Sex differences in the ontogeny of CRF receptors during adolescent development in the dorsal raphe nucleus and ventral tegmental area

Interactions between corticotropin‐releasing factor (CRF) and monoaminergic systems originating from the dorsal raphe nucleus (DR) and ventral tegmental area (VTA) have been implicated in the etiology and pathophysiology of several stress‐related neuropsychiatric disorders such as depression and substance abuse. Sub‐regions within the DR and VTA give rise to specific projections that have unique roles in limbic‐ and reward‐related behaviors. Given that these disorders typically emerge during adolescence, it is surprising that few studies have examined the age‐, sex‐, and region‐dependent expression of CRF receptors throughout multiple stages of adolescence in these stress‐relevant circuits. To determine the ontogeny of CRF receptors during adolescent development, three regions of the DR (dorsal, caudal, and ventrolateral parts) and the posterior VTA were microdissected from Sprague‐Dawley male and female rats on postnatal day (P) 25, P35, P42, P56, and P90. Tissue was processed and analyzed with qRT‐PCR to measure CRF₁ and CRF₂ receptors. The serotonin and catecholamine enzymes in the DR and VTA, tryptophan hydroxylase 2 (TPH2) and tyrosine hydroxylase, respectively, were also analyzed for maturational differences. This study identified that CRF₁ receptors are lower in males than females within the dorsal, ventrolateral region of the DR (DRVL), which is involved in anxiety‐, stress‐, and panic‐related responses. Females had higher CRF₂ receptors compared to males in the DRVL only. Levels of TPH2 mRNA in the DRVL were overproduced transiently in females before declining into adulthood. These fundamental studies suggest that sex differences in CRF receptors should be considered when examining stress‐related neuropsychiatric disorders and their treatment. Synapse 70:125–132, 2016. © 2016 Wiley Periodicals, Inc.     

Increased functional connectivity in the ventral and dorsal streams during retrieval of novel words in professional musicians

Current models of speech and language processing postulate the involvement of two parallel processing streams (the dual stream model): a ventral stream involved in mapping sensory and phonological representations onto lexical and conceptual representations and a dorsal stream contributing to sound‐to‐motor mapping, articulation, and to how verbal information is encoded and manipulated in memory. Based on previous evidence showing that music training has an influence on language processing, cognitive functions, and word learning, we examined EEG‐based intracranial functional connectivity in the ventral and dorsal streams while musicians and nonmusicians learned the meaning of novel words through picture–word associations. In accordance with the dual stream model, word learning was generally associated with increased beta functional connectivity in the ventral stream compared to the dorsal stream. In addition, in the linguistically most demanding “semantic task,” musicians outperformed nonmusicians, and this behavioral advantage was accompanied by increased left‐hemispheric theta connectivity in both streams. Moreover, theta coherence in the left dorsal pathway was positively correlated with the number of years of music training. These results provide evidence for a complex interplay within a network of brain regions involved in semantic processing and verbal memory functions, and suggest that intensive music training can modify its functional architecture leading to advantages in novel word learning.     

Interactions of inputs from dorsal columns and ventral tracts with visual inputs on single neurons of cat superior colliculus

In cats with upper spinal lesions disconnecting the dorsal column (DC) from the spinocervicolemniscal and ventral tract (VT) systems, single unit responses in the superior colliculus could be evoked by DC and VT stimulation. Excitatory convergence, as well as facilitatory and inhibitory interactions, were observed between DC, VT, visual and auditory inputs.     

Differential roles of the dorsal and ventral hippocampus in predator odor contextual fear conditioning

The study of fear memory is important for understanding various anxiety disorders in which patients experience persistent recollections of traumatic events. These memories often involve associations of contextual cues with aversive events; consequently, Pavlovian classical conditioning is commonly used to study contextual fear learning. The use of predator odor as a fearful stimulus in contextual fear conditioning has become increasingly important as an animal model of anxiety disorders. Innate fear responses to predator odors are well characterized and reliable; however, attempts to use these odors as unconditioned stimuli in fear conditioning paradigms have proven inconsistent. Here we characterize a contextual fear conditioning paradigm using coyote urine as the unconditioned stimulus. We found that contextual conditioning induced by exposure to coyote urine produces long‐term freezing, a stereotypic response to fear observed in mice. This paradigm is context‐specific and parallels shock‐induced contextual conditioning in that it is responsive to extinction training and manipulations of predator odor intensity. Region‐specific lesions of the dorsal and ventral hippocampus indicate that both areas are independently required for the long‐term expression of learned fear. These results in conjunction with c‐fos immunostaining data suggest that while both the dorsal and ventral hippocampus are required for forming a contextual representation, the ventral region also modulates defensive behaviors associated with predators. This study provides information about the individual contributions of the dorsal and ventral hippocampus to ethologically relevant fear learning. © 2013 Wiley Periodicals, Inc.     

Regional properties of dorsal and ventral hippocampus in suppression of intralaminar thalamic unit responses

In chloralose-anesthetized. Flaxedil-paralyzed cats, the suppression of extralemniscal thalamic units by the dorsal and ventral hippocampus was investigated. Unitary responses to test somatic stimuli, recorded in centrolateral and neighboring thalamic nuclei, were interacted with conditioning electrical stimulation in different regions around the hippocampal arch, including the parahippocampal gyrus (entorhinal and retrosplenial areas). Stimulation of dorsal (DHC) and ventral (VHC) hippocampus suppressed roughly equal proportions of responses. However, within each of DHC and VHC, effectiveness depended on the region stimulated. In DHC, Fields CA1 and CA3, subiculum (SUB), and retrosplenial area, but not field CA4 with dentate gyrus (FD), while stimulation of CA1 or subiculum was almost ineffective at currents below 1.0 mA. In VHC the regions were ranked for effectiveness as follows: entorhinal cortex = CA3 > FD >SUB >CAI. No topographic relationship was found between hippocampal region and thalamic loci for unit suppression. Lemniscal-type unit responses in ventrobasal thalamus were unaffected by stimulation of the hippocampus or parahippocampal gyrus. Interruption of the fornix-fimbria system prevented suppression elicited from CA1 of DHC or from CA3 of VHC, but not from FD of VHC. It had no effect on suppression elicited from retrosplenial or entorhinal cortex. Hippocampal regional variation of effectiveness in suppressing extralemniscal pathways may contribute to the differential behavioral involvements reported for different hippocampal structures.     

Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression

Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit alterations in several parts of the serotonergic neurotransmitter system, which are in turn involved in reward processing. However, previous investigations of the serotonin transporter (SERT) focused on regional differences with varying results depending on the clinical syndrome. Here, we aimed to describe the serotonergic system of MDD patients on a network level by evaluating SERT associations across brain regions. Twenty medication free patients with major depression and 20 healthy controls underwent positron emission tomography using the radioligand [¹¹C]DASB. SERT binding potentials (BP_ND) were quantified voxel‐wise with the multilinear reference tissue model 2. In addition, SERT BP_ND was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain serotonergic neurotransmission. Whole‐brain linear regression analysis was applied to evaluate the association of DRN SERT bindings to those in projection areas, which was followed by ANCOVA to assess differences in interregional relationships between patients and controls. Although both groups showed widespread positive correlations, group differences were restricted to decreased SERT associations between the DRN and the ventral striatum (right and left respectively: t = 5.85, P < 0.05 corrected and t = 5.07, P < 0.1 corrected) when comparing MDD patients (R² = 0.11 and 0.24) to healthy subjects (R² = 0.72 and 0.66, P < 0.01 and 0.05 corrected). Adjusting for age and sex did not change these findings. This study indicates a disturbed regulation between key regions involved in reward processing via the SERT. Our interregional approach highlights the importance of evaluating pathophysiological alterations on a network level to gain complementary information in addition to regional investigations. Hum Brain Mapp 35:3857–3866, 2014. © 2014 Wiley Periodicals, Inc.     

Differential developmental refinement of the intrinsic electrophysiological properties of CA1 pyramidal neurons from the rat dorsal and ventral hippocampus

The dorsal and ventral regions of the rat longitudinal hippocampal axis are functionally distinct. That is, each region is associated with different behavioral tasks and disease susceptibilities due to underlying anatomical, and physiological differences. These differences are especially pronounced in area CA1, where significant differences in morphology, synaptic physiology, intrinsic excitability, and gene expression have been reported between CA1 pyramidal neurons from the dorsal (DHC) and ventral hippocampus (VHC). However, despite a significant amount of recent attention, a cogent picture of the intrinsic electrophysiological profile of DHC and VHC neurons has remained elusive, due, in part, to experiments performed on rats at different developmental time points. Moreover, the resulting intrinsic electrophysiological profiles are sufficiently different as to warrant a thorough investigation of the spatial and temporal changes in the intrinsic excitability of CA1 pyramidal neurons across developmental time. Accordingly, in this study, I have characterized the intrinsic electrophysiological properties of CA1 pyramidal neurons from acute hippocampal slices prepared from the DHC and VHC throughout an approximately 3‐week developmental period (P14–P37). DHC and VHC neurons exhibited distinct intra‐region changes (DHC or VHC) and inter‐region differences (DHC versus VHC) in their intrinsic electrophysiological properties, which yielded two developmental timelines: (a) a common developmental timeline describing changes observed in both DHC and VHC neurons, and (b) a differential developmental timeline highlighting unique features observed in DHC neurons. Specifically, DHC neurons exhibited significant inter‐region differences in RMP, input resistance, threshold, and spike frequency adaptation relative to VHC neurons, as well as an intra‐region change in the rebound slope (a proxy for I_h). These observations both integrate and reconcile previous work performed with rats at different developmental stages and suggest a distinct developmental trajectory for DHC neurons that might shed light on the normal physiological functions and disease susceptibility of the DHC.     

Involvement of the dorsal and ventral attention networks in visual attention span

Visual attention span (VAS), which refers to the window size of multielement parallel processing in a short time, plays an important role in higher‐level cognition (e.g., reading) as required by encoding large amounts of information input. However, it is still a matter of debate about the underlying neural mechanism of VAS. In the present study, a modified visual 1‐back task was designed by using nonverbal stimuli and nonverbal responses, in which possible influences of target presence and position were considered to identify more pure VAS processing. A task‐driven functional magnetic resonance imaging (fMRI) experiment was then performed, and 30 healthy adults participated in this study. Results of confirmatory and exploratory analyses consistently revealed that both dorsal attention network (DAN) and ventral attention network (VAN) were significantly activated during this visual simultaneous processing. In particular, more significant activation in the left superior parietal lobule (LSPL), as compared to that in the bilateral inferior frontal gyrus (IFGs), suggested a greater involvement of DAN in VAS‐related processing in contrast to VAN. In addition, it was also found that the activation in temporoparietal junctions (TPJs) were suppressed during multielement processing only in the target‐absent condition. The current results suggested the recruitment of LSPL in covert attentional shifts and top‐down control of VAS resources distribution during the rapid visual simultaneous processing, as well as the involvement of bilateral IFGs (especially RIFG) in both VAS processing and inhibitory control. The present findings might bring some enlightenments for diagnosis of the atypicality of attentional disorders and reading difficulties.     

Interactions of ventral tract and dorsal column inputs into the cat cuneate nucleus

In decerebrate- decerebellate cats with spinal lesions separating the dorsal column (DC) from the spinocervicothalamic and ventral tract (VT) pathways, conditioning VT stimulation activated a few, but inhibited most, of the cuneate neurons discharging to test DC stimulation. This VT input into the cuneate nucleus is mediated through the brain stem.     

Involvement of the dorsal and ventral attention networks in oddball stimulus processing: A meta‐analysis

The aim of this study was to provide the first, comprehensive meta‐analysis of the neuroimaging literature regarding greater neural responses to a deviant stimulus in a stream of repeated, standard stimuli, termed here oddball effects. The meta‐analysis of 75 independent studies included a comparison of auditory and visual oddball effects and task‐relevant and task‐irrelevant oddball effects. The results were interpreted with reference to the model in which a large‐scale dorsal frontoparietal network embodies a mechanism for orienting attention to the environment, whereas a large‐scale ventral frontoparietal network supports the detection of salient, environmental changes. The meta‐analysis yielded three main sets of findings. First, ventral network regions were strongly associated with oddball effects and largely common to auditory and visual modalities, indicating a supramodal “alerting” system. Most ventral network components were more strongly associated with task‐relevant than task‐irrelevant oddball effects, indicating a dynamic interplay of stimulus saliency and internal goals in stimulus‐driven engagement of the network. Second, the bilateral inferior frontal junction, an anterior core of the dorsal network, was strongly associated with oddball effects, suggesting a central role in top‐down attentional control. However, other dorsal network regions showed no or only modest association with oddball effects, likely reflecting active engagement during both oddball and standard stimulus processing. Finally, prominent oddball effects outside the two networks included the sensory cortex regions, likely reflecting attentive and preattentive modulation of early sensory activity, and subcortical regions involving the putamen, thalamus, and other areas, likely reflecting subcortical involvement in alerting responses. Hum Brain Mapp 35:2265–2284, 2014. © 2013 Wiley Periodicals, Inc .     

Gray matter volume differences between early bilinguals and monolinguals: A study of children and adults

Gray matter has been shown to be greater in early bilingual adults relative to monolingual adults in regions associated with language (Mechelli et al., 2004), and executive control (EC; Olulade et al., 2016). It is not known, however, if language experience‐dependent differences in gray matter volume (GMV) exist in children. Further, any such differences are likely not to be the same as those observed in early bilingual adults, as children have had relatively shorter duration of dual‐language exposure and/or less development of brain regions serving EC. We tested these predictions by comparing GMV in Spanish–English early bilingual and English monolingual children, and Spanish–English early bilingual and English monolingual adults (n = 122). Comparing only children revealed relatively more GMV in the bilinguals in bilateral frontal, right inferior frontal, and right superior parietal cortices (regions associated with EC). Bilinguals, however, had less GMV in left inferior parietal cortex (region associated with language). An ANOVA including these children with bilingual and monolingual adults revealed interactions of Language Background by Age Group. There were no regions of more GMV in bilinguals relative to monolinguals that were less pronounced in children than adults, despite the children''s shorter dual‐language experience. There were relative differences between bilingual and monolingual children that were more pronounced than those in adults in left precentral gyrus and right superior parietal lobule (close to, but not directly in areas associated with EC). Together, early bilingual children manifest relative differences in GMV, and, surprisingly, these do not diverge much from those observed in studies of bilingual adults.     

Hand shape selection in pantomimed grasping: interaction between the dorsal and the ventral visual streams and convergence on the ventral premotor area

In visually guided grasping, possible hand shapes are computed from the geometrical features of the object, while prior knowledge about the object and the goal of the action influence both the computation and the selection of the hand shape. We investigated the system dynamics of the human brain for the pantomiming of grasping with two aspects accentuated. One is object recognition, with the use of objects for daily use. The subjects mimed grasping movements appropriate for an object presented in a photograph either by precision or power grip. The other is the selection of grip hand shape. We manipulated the selection demands for the grip hand shape by having the subjects use the same or different grip type in the second presentation of the identical object. Effective connectivity analysis revealed that the increased selection demands enhance the interaction between the anterior intraparietal sulcus (AIP) and posterior inferior temporal gyrus (pITG), and drive the converging causal influences from the AIP, pITG, and dorsolateral prefrontal cortex to the ventral premotor area (PMv). These results suggest that the dorsal and ventral visual areas interact in the pantomiming of grasping, while the PMv integrates the neural information of different regions to select the hand posture. The present study proposes system dynamics in visually guided movement toward meaningful objects, but further research is needed to examine if the same dynamics is found also in real grasping.     

Pulvinar contributions to the dorsal and ventral streams of visual processing in primates

The visual pulvinar is part of the dorsal thalamus, and in primates it is especially well developed. Recently, our understanding of how the visual pulvinar is subdivided into nuclei has greatly improved as a number of histological procedures have revealed marked architectonic differences within the pulvinar complex. At the same time, there have been unparalleled advances in understanding of how visual cortex of primates is subdivided into areas and how these areas interconnect. In addition, considerable evidence supports the view that the hierarchy of interconnected visual areas is divided into two major processing streams, a ventral stream for object vision and a dorsal stream for visually guided actions. In this review, we present evidence that a subset of medial nuclei in the inferior pulvinar function predominantly as a subcortical component of the dorsal stream while the most lateral nucleus of the inferior pulvinar and the adjoining ventrolateral nucleus of the lateral pulvinar are more devoted to the ventral stream of cortical processing. These nuclei provide cortico-pulvinar-cortical interactions that spread information across areas within streams, as well as information relayed from the superior colliculus via inferior pulvinar nuclei to largely dorsal stream areas.     

Oscillatory dynamics in the dorsal and ventral attention networks during the reorienting of attention

The ability to reorient attention within the visual field is central to daily functioning, and numerous fMRI studies have shown that the dorsal and ventral attention networks (DAN, VAN) are critical to such processes. However, despite the instantaneous nature of attentional shifts, the dynamics of oscillatory activity serving attentional reorientation remain poorly characterized. In this study, we utilized magnetoencephalography (MEG) and a Posner task to probe the dynamics of attentional reorienting in 29 healthy adults. MEG data were transformed into the time‐frequency domain and significant oscillatory responses were imaged using a beamformer. Voxel time series were then extracted from peak voxels in the functional beamformer images. These time series were used to quantify the dynamics of attentional reorienting, and to compute dynamic functional connectivity. Our results indicated strong increases in theta and decreases in alpha and beta activity across many nodes in the DAN and VAN. Interestingly, theta responses were generally stronger during trials that required attentional reorienting relative to those that did not, while alpha and beta oscillations were more dynamic, with many regions exhibiting significantly stronger responses during non‐reorienting trials initially, and the opposite pattern during later processing. Finally, stronger functional connectivity was found following target presentation (575‐700 ms) between bilateral superior parietal lobules during attentional reorienting. In sum, these data show that visual attention is served by multiple cortical regions within the DAN and VAN, and that attentional reorienting processes are often associated with spectrally‐specific oscillations that have largely distinct spatiotemporal dynamics.     

Specific neurotrophic interactions between cortical and subcortical visual structures in developing rat: in vivo studies

The specificity of trophic interactions in the rat visual system is investigated in vivo by using a combination of tissue culture and CNS transplantation methods. In a companion paper (Repka and Cunningham: '87) we showed that explants of embryonic day 14 (E14) occipital cortex are biased to contain different cortical cell populations depending on whether the explants develop in culture with diencephalon or with optic tectum. In this study we transplanted these precultured cortical explants into the cavity created by a lesion of the occipital cortex in newborn rats and then measured the neuron-occupied volume and the numbers of thymidine-labeled cells in the surviving ipsilateral dorsal lateral geniculate nucleus (dLGN) of the host rats. The results were compared to animals with lesions but no transplants, animals with transplants of E14 cortical tissue that had not been precultured, and animals with cerebellar transplants that had been similarly precultured either with other cerebellar tissue or with diencephalon. At 5 days postlesion, both the largest dLGN volume and the greatest number of labeled dLGN neurons survive in animals with cortical transplants precultured with diencephalon or other cortex. The surviving dLGN neurons that are rescued by these transplants are generated on E15 or E16, a period that corresponds to the latter part of geniculate neurogenesis. Relatively few cells generated on E14 survive in any group of animals. Furthermore, animals with all types of cortical transplants have significantly larger volumes of surviving dLGN than animals with either lesions only or cerebellar transplants.(ABSTRACT TRUNCATED AT 250 WORDS)     

The development of glutamic acid decar☐ylase in the visual cortex and the dorsal lateral geniculate nucleus of the rat

The activity of the enzyme glutamic acid decar☐ylase was measured in the visual cortex and the dorsal lateral geniculate nucleus of the rat at several postnatal ages. The results suggest that the developmental pattern of glutamic acid decar☐ylase is reflected in the morphology of the neurons which presumably contain the enzyme.     

Changes in callosal motor fiber integrity after subcortical stroke of the pyramidal tract

In the healthy brain, there are close correlations between task-related activation of the primary motor cortex (M1), the magnitude of interhemispheric inhibition, and microstructural properties of transcallosal fiber tracts. After subcortical stroke affecting the pyramidal tract (PT), an abnormal pattern of bilateral activity develops in M1. With this prospective longitudinal study, we aimed to determine whether a morphological correlate of poststroke disinhibition could be measured within 20 days and 6 months of PT stroke. Using diffusion tensor imaging with tractography, we delineated transcallosal motor fibers (CMF) in nine PT stroke patients, six patients with subcortical infarct not affecting the PT (NonPT) and six transient ischemic attack patients. We compared changes in CMF fractional anisotropy ratios (rFA) with rFA in a distinct bundle of callosal occipital fibers (COF). At the initial time point, there were no significant differences in rFA between groups and fiber bundles. At follow-up, PT-group rFA(CMF) was significantly lower than PT-group rFA(COF) and NonPT-group rFA(CMF). PT-group rFA(CMF) decreased over time and correlated with rFA of the PT (rFA(PT)) retrograde to the infarct at 6 months. Our data suggest a progressive degenerative transsynaptic effect of PT stroke on CMF, which could be a morphological correlate of transcallosal disinhibition.     

Electrophysiological evidence for the presence of fibers in continuity between dorsal and ventrl roots in the cat

Action potentials were recorded from the L7 or S1 dorsal root of the cat following stimulation of the peripheral end of the cut ventral root of the same segment. Conversely, action potentials were also recorded from the ventral root while stimulating the peripheral end of the cut dorsal root. Based on the conduction velocities of 52 single fibers, one-third were Aδ-fibers and the remaining two-thirds belonged to the C-fiber category. These results suggest that there are both A- and C-fibers in continuity between the dorsal and the ventral root.     

Learning-related changes of brain activation in the visual ventral stream: an fMRI study of mirror reading skill

A previous neuroimaging study has indicated that the visual dorsal stream may contribute to accurate reading of mirror-reversed words. However, the role of the visual ventral stream in the learning of mirror reading skill remains ambiguous. In the present fMRI study, we investigated learning-related changes in brain activation in the visual ventral stream in a mirror reading task. Subjects participated in three successive runs of the mirror reading task, in each of which they were asked to read mirror-reversed words and normal words as accurately and as quickly as possible. The behavioral data for the mirror reading condition showed significant improvement in reaction time but not in performance accuracy across the three runs. The activation data showed different learning-associated patterns related to the right and left visual ventral streams. On the right side, activity related to the reading of mirror stimuli was significantly greater than that related to normal stimuli in the first run only, whereas on the left side it was greater in all runs. Additional correlation analysis between response time data and percentage signal changes only in the mirror reading condition showed significant correlation on the right visual ventral stream in the first run only, whereas that on the left visual ventral stream was found only in the third run. The dissociable response between the right and left visual ventral streams may reflect learning-related changes in reading strategy and may be critical in improving the speed of reading mirror-reversed words.