained mice, irrespective of the starting position. These data suggest that a flexible use of stored allocentric information, that allows goal finding even from a location never explored during training, induces a shift from fronto-striatal to hippocampal circuits.

The fornix acts as a permissive corridor for septal neuron migration beyond the diencephalic-telencephalic boundary

Neuronal migration is essential for constructing functional neural networks. Two posterior septal (PS) nuclei, the triangular septal nucleus and bed nuclei of the anterior commissure, are involved in fear and anxiety. During development, glutamatergic PS neurons undergo long-distance rostrodorsal migration from the thalamic eminence (TE) of the diencephalon, then settle in the caudalmost telencephalon. However, the developmental behavior of PS neurons and the guidance structures facilitating their migration remain unknown. We previously demonstrated the migration of PS neurons along the fornix, a major efferent pathway from the hippocampal formation. Here, we show that the postcommissural fornix is essential for PS neuron migration which is largely confined to its axonal tract, which grows in the opposite direction as PS neuron migration. Fornical axons reach the TE prior to initiation of PS neuron rostrodorsal migration. Ectopic expression of Semaphorin 3 A in the dorsomedial cortex resulted in defective fornix formation. Furthermore, loss of the postcommissural fornix stalled PS neuron migration resulting in abnormal accumulation near their origin. This suggests that PS neurons utilize the postcommissural fornix as a permissive corridor during migration beyond the diencephalic-telencephalic boundary. This axonal support is essential for the functional organization of the heterogeneous septal nuclear complex.

Evidence for Reactive Neurogenesis in the Forebrain of the Leopard Gecko (Eublepharis macularius)

Neurogenesis is the ability to generate new neurons from resident progenitor populations. Although best understood as a normal physiological process, in several species of teleost fish and salamanders neurogenesis is also capable of replacing neurons lost or damaged due to injury – so called reactive neurogenesis. While reactive neurogenesis does not appear to resolve brain injuries in mammals, for reptiles less is known. Here, we investigated reactive neurogenesis in the lizard Eublepharis macularius, the leopard gecko. To initiate reactive neurogenesis, we administered geckos with a single dose of the neurotoxin 3‐acetylpyridine (3AP). Using the cell death markers Fluoro‐Jade and the TUNEL assay, we determined that neuronal loss occurs within 4 days following 3AP administration. Cell death is largely restricted to the medial and dorsomedial cortices, areas of the forebrain widely accepted to be the reptilian homologs of the mammalian hippocampus and neocortex, respectively. As evidenced by a decrease in the number of cells expressing the mature neuronal marker NeuN, cell death within these regions appears to selectively target neurons. Remarkably, by 30 days following 3AP administration the medial and dorsomedial cortices appear to be structurally restored with a pattern of NeuN expression that closely resembles the uninjured brain. These data provide the first evidence that the leopard gecko is capable of reactive neurogenesis, a phenomenon otherwise rare among amniotes (reptiles and mammals).Support or Funding InformationNatural Sciences and Engineering Research Council (NSERC), Discovery Grant 400358)

Loss of Dmrt5 Affects the Formation of the Subplate and Early Corticogenesis.

Dmrt5 (Dmrta2) and Dmrt3 are key regulators of cortical patterning and progenitor proliferation and differentiation. In this study, we show an altered apical to intermediate progenitor transition, with a delay in SP neurogenesis and premature birth of Ctip2+ cortical neurons in Dmrt5−/− mice. In addition to the cortical progenitors, DMRT5 protein appears present in postmitotic subplate (SP) and marginal zone neurons together with some migrating cortical neurons. We observed the altered split of preplate and the reduced SP and disturbed radial migration of cortical neurons into cortical plate in Dmrt5−/− brains and demonstrated an increase in the proportion of multipolar cells in primary neuronal cultures from Dmrt5−/− embryonic brains. Dmrt5 affects cortical development with specific time sensitivity that we described in two conditional mice with slightly different deletion time. We only observed a transient SP phenotype at E15.5, but not by E18.5 after early (Dmrt5lox/lox;Emx1Cre), but not late (Dmrt5lox/lox;NestinCre) deletion of Dmrt5. SP was less disturbed in Dmrt5lox/lox;Emx1Cre and Dmrt3−/− brains than in Dmrt5−/− and affects dorsomedial cortex more than lateral and caudal cortex. Our study demonstrates a novel function of Dmrt5 in the regulation of early SP formation and radial cortical neuron migration.Summary StatementOur study demonstrates a novel function of Dmrt5 in regulating marginal zone and subplate formation and migration of cortical neurons to cortical plate.

Patterns of c-Fos expression in telencephalic areas of Tropidurus hygomi (Iguania: Tropiduridae) exposed to different social contexts

Social behavior in lizards contributes to understanding biological standards and provides models for structuring research about neural mechanisms. Studies have confirmed the effectiveness of comparative models and evidence has contributed to clarifying adult brain plasticity phenomenon when exposed to different stimuli. The expression of c-Fos has been widely used to identify brain areas involved in different behavioral stimuli. The purpose of the present study was to map the expression of c-Fos protein in different telencephalic areas of the lizard Tropidurus hygomi after they were exposed to visual stimuli with another individual of the same species in different social contexts. Lizards were allocated to one of four groups: 1) control group (CTL) – males not exposed to any other animal; 2) exposure to juvenile (EJU) – males exposed to a juvenile; 3) exposure to male (EMA) – males exposed to another adult male; and 4) exposure to females (EFE) –males exposed to female. The EFE group exhibited a greater number of c-Fos + cells in cortical areas (medial cortex – MC and dorsomedial cortex – DMC) and in amygdala (AMY), showing a possible relationship between these structures and behavioral components. Studies like this can contribute significantly to a better understanding of neurophysiological, behavioral, and evolutive aspects.

Regional changes in ∆FosB expression in rat brain following MDMA self-administration predict increased sensitivity to effects of locally infused MDMA.

Repeated exposure to drugs produces a plethora of persistent brain changes, some of which underlie the development of drug addiction. An important objective of addiction research is to identify the brain changes that might mediate the transition from drug use to drug misuse. The persistent accumulation of the transcription factor, ∆FosB, following repeated drug exposure provides a means of achieving this objective. Experiments were conducted on sexually mature male Sprague-Dawley rats. The effects of extensive 3,4-methylenedioxymethamphetamine (MDMA) self-administration on immunohistochemical measurements of ∆FosB accumulation in 12 brain regions was compared with a matched, drug-naive, control group. Other groups were pretreated with MDMA (0.0 or 10.0 mg/kg, ip, once daily for 5 days), and the locomotor-activating effect of MDMA (200 μg/side) microinjected bilaterally into brain regions selected on the basis of the ∆FosB results was subsequently determined. MDMA self-administration significantly increased ∆FosB expression in the nucleus accumbens core, ventromedial and dorsomedial caudate-putamen, anterior cingulate, prelimbic, infralimbic, and orbitofrontal cortex, and both the central and basolateral amygdala, but not in the ventrolateral or dorsolateral caudate-putamen. Increases in the nucleus accumbens shell were substantial but were not significant following statistical correction for multiple comparisons. MDMA pretreatment enhanced MDMA-produced hyperactivity only when administered into the nucleus accumbens or the medial, but not the lateral, caudate-putamen, mirroring the ∆FosB results. These data compare favorably to results following repeated exposure to other drugs of abuse and support the idea of common neuroplastic changes following repeated drug exposure.

The human body odor compound androstadienone increases neural conflict coupled to higher behavioral costs during an emotional Stroop task

The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing.For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI.Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related brain activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy.To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words.

Expression of regulatory genes in the embryonic brain of a lizard and implications for understanding pallial organization and evolution.

The comparison of gene expression patterns in the embryonic brain of mouse and chicken is being essential for understanding pallial organization. However, the scarcity of gene expression data in reptiles, crucial for understanding evolution, makes it difficult to identify homologues of pallial divisions in different amniotes. We cloned and analyzed the expression of the genes Emx1, Lhx2, Lhx9, and Tbr1 in the embryonic telencephalon of the lacertid lizard Psammodromus algirus. The comparative expression patterns of these genes, critical for pallial development, are better understood when using a recently proposed six‐part model of pallial divisions. The lizard medial pallium, expressing all genes, includes the medial and dorsomedial cortices, and the majority of the dorsal cortex, except the region of the lateral cortical superposition. The latter is rich in Lhx9 expression, being excluded as a candidate of dorsal or lateral pallia, and may belong to a distinct dorsolateral pallium, which extends from rostral to caudal levels. Thus, the neocortex homolog cannot be found in the classical reptilian dorsal cortex, but perhaps in a small Emx1‐expressing/Lhx9‐negative area at the front of the telencephalon, resembling the avian hyperpallium. The ventral pallium, expressing Lhx9, but not Emx1, gives rise to the dorsal ventricular ridge and appears comparable to the avian nidopallium. We also identified a distinct ventrocaudal pallial sector comparable to the avian arcopallium and to part of the mammalian pallial amygdala. These data open new venues for understanding the organization and evolution of the pallium.

Characterization of NADPH Diaphorase- and Doublecortin-Positive Neurons in the Lizard Hippocampal Formation

The lizard cortex has remarkable similarities with the mammalian hippocampus. Both regions process memories, have similar cytoarchitectural properties, and are important neurogenic foci in adults. Lizards show striking levels of widespread neurogenesis in adulthood and can regenerate entire cortical areas after injury. Nitric oxide (NO) is an important regulatory factor of mammalian neurogenesis and hippocampal function. However, little is known about its role in nonmammalian neurogenesis. Here, we analyzed the distribution, morphology, and dendritic complexity (Neurolucida reconstructions) of NO-producing neurons through NADPH diaphorase (NADPHd) activity, and how they compare with the distribution of doublecortin-positive (DCX+) neurons in the hippocampal formation of the neotropical lizard Tropidurus hispidus. NADPHd-positive (NADPHd+) neurons in the dorsomedial cortex (DMC; putatively homologous to mammalian CA3) were more numerous and complex than the ones in the medial cortex (MC; putatively homologous to the dentate gyrus). We found that NADPHd+ DMC neurons send long projections into the MC. Interestingly, in the MC, NADPHd+ neurons existed in 2 patterns: small somata with low intensity of staining in the outer layer and large somata with high intensity of staining in the deep layer, a pattern similar to the mammalian cortex. Additionally, NADPHd+ neurons were absent in the granular cell layer of the MC. In contrast, DCX+ neurons were scarce in the DMC but highly numerous in the MC, particularly in the granular cell layer. We hypothesize that NO-producing neurons in the DMC provide important input to proliferating/migrating neurons in the highly neurogenic MC.

Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/-) sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate.

Differences Between Dendritic Spines of Neurons of Different Regions of the Cerebral Cortex of the Garden Lizard, C. versicolor (Daudin)

The present study, based on neurohistological techniques (Golgi impregnation), focuses on the morphological and numerical changes in the dendritic spines of neuronal classes of the cerebral cortex in Calotes versicolor. The cerebral cortex in reptiles occupies the roof of the cerebral hemisphere and is divided into four regions viz. medial, dorsomedial, dorsal and lateral cortex. Using different characteristics such as criteria of location, dendritic tree pattern, dendritic spine covering and soma shape different neuronal types have been distinguished in the cell layer-II of medial, dorsomedial, dorsal and lateral cortex. The dendritic diameter, spine length and diameter of spine head show almost uniform pattern in all cortical regions except being slightly higher in case of the neurons of dorsomedial cortex. The multipolar and pyramidal neurons show higher dendritic diameter, spine length, spine head diameter and dendritic spine density in comparison to other neurons. The density of these neurons acts as the indicator of high or low activity of a particular region.

Abstract 3709: Acute Stroke opens Neuronal Pannexin1 Channels

Introduction: Oxygen-glucose deprivation induces neuronal uptake of the sulforhodamine-based dye SR101 via pannexin1 channels in cultured neurons and brain slices. We assessed the hypothesis that pannexin1 channels are opened during acute stroke. Methods: Focal cerebral ischemia was induced in male C57BL/6 mice (20 to 25g, n=5) by middle cerebral artery occlusion (MCAO) for 30 minutes using the intraluminal suture occlusion method. Brain slices (2mm thickness) were taken immediately after stroke and incubated at room temperature in oxygenated sucrose-modified artificial cerebral spinal fluid for 60 minutes in 3 μ M Texas Red hydrazide (TRH), a structurally similar SR101 analog selectively taken up by astrocytes under non-ischemic conditions. Five brain slices co-incubated with 1 mM probenecid (a specific pannexin1 channel blocker) and seven brain slices without were assessed for pannexin1 channel-mediated dye uptake. Following cryosectioning and NeuN immunofluorescent labelling, the proportion of neurons showing TRH uptake (mean percentage ± S.E.M.) was determined in both hemispheres by fluorescence microscopy from 114 regions within the dorsomedial and lateral cortex, and 54 regions within the striatum. In a separate mouse, 2-photon laser scanning microscopy was used to assess in vivo neuronal uptake of sulforhodamine B (an SR101 analog) during acute stroke. Detailed neuronal morphology following 30 minutes of MCAO was assessed in a separate group of transgenic mice (n=3, C57 background) expressing yellow fluorescent protein in a subpopulation of neocortical pyramidal neurons. Results: Neuron morphology was unaltered after 30 minutes MCAO in the ipsilateral and contralateral hemisphere. TRH uptake was dramatically increased in the ischemic hemisphere in the lateral neocortex (ipsilateral vs contralateral 28% ± 1.8% vs 14% ± 1.6%, p &lt; 0.0001) and striatum (ipsilateral vs contralateral 55% ± 3.0% vs 38% ± 3.1%, p = 0.005). The pannexin1-specific blocker probenecid reduced ipsilateral dye uptake to the same level seen contralaterally: (ipsilateral vs contralateral) lateral cortex 14% ± 2.5% vs 16% ± 2.6% (p = 0.58), dorsomedial cortex 13% ± 2.0% vs 16% ± 2.1% (p=0.31), and striatum 40% ± 3.2% vs 36% ± 2.2% (p=0.31). In vivo uptake of sulforhodamine B was demonstrated in neocortical and striatal neurons only in the ipsilateral hemisphere by 2-photon laser scanning microscopy. Conclusion: The opening of neuronal pannexin1 channels is widespread specifically in ischemic tissue within 30 minutes of MCAO onset. Pannexin1 channel opening appears to precede and possibly contribute to early neuronal membrane breakdown during acute stroke.

AS07-02 - Brain imaging: help for the understanding of suicidal vulnerability

Suicidal behaviour may be best understood within a stress-vulnerability model. The vulnerability is a key element that differentiates psychiatric patients who are at high risk versus those at lower risk of suicide. Neurobiological studies have strongly influenced the concept of a vulnerability to suicidal behaviour. Moreover neuropsychological studies have reported dysfunctional cognitive processes in suicide attempters. Brain imaging is a helpful tool to better understand in vivo their neuroanatomical basis. Neuroimaging studies mainly showed the involvement of ventrolateral orbital, dorsomedial and dorsolateralprefrontal cortices and the anterior cingulate gyrus. In addition, alterations in white matter connections have been suggested. We will propose a neurocognitive model of suicidal act and will discuss the strengths and limitations of the neuroimaging approach of the pathophysiology and prediction of such complex human behaviours.

Neural Substrates of Attentive Listening Assessed with a Novel Auditory Stroop Task

A common explanation for the interference effect in the classic visual Stroop test is that reading a word (the more automatic semantic response) must be suppressed in favor of naming the text color (the slower sensory response). Neuroimaging studies also consistently report anterior cingulate/medial frontal, lateral prefrontal, and anterior insular structures as key components of a network for Stroop-conflict processing. It remains unclear, however, whether automatic processing of semantic information can explain the interference effect in other variants of the Stroop test. It also is not known if these frontal regions serve a specific role in visual Stroop conflict, or instead play a more universal role as components of a more generalized, supramodal executive-control network for conflict processing. To address these questions, we developed a novel auditory Stroop test in which the relative dominance of semantic and sensory feature processing is reversed. Listeners were asked to focus either on voice gender (a more automatic sensory discrimination task) or on the gender meaning of the word (a less automatic semantic task) while ignoring the conflicting stimulus feature. An auditory Stroop effect was observed when voice features replaced semantic content as the “to-be-ignored” component of the incongruent stimulus. Also, in sharp contrast to previous Stroop studies, neural responses to incongruent stimuli studied with functional magnetic resonance imaging revealed greater recruitment of conflict loci when selective attention was focused on gender meaning (semantic task) over voice gender (sensory task). Furthermore, in contrast to earlier Stroop studies that implicated dorsomedial cortex in visual conflict processing, interference-related activation in both of our auditory tasks was localized ventrally in medial frontal areas, suggesting a dorsal-to-ventral separation of function in medial frontal cortex that is sensitive to stimulus context.

New Calretinin-Positive Cells with Polymorphous Spines in the Mouse Forebrain during Early Postnatal Ontogeny

Immunohistochemical studies of calretinin (CR) in forebrain structures adjacent to the anterior horn of the lateral ventricle in adult mice allowed us to detect a population of previously unknown mono- and bipolar cells whose bodies and processes were coated with polymorphous spines (PS) (Morfologiya, 135, No. 3, 7-19 (2009)). CR-positive spiny (CR(+)PS) cells did not contain GAD67 and were located in the white matter and layers V-VI of the frontal area of the dorsomedial cortex close to the cingulum, the rostrodorsal part of the caudate-putamen, the anterior olfactory nucleus, and the subependyma of the dorsolateral angle of the lateral ventricle. We report here studies of the distribution of these cells in seven-day-old mice. Comparative topographic analysis of definitive and early CR(+)PS cells showed that in seven-day-old mice, CR(+)PS cells were absent from the sites at which they were seen in adults, i.e., the anterior olfactory cortex, the cortical plate, and the inner part of the neostriatum. In addition, small numbers of CR(+)PS-like cells were seen at this age within the dorsal migration pathway, at the anterior margin of the neostriatum, along the dorsal border of the neostriatum with the corpus callosum, in the subependymal layer of the lateral wall of the lateral ventricle, and in the cingulum area. These data demonstrate that CR(+)PS cells may have a postnatal origin. Experiments to verify this hypothesis were performed using postnatal administration of bromodeoxyuridine (BrdU) to mice aged 2-4 days, followed by assessment of brain sections fixed at age 20 days. Double immunolabeling of sections for CR and BrdU demonstrated the presence of CR(+)PS cells containing postnatally supplied BrdU. These data provide evidence that at least some CR(+)PS cells undergo mitosis at postnatal age. In all probability, during the period from 7 to 20 days of postnatal development, CR(+)PS cells migrate to the sites that they occupy in adult animals.

A New Population of Calretinin-Positive Cells, Presumptively Neurons, with Polymorphous Spines in the Mouse Forebrain

An immunohistochemical reaction was used to study the locations of calretinin-positive cells on frontal sections of the anterior part of the mouse cerebral cortex. A previously undescribed population of cells with a characteristic structure was found at the anterior horns of the lateral ventricles. These cells had small (8-10 microm) round bodies giving rise to one and occasionally two nodose processes bearing rare polymorphous spines (PS) and thickenings of irregular shape. The relatively thick primary processes branched into finer processes, which also formed thickenings and spines of different calibers and structures. Calretinin-positive cells with polymorphous spines (CR+PS) were located in the white subcortical matter, in layer VI, and, significantly more rarely, in layer V of the frontal area of the dorsomedial cortex close to the cingulum. In addition, CR+PS cells were present in the rostrodorsal part of the caudate nucleus-putamen complex, in the anterior olfactory nucleus, in the subependymal layer of the dorsolateral angle of the lateral ventricle and, more rarely, in its dorsal wall. In contrast to the situation in mice, CR+PS cells were not present in the brains of other animals (rats, rabbits, cats). CR+PS cells showed no colocalization of calretinin with GABA or other neuronal or glial markers. It is suggested that these cells represent a previously unknown, probably neuronal, type of cell in the mouse forebrain.