Association Fiber Systems Research Articles

Superior Longitudinal Fasciculus: A Review of the Anatomical Descriptions With Functional Correlates.

The superior longitudinal fasciculus (SLF) is part of the longitudinal association fiber system, which lays connections between the frontal lobe and other areas of the ipsilateral hemisphere. As a dominant association fiber bundle, it should correspond to a well-defined structure with a clear anatomical definition. However, this is not the case, and a lot of confusion and overlap surrounds this entity. In this review/opinion study, we survey relevant current literature on the topic and try to clarify the definition of SLF in each hemisphere. After a comparison of postmortem dissections and data obtained from diffusion MRI studies, we discuss the specifics of this bundle regarding its anatomical landmarks, differences in lateralization, as well as individual variability. We also discuss the confusion regarding the arcuate fasciculus in relation to the SLF. Finally, we recommend a nomenclature based on the findings exposed in this review and finalize with a discussion on relevant functional correlates of the structure.

Diffusion MRI data, sulcal anatomy, and tractography for eight species from the Primate Brain Bank

Large-scale comparative neuroscience requires data from many species and, ideally, at multiple levels of description. Here, we contribute to this endeavor by presenting diffusion and structural MRI data from eight primate species that have not or rarely been described in the literature. The selected samples from the Primate Brain Bank cover a prosimian, New and Old World monkeys, and a great ape. We present preliminary labelling of the cortical sulci and tractography of the optic radiation, dorsal part of the cingulum bundle, and dorsal parietal–frontal and ventral temporal-frontal longitudinal white matter tracts. Both dorsal and ventral association fiber systems could be observed in all samples, with the dorsal tracts occupying much less relative volume in the prosimian than in other species. We discuss the results in the context of known primate specializations and present hypotheses for further research. All data and results presented here are available online as a resource for the scientific community.

Magnetic Resonance Imaging of the Brains of Three Peramelemorphian Marsupials

Peramelemorphians (bandicoots and bilbies) are a unique and diverse group of digging Australasian marsupials, but their behavioral neurology and neuroanatomy is poorly known. Here, we have used Magnetic Resonance Imaging (MRI) to study the brains of three peramelemorphians: two bandicoots (Perameles nasuta and Isoodon obesulus) and the bilby (Macrotis lagotis), which is endangered. These brains had been stored in formaldehyde solution for more than 80 years and one of our goals was to demonstrate the feasibilty of extracting detailed comparative neuroanatomical information from the long-term preserved brains of rare, endangered, and extinct animals. High resolution anatomical and Diffusion Tensor Imaging was performed using a 9.4-T Bruker BioSpec 94/20 Avance III MRI system (Bruker, Ettlingen, Germany) located at the UNSW in Sydney. We were able to differentiate areal and laminar topography within isocortical areas (primary somatosensory – S1; and visual - V1, V2), as well as subdivisions within olfactory and limbic allocortical regions (cingulate, hippocampal). Resolution of subcortical structures was sufficient to differentiate α and β segments within the visual nucleus of the thalamus. We identified several previously unrecognized longitudinal association fiber systems as well as a rich array of sensory thalamocortical connections. Dense fiber pathways were observed to S1 and in the midbrain auditory pathways (mainly the lateral lemniscus, but also the brachium of the inferior colliculus). Our findings demonstrate the feasibility of using this sort of imaging of archived brains to analyze the neuroanatomy of rare and evolutionarily significant species and to relate these findings to the behavioral neurology of those species.

Illustrated Review of the Ventral Striatum's Olfactory Tubercle.

Modern neuroscience often relies upon artistic renderings to illustrate key aspects of anatomy. These renderings can be in 2 or even 3 dimensions. Three-dimensional renderings are especially helpful in conceptualizing highly complex aspects of neuroanatomy which otherwise are not visually apparent in 2 dimensions or even intact biological samples themselves. Here, we provide 3 dimensional renderings of the gross- and cellular-anatomy of the rodent olfactory tubercle. Based upon standing literature and detailed investigations into rat brain specimens, we created biologically inspired illustrations of the olfactory tubercle in 3 dimensions as well as its connectivity with olfactory bulb projection neurons, the piriform cortex association fiber system, and ventral pallidum medium spiny neurons. Together, we intend for these illustrations to serve as a resource to the neuroscience community in conceptualizing and discussing this highly complex and interconnected brain system with established roles in sensory processing and motivated behaviors.

Long-term plasticity in the regulation of olfactory bulb activity by centrifugal fibers from piriform cortex.

Olfactory bulb granule cells are activated synaptically via two main pathways. Mitral/tufted (M/T) cells form dendrodendritic synapses on granule cells that can be activated by antidromic stimulation of the lateral olfactory tract (LOT). Centrifugal fibers originating from the association fiber (AF) system in piriform cortex (PC) make axodendritic synapses on granule cells within the granule cell layer (GCL) that can be activated by orthodromic stimulation of AF axons in the PC. We explored functional plasticity in the AF pathway by recording extracellularly from individual M/T cells and presumed granule cells in male Long-Evans rats under urethane anesthesia while testing their response to LOT and AF stimulation. Presumed granule cells driven synaptically by LOT stimulation (type L cells) were concentrated in the superficial half of the GCL and were activated at short latencies, whereas those driven synaptically by AF stimulation (type A cells) were concentrated in the deep half of the GCL and were activated at longer latencies. Type A cells were readily detected only in animals in which the AF input to the GCL had been previously potentiated by repeated high-frequency stimulation. An additional bout of high-frequency stimulation administered under urethane caused an immediate increase in the number of action potentials evoked in type A cells by AF test stimulation and a concomitant increase in inhibition of M/T cells. These results underscore the importance of the role played in olfactory processing by PC regulation of OB activity and document the long-lasting potentiation of that regulation by repeated high-frequency AF activation.

A Major Role for Intracortical Circuits in the Strength and Tuning of Odor-Evoked Excitation in Olfactory Cortex

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons.

Differential potentiation of early and late components evoked in olfactory cortex by stimulation of cortical association fibers

The present study examined in detail the development and decay of potentiation induced in vivo by repeated high-frequency stimulation of cortical association fibers (AF) in piriform cortex (PC). Male Long–Evans rats with chronically-implanted stimulating and recording electrodes were administered potentiating AF stimulation (thirty 10-pulse 100-Hz trains) on 8 consecutive days, followed by a ninth administration after an 8-day layoff. The time course of potentiation was monitored by local field potentials evoked in the PC and olfactory bulb (OB) by 0.1 Hz single-pulse AF test stimulation before, during, and following each potentiating treatment. AF test stimulation evoked two distinct components in the PC, an early component (EC) and a late component (LC). High-frequency AF stimulation produced potentiation of each component, but with very different characteristics. EC potentiation consisted of a brief augmentation during each bout of potentiating stimulation that persisted < 2 min after the last high-frequency train and showed no cumulative effects following repeated induction across days. In contrast, LC potentiation developed gradually, requiring several daily potentiation treatments to reach maximum amplitude, and decayed more slowly each time it was induced. Furthermore, LC potentiation persisted in latent form for at least 8 days following its apparent decay and could be reinstated by repeated test stimulation that was without effect at the beginning of the experiment. Potentiation in the OB resembled LC potentiation in its characteristics, but with less latent potentiation. These results indicate that the potentiation reported here is distinctly different from the long-term potentiation previously demonstrated in vitro in the PC, and suggest that this potentiation represents an increase in excitability within the cortical association fiber system that can be stored in latent form and retrieved at a later time. These characteristics make this potentiation a suitable candidate for participation in long-term functional changes within olfactory cortex.

Retracted Article: Extent of nerve cell injury in Marmarou's model compared to other brain trauma models

We sought to determine the extent of nerve cell injury in the Marmarou's acceleration impact model of diffuse brain injury. Sensitive markers for cell injury including immunostaining for beta-amyloid precursor protein (beta-APP, a marker for diffuse axonal injury, DAI), Fluoro-Jade (FJ) histochemistry and electron microscopy (EM) were used in sham-operated and traumatized brains. APP immunostaining confirmed and extended previous findings of DAI in association and subcortical fiber systems in the white matter after injury. Increasing FJ labeling of neurons in layers II-III of sensorimotor cortex (smCx) from 4 to 48 hours after trauma and scattered labeled cells were found in the lower cortical layers. EM confirmed the presence of dystrophic pyramidal neurons in layers II-III of smCx 24 and 48 hours post-trauma. Taken together, the data revealed significant nerve cell injury without apparent cell death in this model.

Spatial and Temporal Distribution of Odorant-Evoked Activity in the Piriform Cortex

Despite a remarkably precise spatial representation of odorant stimuli in the early stages of olfactory processing, the projections to the olfactory (piriform) cortex are more diffuse and show characteristics of a combinatorial array, with extensive overlap of afferent inputs and widespread intracortical association connections. Furthermore, although there is increasing evidence for the importance of temporal structure in olfactory bulb odorant-evoked output, little is known about how this temporal patterning is translated within cortical neural ensembles. The present study used multichannel electrode arrays and paired single-unit recordings in rat anterior piriform cortex to test several predictions regarding ensemble coding in this system. The results indicate that odorants evoke activity in a spatially scattered ensemble of anterior piriform cortex neurons, and the ensemble activity includes a rich temporal structure. The most pronounced discrimination between different odorants by cortical ensembles occurs during the first inhalation of a 2 s stimulus. The distributed spatial and temporal structure of cortical activity is present at both global and local scales, with neighboring single units contributing to coding of different odorants and active at different phases of the respiratory cycle. Finally, cross-correlogram analyses suggest that cortical unit activity reflects not only afferent input from the olfactory bulb but also intrinsic activity within the intracortical association fiber system. These results provide direct evidence for predictions stemming from anatomical- and theoretical-based models of piriform cortex.

Model-Based Variational Smoothing and Segmentation for Diffusion Tensor Imaging in the Brain

This article applies a unified approach to variational smoothing and segmentation to brain diffusion tensor image data along user-selected attributes derived from the tensor, with the aim of extracting detailed brain structure information. The application of this framework simultaneously segments and denoises to produce edges and smoothed regions within the white matter of the brain that are relatively homogeneous with respect to the diffusion tensor attributes of choice. This approach enables the visualization of a smoothed, scale invariant representation of the tensor data field in a variety of diverse forms. In addition to known attributes such as fractional anisotropy, these representations include selected directional tensor components and additionally associated continuous valued edge fields that might be used for further segmentation. A comparison is presented of the results of three different data model selections with respect to their ability to resolve white matter structure. The resulting images are integrated to provide better perspective of the model properties (edges, smoothed image, and so forth) and their relationship to the underlying brain anatomy. The improvement in brain image quality is illustrated both qualitatively and quantitatively, and the robust performance of the algorithm in the presence of added noise is shown. Smoothing occurs without loss of edge features because of the simultaneous segmentation aspect of the variational approach, and the output enables better delineation of tensors representative of local and long-range association, projection, and commissural fiber systems.

Potentiation of late components in olfactory bulb and piriform cortex requires activation of cortical association fibers

Previous research has demonstrated that repeated high-frequency stimulation of the granule cell layer of the olfactory bulb (OB) produces an enduring potentiation of late components (PLC) in potentials evoked in the OB and piriform cortex (PC), while leaving the monosynaptic EPSP produced by OB mitral cells in PC pyramidal cells unaltered. Two experiments were conducted using male Long–Evans rats with chronically implanted electrodes to assess the relative contribution to this potentiation of the two main fiber systems that interconnect the OB and PC: the lateral olfactory tract (LOT), which contains mitral cell axons that synapse on PC pyramidal cells, and the PC association fiber system, which consists of the axons of PC pyramidal cells that synapse on several cell populations within the PC and on granule cells in the OB. The results indicate that stimulation of PC association fibers is both necessary and sufficient to duplicate the pattern of potentiation seen following OB stimulation in previous experiments. LOT stimulation had no consistent effect, and coactivation of the LOT and PC association fibers was no more effective than activation of PC association fibers alone. Possible mechanisms underlying this effect are discussed, including (1) long-term potentiation (LTP) at synapses made by the axons of PC pyramidal cells on neurons in the OB and PC; and (2) repetitive firing in PC pyramidal cells due to regenerative excitation in a population of deep cells in the PC and endopiriform nucleus.

Fiber system linking the mid-dorsolateral frontal cortex with the retrosplenial/presubicular region in the rhesus monkey

The present study investigated the origin, course, and terminations of the association fiber system linking the frontal cortex with the hippocampal system by means of the cingulum bundle. Injections of tritiated amino acids were placed within individual cytoarchitectonic areas of the frontal cortex in the rhesus monkey. It was demonstrated that the mid-dorsolateral frontal cortex (areas 46, 9/46, and 9) and its medial extension (medial areas 9 and 9/32) is the origin of a specific fiber pathway, running posteriorly as part of the cingulum bundle, and terminating mainly in the retrosplenial area 30 and the posterior presubiculum. This fiber bundle therefore provides the anatomical substrate of a functional interaction between the mid-dorsolateral frontal cortex and the hippocampal memory system for the monitoring of information within working memory.

Role of the net architecture in piriform cortex activity: analysis by a mathematical model.

We present a mathematical analysis of the piriform cortex activity in rats. Experimental data were obtained by means of optical recording of fluorescent signals driven by neuronal activity. From these data, we determined the numerical value of the relaxation time for the pyramidal cell activity in layers II and III and the time latency map for bulb activation. Our model for the piriform cortex is based on pairs of excitatory and inhibitory neurons which correspond to pyramidal cells of layers II and III and to their inhibitory associated interneurons respectively; pyramidal cells are also interconnected through short and long range association fiber systems. Under such conditions, the model outputs resemble closely the experimental observations: (1) a double-bumped response to a strong and short stimulation; (2) oscillatory behavior under weak sustained stimulation conditions; (3) propagation of traveling activity waves; and (4) pacemaker activity when clusters of neurons are preferentially coupled.

Intrinsic association fiber system of the piriform cortex: a quantitative study based on a cholera toxin B subunit tracing in the rat.

By using retrograde and anterograde transport of the B subunit of cholera toxin (CTb), we examined quantitatively the association fiber systems, i.e., the collaterals of pyramidal cell axons, that reciprocally connect both the rostral and the caudal parts of the piriform cortex (PC). Well-defined CTb injections were obtained in layers Ib or II-III of the rostral and the caudal parts of the PC. Using precision counting, we determined the proportion of cellular profiles in layers II and III that gave rise to association fibers and thus demonstrated a predominance of rostrocaudal fibers over the caudorostral ones. Our data also support a precise laminar organization of the PC in which the rostrocaudal fibers originated mainly from layer II and the caudorostral fibers primarily from layer III. Cholera toxin injections into layer Ib produced a peak of labeled profiles 2 mm from the site, indicating that a large proportion of the association fibers from layer II travel for at least 2 mm and then synapse in layer Ib. At either end of the PC, the association projections with respect to olfactory processing, propagation of the activity within the PC, and the possible role of intrinsic fibers in olfactory memory.

Intrinsic association fiber system of the piriform cortex: A quantitative study based on a cholera toxin B subunit tracing in the rat

Intrinsic association fiber system of the piriform cortex: A quantitative study based on a cholera toxin B subunit tracing in the rat

Associative long-term potentiation in piriform cortex slices requires GABAA blockade

Previous studies have demonstrated that NMDA-dependent, long-term potentiation (LTP) can be induced in both afferent and intrinsic association fiber systems in the piriform (primary olfactory) cortex. In this report we demonstrate that an associative form of LTP can be induced by coactivation of these two systems, which terminate on adjacent apical dendritic segments of pyramidal cells. Potentiating stimulus trains were delivered to either afferent or association fibers, and weak shocks, which were nonpotentiating when delivered alone, were delivered to the other pathway. Under control recording conditions where homosynaptic (single pathway) LTP is consistently evoked, coincident application of these stimuli failed to induce LTP of the weak shock response. However, after local blockade of the fast, GABAA-mediated IPSP, associative LTP was consistently produced in both directions. Induction was blocked by D-2-amino-5-phosphonovaleric acid, indicating that it is dependent on activation of NMDA receptors. It is speculated that afferent and association fibers are segregated on different dendritic segments of pyramidal cells in piriform cortex to allow regulation of associative LTP by way of centrifugal inputs that modulate the activity of GABAergic interneurons.

Membrane currents evoked by afferent fiber stimulation in rat piriform cortex. II. Analysis with a system model.

1. The detailed visualization of membrane currents over time and depth provided by current source-density (CSD) analysis was used as the basis for development of a system model that reproduces the response of piriform cortex to afferent fiber stimulation. This model has allowed the testing and substantial revision of previous hypotheses concerning the sequence of neuronal events underlying this response, has enabled net membrane currents visualized by CSD analysis to be separated into active and passive components, and has generated predictions for important axonal and synaptic parameters as well as for the behavior of piriform cortex as a system. 2. The model was developed in three steps. Activity in excitatory fiber systems was first represented with continuous distributions. The "population conductances" due to the activation of excitatory fiber systems were then computed from the distribution of action-potential arrival times and the conductance waveform for excitatory synapses. Finally, these temporally dispersed excitatory conductances and locally mediated inhibitory conductances were introduced at appropriate locations on a compartmentalized cable that simulated the passive response of the pyramidal cell population. 3. After the simulation of membrane currents at one site, all parameters in the model were fixed so that it could be used to predict the variation in the time course of membrane currents at additional recording sites; comparison with the results of CSD analysis at these sites provided the primary validation of the model. Additional validation included the simulation of membrane potentials derived by intracellular recording, including the effects of manipulating somatic potential with current injection. 4. Several conclusions have emerged from the mathematical description of activity in fiber systems. Propagation of activity in both afferent and association (corticocortical) fiber systems is "dispersive" as a result of a wide spectrum of axon conduction velocities. The characteristically different time courses of afferent and association fiber-mediated responses are largely determined by the focal, shock-evoked origin of the volley in afferent fibers as opposed to the spatially distributed disynaptic origin of activity in association fibers. Conduction velocity distributions for afferent and association fiber systems are skewed and can be approximated with lognormal distributions. 5. General solutions, which relate an arbitrary conduction velocity distribution to arrival time and spatial distributions of action potentials, were used to generate specific solutions describing the effects of dispersive propagation.(ABSTRACT TRUNCATED AT 400 WORDS)

NMDA-dependent induction of long-term potentiation in afferent and association fiber systems of piriform cortex in vitro

Long-term potentiation (LTP) was demonstrated in a slice preparation of piriform (olfactory) cortex. LTP could be reliably induced in both afferent and association fiber pathways. The magnitude of the observed potentiation was greater in the association fiber pathway. 2-Amino-5-phosphonovalerate (APV) blocked induction of LTP in both pathways, indicating thatN-methyl- d-aspartate (NMDA) receptor activation is required for induction.

Afferent and association fiber differences in short-term potentiation in piriform (olfactory) cortex of the rat

1. The effects of low-frequency stimulus trains on synaptically evoked responses in piriform cortex pyramidal cells were studied by the use of intracellular recording techniques in an in vitro slice preparation. Afferent and association fiber systems were differentially stimulated with electrodes placed in layer 1a or layer 1b, respectively. To quantify synapse modifiability, the heights of postsynaptic potentials (PSPs) elicited by paired-pulse stimulation (100-ms interval) were averaged over a 50-s period before and after a set of 10 stimulus trains (10 pulses each, 20 Hz, 5-s interpulse interval). 2. Afferent and association fibers showed consistent differences in their response to stimulation during the period lasting from approximately 10 to 200 s after presentation of trains. During this time period, the responses to stimulation of association fibers in layer 1b displayed a short-term potentiation, which over the 10 posttrain trials, produced an average increase in PSP height of 23.2 +/- 3.7% (mean +/- SE). On the other hand, responses to layer 1a stimulation showed an average depression of 10.9 +/- 3.6%. Layer 1b potentiation decayed with time constant roughly estimated at 79 s. Layer 1b potentiation appeared even at very low stimulus voltages and after local association fiber input had been cut, suggesting that it was largely a monosynaptic effect. 3. In the period immediately after train presentations, responses evoked by both layers showed a short-term augmentation with a time constant around 3 s. In layer 1a, this augmentation was superimposed on a depression with slow recovery. At longer times after train presentation (greater than 5 min), 2 cells out of 46 showed changes (increases) in synaptic efficacy in response to layer 1b stimulation. 4. In the current experiments both layers 1a and 1b showed statistically significant facilitation before the presentation of stimulus trains. However, layer 1b facilitation decreased from 22.7 +/- 3.5% to a statistically insignificant 3.9 +/- 3.3% after the presentation of trains, whereas layer 1a facilitation remained at a statistically significant level of 23.1 +/- 5.7%. 5. These experiments show that pyramidal cell responses to stimulation of the afferent and association fiber systems are affected differently by the previous presentation of trains of stimuli. This suggests that mechanisms of synaptic modification may differ between the afferent and intrinsic association synaptic projections onto single pyramidal cells in olfactory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution and ultrastructure of neurons in opossum piriform cortex displaying immunoreactivity to GABA and GAD and high-affinity tritiated GABA uptake.

GABAergic neurons have been identified in the piriform cortex of the opossum at light and electron microscopic levels by immunocytochemical localization of GABA and the GABA-synthesizing enzyme glutamic acid decarboxylase and by autoradiographic visualization of high-affinity 3H-GABA uptake. Four major neuron populations have been distinguished on the basis of soma size, shape, and segregation at specific depths and locations: large horizontal cells in layer Ia of the anterior piriform cortex, small globular cells with thin dendrites concentrated in layers Ib and II of the posterior piriform cortex, and multipolar and fusiform cells concentrated in the deep part of layer III in anterior and posterior parts of the piriform cortex and the subjacent endopiriform nucleus. All four populations were well visualized with both antisera, but the large layer Ia horizontal cells displayed only very light 3H-GABA uptake, thus suggesting a lack of local axon collaterals or lack of high-affinity GABA uptake sites. The large, ultrastructurally distinctive somata of layer Ia horizontal cells receive a very small number of symmetrical synapses; the thin, axonlike dendrites of small globular cells are exclusively postsynaptic and receive large numbers of both symmetrical and asymmetrical synapses, in contrast to somata which receive a small number of both types; and the deep multipolar and fusiform cells receive a highly variable number of symmetrical and asymmetrical synapses on somata and proximal dendrites. Labeled puncta of axon terminal dimensions were found in large numbers in the neuropil surrounding pyramidal cell somata in layer II and in the endopiriform nucleus. Moderately large numbers of labeled puncta were found in layer I at the depth of pyramidal cell apical dendrites with greater numbers in layer Ia at the depth of distal apical segments than in layer Ib. High-affinity GABA uptake was demonstrated in the termination zone of the projection from the anterior olfactory nucleus to the anterior piriform cortex. Cell bodies of origin of this projection displayed heavy retrograde labeling with 3H-GABA. Matching neuropil and cellular labeling was demonstrated with the GABA-BSA antiserum but not with the GAD antiserum, thus suggesting that GABA is normally present in these cells but is taken up from the neuropil rather than synthesized. No comparable high-affinity GABA uptake was demonstrated in the association fiber systems that originate in the piriform cortex.(ABSTRACT TRUNCATED AT 400 WORDS)