Connectivity of somatosensory cortical area 1 forms an anatomical substrate for the emergence of multifinger receptive fields and complex feature selectivity in the squirrel monkey (Saimiri sciureus)

Converging evidence shows that interaction of digit‐specific input, which is required to form global tactile percepts, begins as early as area 3b in the primary somatosensory cortex with the involvement of intrinsic lateral connections. How tactile processing is further elaborated in area 1, the next stage of the somatosensory cortical hierarchy, is less understood. This question was investigated by studying the tangential distribution of intrinsic and interareal connections of finger representations of area 1. Retrogradely labeled cell densities and anterogradely labeled fibers and terminal patches were plotted and quantified with respect to the hand representation by combining tract tracing with electrophysiological mapping and intrinsic signal optical imaging in somatosensory areas. Intrinsic connections of distal finger pad representations of area 1 spanned the representation of multiple digits indicating strong cross‐digit connectivity. Area 1 distal finger pad regions also established high‐density connections with homotopic regions of areas 3b and 2. Although similar to area 3b, connections of area 1 distributed more widely and covered a larger somatotopic representation including more proximal parts of the finger representations. The lateral connectivity pattern of area 1 is a suitable anatomical substrate of the emergence of multifinger receptive fields, complex feature selectivity, and invariant stimulus properties of the neurons. J. Comp. Neurol. 522:1769–1785, 2014. © 2013 Wiley Periodicals, Inc.     

Combining diffusion magnetic resonance tractography with stereology highlights increased cross‐cortical integration in primates

The isocortex of primates is disproportionately expanded relative to many other mammals, yet little is known about what the expansion of the isocortex entails for differences in cellular composition and connectivity patterns in primates. Across the depth of the isocortex, neurons exhibit stereotypical patterns of projections. Upper‐layer neurons (i.e., layers II–IV) project within and across cortical areas, whereas many lower‐layer pyramidal neurons (i.e., layers V–VI) favor connections to subcortical regions. To identify evolutionary changes in connectivity patterns, we quantified upper (i.e., layers II–IV)‐ and lower (i.e., layers V–VI)‐layer neuron numbers in primates and other mammals such as rodents and carnivores. We also used MR tractography based on high‐angular resolution diffusion imaging and diffusion spectrum imaging to compare anterior‐to‐posterior corticocortical tracts between primates and other mammals. We found that primates possess disproportionately more upper‐layer neurons as well as an expansion of anterior‐to‐posterior corticocortical tracts compared with other mammals. Taken together, these findings demonstrate that primates deviate from other mammals in exhibiting increased cross‐cortical connectivity. J. Comp. Neurol. 525:1075–1093, 2017. © 2016 Wiley Periodicals, Inc.     

Developmental remodeling of corticocortical feedback circuits in ferret visual cortex

Visual cortical areas in the mammalian brain are linked through a system of interareal feedforward and feedback connections, which presumably underlie different visual functions. We characterized the refinement of feedback projections to primary visual cortex (V1) from multiple sources in juvenile ferrets ranging in age from 4–10 weeks postnatal. We studied whether the refinement of different aspects of feedback circuitry from multiple visual cortical areas proceeds at a similar rate in all areas. We injected the neuronal tracer cholera toxin B (CTb) into V1 and mapped the areal and laminar distribution of retrogradely labeled cells in extrastriate cortex. Around the time of eye opening at 4 weeks postnatal, the retinotopic arrangement of feedback appears essentially adult‐like; however, suprasylvian cortex supplies the greatest proportion of feedback, whereas area 18 supplies the greatest proportion in the adult. The density of feedback cells and the ratio of supragranular/infragranular feedback contribution declined in this period at a similar rate in all cortical areas. We also found significant feedback to V1 from layer IV of all extrastriate areas. The regularity of cell spacing, the proportion of feedback arising from layer IV, and the tangential extent of feedback in each area all remained essentially unchanged during this period, except for the infragranular feedback source in area 18, which expanded. Thus, while much of the basic pattern of cortical feedback to V1 is present before eye opening, there is major synchronous reorganization after eye opening, suggesting a crucial role for visual experience in this remodeling process. J. Comp. Neurol. 522:3208–3228, 2014. © 2014 Wiley Periodicals, Inc.     

The organization of frontoparietal cortex in the tree shrew (Tupaia belangeri): II. Connectional evidence for a frontal-posterior parietal network

Tree shrews are small squirrel-like mammals that are the closest living relative to primates available for detailed neurobiological study. In a recent study (Remple et al. [2006] J. Comp. Neurol. 497:133-154), we provided anatomical and electrophysiological evidence that the frontoparietal cortex of tree shrews has two motor fields (M1 and M2) and five somatosensory fields (3a, 3b, S2, somatosensory caudal area [SC], and parietal ventral area [PV]). In the present study, we injected anatomical tracers into M1, M2, 3a, 3b, SC, and posterior parietal cortex to establish the ipsilateral cortical connections of these areas. The results provide evidence for a number of new cortical areas including medial motor and somatosensory areas (MMA and MSA), three posterior parietal areas (PPd, PPv, and PPc), and an area ventral to temporal inferior cortex (TIV). Ml receives topographic projections from M2, MMA, 3a, and PPv, and nontopographic connections from the temporal anterior and dorsal areas (TA and TD), PPc, TIV, and MSA. The connections of M2 are similar to those of M1, except that M2 receives denser projections from TIV, PPc, and dorsal frontal cortex and sparser input from M1. Areas 3a, 3b, and SC receive dense topographic projections from each other, S2, and PV and sparser connections from PPd and PPv. Area 3a receives additional input from posterior parietal and temporal regions and from M1 and MMA. Overall, the frontoparietal connections of tree shrew cortex are most similar to those of prosimian primates and quite different from those of more distant relatives such as rats.     

Alterations in cortical and thalamic connections of somatosensory cortex following early loss of vision

Early loss of vision produces dramatic changes in the functional organization and connectivity of the neocortex in cortical areas that normally process visual inputs, such as the primary and second visual area. This loss also results in alterations in the size, functional organization, and neural response properties of the primary somatosensory area, S1. However, the anatomical substrate for these functional changes in S1 has never been described. In the present investigation, we quantified the cortical and subcortical connections of S1 in animals that were bilaterally enucleated very early in development, prior to the formation of retino-geniculate and thalamocortical pathways. We found that S1 receives dense inputs from novel cortical fields, and that the density of existing cortical and thalamocortical connections was altered. Our results demonstrate that sensory systems develop in tandem and that alterations in sensory input in one system can affect the connections and organization of other sensory systems. Thus, therapeutic intervention following early loss of vision should focus not only on restoring vision, but also on augmenting the natural plasticity of the spared systems.     

Differential innervation within a transverse plane of spinal gray matter by sensorimotor cortices,with special reference to the somatosensory cortices

The corticospinal (CS) neurons projecting to the cervical cord distribute not only in motor-related cortical areas, but also in somatosensory areas, including the primary somatosensory cortex (S1). The exact functions of these widely distributed CS neurons are largely unknown, however. In this study, we injected mice with adeno-associated virus encoding membrane-binding fluorescent proteins to investigate the distribution of axons from CS neurons in different regions within a broad cortical area. We found that CS axons from the primary motor cortex (M1), the rostral part of S1 (S1r), and the caudal part of S1 (S1c) differentially project to specific compartments within the spinal gray matter of the seventh cervical cord segment: (a) M1 projects mainly to intermediate and ventral areas, (b) S1r to the mediodorsal area, and (c) S1c to the dorsolateral area. We also found that the projection from S1r, which corresponds to the forelimb area, largely overlaps the cutaneous afferent terminals from the forepaw (hand) in the dorsal horn, and we detected a similar relation between S1c and the trunk. Our findings suggest the existence of considerably fine somatotopic compartments within the dorsal horn that process somatosensation and descending information, which is provided mainly by S1 CS neurons and contribute to delicate control of sensory information in generation of movement.     

The small world of the cerebral cortex

While much information is available on the structural connectivity of the cerebral cortex, especially in the primate, the main organizational principles of the connection patterns linking brain areas, columns and individual cells have remained elusive. We attempt to characterize a wide variety of cortical connectivity data sets using a specific set of graph theory methods. We measure global aspects of cortical graphs including the abundance of small structural motifs such as cycles, the degree of local clustering of connections and the average path length. We examine large-scale cortical connection matrices obtained from neuroanatomical data bases, as well as probabilistic connection matrices at the level of small cortical neuronal populations linked by intra-areal and interareal connections. All cortical connection matrices examined in this study exhibit “small-world” attributes, characterized by the presence of abundant clustering of connections combined with short average distances between neuronal elements. We discuss the significance of these universal organizational features of cortex in light of functional brain anatomy. Supplementary materials are at www.indiana.edu/∼cortex/lab.htm.     

Segregated fronto‐cortical and midbrain connections in the mouse and their relation to approach and avoidance orienting behaviors

The orchestration of orienting behaviors requires the interaction of many cortical and subcortical areas, for example the superior colliculus (SC), as well as prefrontal areas responsible for top–down control. Orienting involves different behaviors, such as approach and avoidance. In the rat, these behaviors are at least partially mapped onto different SC subdomains, the lateral (SCl) and medial (SCm), respectively. To delineate the circuitry involved in the two types of orienting behavior in mice, we injected retrograde tracer into the intermediate and deep layers of the SCm and SCl, and thereby determined the main input structures to these subdomains. Overall the SCm receives larger numbers of afferents compared to the SCl. The prefrontal cingulate area (Cg), visual, oculomotor, and auditory areas provide strong input to the SCm, while prefrontal motor area 2 (M2), and somatosensory areas provide strong input to the SCl. The prefrontal areas Cg and M2 in turn connect to different cortical and subcortical areas, as determined by anterograde tract tracing. Even though connectivity pattern often overlap, our labeling approaches identified segregated neural circuits involving SCm, Cg, secondary visual cortices, auditory areas, and the dysgranular retrospenial cortex likely to be involved in avoidance behaviors. Conversely, SCl, M2, somatosensory cortex, and the granular retrospenial cortex comprise a network likely involved in approach/appetitive behaviors.     

Morphological heterogeneity among corticogeniculate neurons in ferrets: quantification and comparison with a previous report in macaque monkeys

The corticogeniculate (CG) pathway links the visual cortex with the lateral geniculate nucleus (LGN) of the thalamus and is the first feedback connection in the mammalian visual system. Whether functional connections between CG neurons and LGN relay neurons obey or ignore the separation of feedforward visual signals into parallel processing streams is not known. Accordingly, there is some debate about whether CG neurons are morphologically heterogeneous or homogenous. Here we characterized the morphology of CG neurons in the ferret, a visual carnivore with distinct feedforward parallel processing streams, and compared the morphology of ferret CG neurons with CG neuronal morphology previously described in macaque monkeys [Briggs et al. (2016) Neuron, 90, 388]. We used a G-deleted rabies virus as a retrograde tracer to label CG neurons in adult ferrets. We then reconstructed complete dendritic morphologies for a large sample of virus-labeled CG neurons. Quantification of CG morphology revealed three distinct CG neuronal subtypes with striking similarities to the CG neuronal subtypes observed in macaques. These findings suggest that CG neurons may be morphologically diverse in a variety of highly visual mammals in which feedforward visual pathways are organized into parallel processing streams. Accordingly, these results provide support for the notion that CG feedback is functionally parallel stream-specific in ferrets and macaques.     

Functional connectivity with cortical depth assessed by resting state fMRI of subregions of S1 in squirrel monkeys

Whereas resting state blood oxygenation‐level dependent (BOLD) functional MRI has been widely used to assess functional connectivity between cortical regions, the laminar specificity of such measures is poorly understood. This study aims to determine: (a) whether the resting state functional connectivity (rsFC) between two functionally related cortical regions varies with cortical depth, (b) the relationship between layer‐resolved tactile stimulus‐evoked activation pattern and interlayer rsFC pattern between two functionally distinct but related somatosensory areas 3b and 1, and (c) the effects of spatial resolution on rsFC measures. We examined the interlayer rsFC between areas 3b and 1 of squirrel monkeys under anesthesia using tactile stimulus‐driven and resting state BOLD acquisitions at submillimeter resolution. Consistent with previous observations in the areas 3b and 1, we detected robust stimulus‐evoked BOLD activations with foci were confined mainly to the upper layers (centered at 21% of the cortical depth). By carefully placing seeds in upper, middle, and lower layers of areas 3b and 1, we observed strong rsFC between upper and middle layers of these two areas. The layer‐resolved activation patterns in areas 3b and 1 agree with their interlayer rsFC patterns, and are consistent with the known anatomical connections between layers. In summary, using BOLD rsFC pattern, we identified an interlayer interareal microcircuit that shows strong intrinsic functional connections between upper and middle layer areas 3b and 1. RsFC can be used as a robust invasive tool to probe interlayer corticocortical microcircuits.     

Cell type specific impact of cannabinoid receptor signaling in somatosensory barrel map formation in mice

Endocannabinoids and their receptors are highly abundant in the developing cerebral cortex and play major roles in early developmental processes, for example, neuronal proliferation, migration, and axonal guidance as well as postnatal plasticity. To investigate the role of the cannabinoid type 1 receptor (CB1) in the formation of sensory maps in the cerebral cortex, the topographic representation of the whiskers in the primary somatosensory cortex (barrel field) of adult mice with different cell type specific genetic deletion of CB1 was studied. A constitutive absence of CB1 (CB1-KO) significantly decreased the total area of the somatosensory cortical map, affecting barrel, and septal areas. Cell specific CB1 deletion in dorsal telencephalic glutamatergic neurons only (Glu-CB1-KO) or in both glutamatergic and forebrain GABAergic neurons (Glu/GABA-CB1-KO) resulted in an increased septa area in the barrel field map. No significant modifications in area parameters could be observed in GABA-CB1-KO mice. These data demonstrate that CB1 signaling especially in cortical glutamatergic neurons is essential for the development of topographic maps in the cerebral cortex.     

Differential dose responses of transcranial focused ultrasound at brain regions indicate causal interactions

We have previously shown that focused ultrasound (FUS) pulses in low pressure range exerted bidirectional and brain state-dependent neuromodulation in the nonhuman primate somatosensory cortices by fMRI. Here we aim to gain insights about the proposed neuron selective modulation of FUS and probe feedforward versus feedback interactions by simultaneously quantifying the stimulus (FUS pressures: 925, 425, 250 kPa) and response (% BOLD fMRI changes) function at the targeted area 3a/3b and off-target cortical areas at 7T. In resting-state, lowered intensities of FUS resulted in decreased fMRI signal changes at the target area 3a/3b and off-target area 1/2, S2, MCC, insula and auditory cortex, and no signal difference in thalamic VPL and MD nuclei. In activated states, concurrent high-intensity FUS significantly enhanced touch-evoked signals in area 1/2. Medium- and low-intensity FUS significantly suppressed touch-evoked BOLD signals in all areas except in the auditory cortex, VPL and MD thalamic nuclei. Distinct state dependent and dose-response curves led us to hypothesize that FUS's neuromodulatory effects may be mediated through preferential activation of different populations of neurons. Area 3a/3b may have distinct causal feedforward and feedback interactions with Area 1/2, S2, MCC, insula, and VPL. FUS offers a noninvasive neural stimulation tool for dissecting brain circuits and probing causal functional connections.     

A logical relationship for schizophrenia,bipolar, and major depressive disorder. Part 4: Evidence from chromosome 4 high-density association screen

Convergent evidence from genetics, symptomatology, and psychopharmacology imply that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD). Familial clustering of SCZ, BPD, and MDD was systematically investigated [Aukes et al. (2012); Genetics in Medicine 14(3): 338–341], and any two or even three of these disorders could co-exist in some families. A total of 56,134 SNPs on chromosome 4 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (Type-I), 177 MDD patients, and 1,000 controls in a relative homogenous population in China. Susceptibility genes on chromosome 4 for the three major psychiatric disorders were systematically identified including outstanding genes (CXCL13, FSTL5, GLRB, KCNIP4, LPHN3, MAPK10, NPFFR2, NSUN7, PCDH10, PCDH7, PPA2, PPARGC1A, SCD5, SCFD2, and UNC5C). Unexpectedly, flanking genes for up to 93.67% of the associated SNPs were also confirmed in an enlarged cohort of 986 SCZ patients. Taken all relevant evidence together, our chromosome 4 results implicate that both of bipolar and major depressive disorders might be subtypes of SCZ rather than independent disease entity. Furthermore, similar evidence was also observed on chromosome 3, 5, 6, 7, and 8 [2018; The Journal of Comparative Neurology 526(1):59–79; Chen et al. (2017); American Journal of Translational Research 9(5):2473–2491; Chen et al. (2016); Current Molecular Medicine, 16(9):840–854; Chen et al. (2015); Behavioural Brain Research, 293:241–51; Chen et al. (2016); Molecular Neurobiology, 54(8):5868–5882].     

A logical relationship for schizophrenia,bipolar, and major depressive disorder. Part 1: Evidence from chromosome 1 high density association screen

Familial clustering of schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD) was investigated systematically (Aukes et al., Genetics in Medicine, 2012, 14, 338–341) and any two or even three of these disorders could coexist in some families. Furthermore, evidence from symptomatology and psychopharmacology also imply the existence of intrinsic connections between these three major psychiatric disorders. A total of 71,445 SNPs on chromosome 1 were genotyped on 119 SCZ, 253 BPD (type-I), 177 MDD cases and 1000 controls and further validated in 986 SCZ patients in the population of Shandong province of China. Outstanding psychosis genes are systematically revealed( ATP1A4, ELTD1, FAM5C, HHAT, KIF26B, LMX1A, NEGR1, NFIA, NR5A2, NTNG1, PAPPA2, PDE4B, PEX14, RYR2, SYT6, TGFBR3, TTLL7, and USH2A). Unexpectedly, flanking genes for up to 97.09% of the associated SNPs were also replicated in an enlarged cohort of 986 SCZ patients. F rom the perspective of etiological rather than clinical psychiatry, bipolar, and major depressive disorder could be subtypes of schizophrenia. Meanwhile, the varied clinical feature and prognosis might be the result of interaction of genetics and epigenetics, for example, irreversible or reversible shut down, and over or insufficient expression of certain genes, which may gives other aspects of these severe mental disorders.     

Ipsilateral intracortical connections of physiologically defined cutaneous representations in areas 3b and 1 of macaque monkeys: Projections in the vicinity of the central sulcus

This study examined cortical connections of areas 3b and 1 in 17 macaque monkeys in reference to regional somatotopography. The fluorescent retrograde tracers Fast Blue and Diamidino Yellow and the anterograde tracer Rhodamine Dextran were injected into closely related cutaneously responsive sites in primary somatosensory cortex, e. g., adjacent digits. Supra- and infragranular layers in nearly all studied areas contained labeled pyramidal cells. Labeled infragranular cells predominated at the fringes of a distribution where cells labeled from different tracer injections in the same brain intermixed more. All topographical regions across area 1 have reciprocal connections with areas 4, 3a, 3b, 1, 2, and 5. Intrinsic connections within area 1 and between it and area 2 are greatest; those with area 3b are less. Intrinsic connections within area 3b exceed all other nearby projections from this area which reciprocally connects with areas 3a, 1 and 2. Connections appear topographically organized, including those with poorly mapped regions, like area 5. These connections link representations of neighboring skin and skip map regions that include disjoint dermatomal areas. Connections from adjacent digit representations overlap; however, double-labeled cells were not found. Distal and proximal digit zones mostly interconnect within an area. Intrinsic connections spread further in area 1 than in area 3b, thereby joining more disparate topographical zones than interareal connections, which project more homotopically. The domain over which the map in somatosensory cortical area I (SI) dynamically changes following in tracortical microstimulation (Recanzone, Merzenich and Dinse, Cerebral Cortex 2:181-196, 1992) may depend on the range of intrinsic connections observed in this study. The extent of connections between cortical areas was less than expected and this challenges the hypothesis that these connections directly create receptive field enlargements.     

Early postnatal gene expression in the developing neocortex of prairie voles (Microtus ochrogaster) is related to parental rearing style

The earliest and most prevalent sensory experience includes tactile, thermal, and olfactory stimulation delivered to the young via contact with the mother, and in some mammals, the father. Prairie voles (Microtus ochrogaster), like humans, are biparental and serve as a model for understanding the impact of parent/offspring interactions on the developing brain. Prairie voles also exhibit natural variation in the level of tactile stimulation delivered by the parents to the offspring, and this has been well documented and quantified. Previous studies revealed that adult prairie vole offspring who received either high (HC) or low (LC) tactile contact from their parents have differences in the size of cortical fields and the connections of somatosensory cortex. In the current investigation, we examined gene expression, intraneocortical connectivity, and cortical thickness in newborn voles to appreciate when differences in HC and LC offspring begin to emerge. We observed differences in developmentally regulated genes, as well as variation in prelimbic and anterior cingulate cortical thickness at postnatal Day 1 (P1) in HC and LC voles. Results from this study suggest that parenting styles, such as those involving high or low physical contact, impact the developing neocortex via very early sensory experience as well as differences in epigenetic modifications that may emerge in HC and LC voles.     

Somatosensory cortex of prosimian Galagos: physiological recording,cytoarchitecture, and corticocortical connections of anterior parietal cortex and cortex of the lateral sulcus

Compared with our growing understanding of the organization of somatosensory cortex in monkeys, little is known about prosimian primates, a major branch of primate evolution that diverged from anthropoid primates some 60 million years ago. Here we describe extensive results obtained from an African prosimian, Galago garnetti. Microelectrodes were used to record from large numbers of cortical sites in order to reveal regions of responsiveness to cutaneous stimuli and patterns of somatotopic organization. Injections of one to several distinguishable tracers were placed at physiologically identified sites in four different cortical areas to label corticortical connections. Both types of results were related to cortical architecture. Three systematic representations of cutaneous receptors were revealed by the microelectrode recordings, S1 proper or area 3b, S2, and the parietal ventral area (PV), as described in monkeys. Strips of cortex rostral (presumptive area 3a) and caudal (presumptive area 1-2) to area 3b responded poorly to tactile stimuli in anesthetized galagos, but connection patterns with area 3b indicated that parallel somatosensory representations exist in both of these regions. Area 3b also interconnected somatotopically with areas S2 and PV. Areas S2 and PV had connections with areas 3a, 3b, 1-2, each other, other regions of the lateral sulcus, motor cortex (M1), cingulate cortex, frontal cortex, orbital cortex, and inferior parietal cortex. Connection patterns and recordings provided evidence for several additional fields in the lateral sulcus, including a retroinsular area (Ri), a parietal rostral area (PR), and a ventral somatosensory area (VS). Galagos appear to have retained an ancestral preprimate arrangement of five basic areas (S1 proper, 3a, 1-2, S2, and PV). Some of the additional areas suggested for lateral parietal cortex may be primate specializations.     

Mapping the avian visual tectofugal pathway using 3D reconstruction

Image processing in amniotes is usually accomplished by the thalamofugal and/or tectofugal visual systems. In laterally eyed birds, the tectofugal system dominates with functions such as color and motion processing, spatial orientation, stimulus identification, and localization. This makes it a critical system for complex avian behavior. Here, the brains of chicks, Gallus gallus, were used to produce serial brain sections in either coronal, sagittal, or horizontal planes and stained with either Nissl and Gallyas silver myelin or Luxol fast blue stain and cresyl echt violet (CEV). The emerging techniques of diffusible iodine-based contrast-enhanced computed tomography (diceCT) coupled with serial histochemistry in three planes were used to generate a comprehensive three-dimensional (3D) model of the avian tectofugal visual system. This enabled the 3D reconstruction of tectofugal circuits, including the three primary neuronal projections. Specifically, major components of the system included four regions of the retina, layers of the optic tectum, subdivisions of the nucleus rotundus in the thalamus, the entopallium in the forebrain, and supplementary components connecting into or out of this major avian visual sensory system. The resulting 3D model enabled a better understanding of the structural components and connectivity of this complex system by providing a complete spatial organization that occupied several distinct brain regions. We demonstrate how pairing diceCT with traditional histochemistry is an effective means to improve the understanding of, and thereby should generate insights into, anatomical and functional properties of complicated neural pathways, and we recommend this approach to clarify enigmatic properties of these pathways.     

Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey

The excitatory glutamatergic synapse is the principal site of communication between cortical pyramidal neurons and their targets, a key locus of action of many drugs, and highly vulnerable to dysfunction and loss in neurodegenerative disease. A detailed knowledge of the structure of these synapses in distinct cortical areas and across species is a prerequisite for understanding the anatomical underpinnings of cortical specialization and, potentially, selective vulnerability in neurological disorders. We used serial electron microscopy to assess the ultrastructural features of excitatory (asymmetric) synapses in the layers 2–3 (L2–3) neuropil of visual (V1) and frontal (FC) cortices of the adult mouse and compared findings to those in the rhesus monkey (V1 and lateral prefrontal cortex [LPFC]). Analyses of multiple ultrastructural variables revealed four organizational features. First, the density of asymmetric synapses does not differ between frontal and visual cortices in either species, but is significantly higher in mouse than in monkey. Second, the structural properties of asymmetric synapses in mouse V1 and FC are nearly identical, by stark contrast to the significant differences seen between monkey V1 and LPFC. Third, while the structural features of postsynaptic entities in mouse and monkey V1 do not differ, the size of presynaptic boutons are significantly larger in monkey V1. Fourth, both presynaptic and postsynaptic entities are significantly smaller in the mouse FC than in the monkey LPFC. The diversity of synaptic ultrastructural features demonstrated here have broad implications for the nature and efficacy of glutamatergic signaling in distinct cortical areas within and across species.     

Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule

The anatomical and functional organization of the inferior parietal lobule was investigated in macaque monkeys by using anterograde and retrograde anatomical tracing techniques and single cell recording techniques in awake, behaving monkeys. The connections of areas 7a and 7b, and of two previously unexplored areas, the lateral intraparietal area (LIP) and the dorsal prelunate area (DP), were examined in detail. Functional mapping experiments were performed in all four areas. Prior to this study the pathways for visual input to area 7a were unclear. In these experiments we found several direct projections from extrastriate visual areas, including the lateral intraparietal (LIP), dorsal prelunate (DP), parieto-occipital (PO), and medial superior temporal (MST) areas into area 7a. Using the observed laminar patterns of connections between areas 7a, LIP, and DP and other extrastriate cortical areas, we were able to construct a hypothetical flow of visual information processing from striate cortex to area 7a. A broader hierarchy was also produced, which relates the positions of areas 7a, 7b, LIP, and DP to various cortical fields in the parietal, temporal, and frontal lobes. By combining single cell recording techniques in trained monkeys with anatomical tracing techniques, we have parceled the inferior parietal lobule into several subdivisions on the basis of both anatomical and physiological grounds. A clear segregation of visual and somatosensory responses was found in the inferior parietal lobule with areas 7a, LIP, and DP being visual and visual-motor and area 7b being primarily somatosensory. A similar segregation was found anatomically with areas 7a, LIP, and DP being interconnected primarily with other visual cortical areas and area 7b being connected with several somatosensory areas. Area 7b was also found to connect to a few visual cortical areas, and these connections likely account for the small but consistent number of visually responsive cells that are found in this region. Areas LIP, DP, and 7a differed in receptive field and saccade-related properties. Area 7a visual receptive fields were very large and usually bilateral with a small but significant number of them having receptive field centers in the ipsilateral visual field. Area DP and LIP receptive fields were smaller and the receptive field peaks were almost always confined to the contralateral visual field. Areas 7a, DP, and LIP all contained cells with saccade-related responses; however, in area 7a there were fewer saccade cells than area LIP, and presaccadic responses were only observed in area LIP.(ABSTRACT TRUNCATED AT 400 WORDS)