Efferent connections of the prelimbic (area 32) and the infralimbic (area 25) cortices: an anterograde tracing study in the cat

The projections from the caudal part of the medial frontal cortex, encompassing the prelimbic area (PL) and the infralimbic area (IL) (Brodmann's areas 32 and 25, respectively), were studied in the cat with the anterograde autoradiographic tracing technique. The results indicate that the projection fields of IL, in contrast to those of PL, are restricted almost exclusively to limbic structures. Whereas the major thalamic projections from PL reach the mediodorsal, anteromedial, and ventromedial nuclei, the medial part of the lateral posterior nucleus, and the parataenial and reticular nuclei, and weak projections from this area are directed to the nucleus reuniens and other midline nuclei, the nucleus reuniens is the major thalamic termination field of fibers arising from IL. Cortical areas that are reached by fibers originating in PL and, to a lesser degree, also in IL, include more rostral prefrontal areas (areas 8, 6, and 12), the agranular insular, and the rostral perirhinal cortices. In contrast, cortical areas that are more strongly related to IL include the cingulate, retrosplenial, caudal entorhinal, and perirhinal cortices and the subiculum of the hippocampal formation. Another prominent output of PL concerns projections to an extensive medial part of the caudate nucleus and the ventral striatum, whereas fibers from IL only distribute most ventrally in the striatum. In the amygdaloid complex, fibers from PL were found to reach the basolateral, basomedial, and central nuclei, and fibers from IL to distribute to the medial and central nuclei. PL furthermore projects to the claustrum and the endopiriform nucleus. Other structures in the basal forebrain, including the medial septum, the nuclei of the diagonal band, the preoptic area, and the lateral and dorsal hypothalamus are densely innervated by IL and only sparsely by PL. With respect to more caudal parts of the brainstem, projections from PL and IL appeared to be essentially similar. They reach the ventral tegmental area, the periaqueductal gray, the parabrachial nucleus, and in cases of PL injections were followed as far caudally as the pons.     

Connections of the parahippocampal cortex. I. Cortical afferents

In the present study in the cat the parahippocampal cortex denotes the caudoventral part of the limbic lobe and is composed of the entorhinal and perirhinal cortices. The cytoarchitecture of these areas and their borders with adjacent cortical areas are briefly discussed. The organization of the cortical afferents of the parahippocampal cortex was studied with the aid of retrograde and anterograde tracing techniques. In order to identify the source of cortical afferents, injections of retrograde tracers such as wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP), or the fluorescent substances fast blue or nuclear yellow, were placed in different parts of the parahippocampal cortex. In an attempt to further disclose the topographical and laminar organization of the afferent pathways, injections of tritiated amino acids were placed in cortical areas that were found to project to the parahippocampal cortex. The results of these experiments indicate that fibers from olfactory-related areas, the hippocampus, and other parts of the limbic cortex project only to the entorhinal cortex. The afferents from olfactory structures terminate predominantly superficially, whereas hippocampal and limbic cortical afferents are directed mainly to layers deep to the lamina dissecans. Paralimbic areas, including the anterior cingulate and the prelimbic cortices on the medial aspect, and the orbitofrontal and granular and agranular insular cortices on the lateral aspect of the hemisphere, project to the entorhinal cortex and medial parts of area 35 of the perirhinal cortex. These mostly mesocortical afferents terminate in both the superficial and deep layers of the entorhinal and perirhinal cortices. Parasensory association areas, which form part of the neocortex, do not project farther medially in the parahippocampal cortex than the perirhinal areas 35 and 36. These afferents mainly stem from a rather wide rim of neocortex that lies directly adjacent to area 36 and extends from the posterior sylvian gyrus via the posterior ectosylvian gyrus into the posterior suprasylvian gyrus. There is a rostrocaudal topographical arrangement in these projections such that rostral cortical areas distribute more rostrally and caudal parts project to more caudal parts of the perirhinal cortex. The cortex of the posterior suprasylvian gyrus contains the paravisual areas 20 and 21. The posterior sylvian gyrus most probably represents a para-auditory association area, whereas the most ventral part of the posterior ectosylvian gyrus may constitute a convergence area for visual and auditory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)     

EphA4 has distinct functionality from EphA7 in the corticothalamic system during mouse brain development

Deciphering the molecular basis for guiding specific aspects of neocortical development remains a challenge because of the complexity of histogenic events and the vast array of protein interactions mediating these events. The Eph family of receptor tyrosine kinases is implicated in a number of neurodevelopmental activities. Eph receptors have been known to be capable of responding to several ephrin ligands within their subgroups, often eliciting similar downstream effects. However, several recent studies have indicated specificity between receptor–ligand pairs within each subfamily, the functional relevance of which is not defined. Here we show that a receptor of the EphA subfamily, EphA4, has effects distinct from those of its close relative, EphA7, in the developing brain. Both EphA4 and EphA7 interact similarly with corresponding ligands expressed in the developing neocortex. However, only EphA7 shows strong interaction with ligands in the somatosensory thalamic nuclei; EphA4 affects only cortical neuronal migration, with no visible effects on the guidance of corticothalamic (CT) axons, whereas EphA7 affects both cortical neuronal migration and CT axon guidance. Our data provide new evidence that Eph receptors in the same subfamily are not simply interchangeable but are functionally specified through selective interactions with distinct ligands in vivo. J. Comp. Neurol. 524:2080–2092, 2016. © 2015 Wiley Periodicals, Inc.     

D1 and D2 Receptor Gene Expression in the Rat Frontal Cortex: Cellular Localization in Different Classes of Efferent Neurons

The dopaminergic input to the frontal cortex has an important role in motor and cognitive functions. These effects are mediated by dopamine receptors both of type D1 and of type D2, although the neural circuits involved are not completely understood. We used in situ hybridization to determine the cellular localization of D1 and D2 receptor mRNAs in the rat frontal cortex. Retrograde tracing was used in the same animals to identify the main cortical efferent populations. Fluorogold was injected into the different cortical targets of the frontal cortex and sections were hybridized with D1 and D2 ³⁵S-labelled cRNA probes. D1 and D2 mRNA-containing neurons were present in all the cortical areas investigated, with greater expression in the medial prefrontal, insular and cingulate cortexes and lower expression in the motor and parietal cortexes. Neurons containing D1 mRNA were most abundant in layer Vlb; they were also present in layers Vla and V of all cortical layers and in layer II of the medial prefrontal, cingulate and insular areas. Double labelling with fluorogold demonstrated that D1 mRNA was present in corticocortical, corticothalamic and corticostriatal neurons. Neurons containing D2 mRNA were essentially restricted to layer V, but only in corticostriatal and corticocortical neurons. Neither D1 nor D2 mRNA was found in corticospinal or corticopontine neurons. The present results demonstrate that D1 and D2 receptor genes are expressed in efferent cortical populations, with higher expression for D1. In spite of an overlap in some cortical layers, the expression of D1 and D2 receptor genes is specific for different categories of pyramidal neurons.     

Efferent projections from limbic cortex of the temporal pole to the magnocellular medial dorsal nucleus in the rhesus monkey

The efferent projection from the rostral cortices of the temporal lobe to the magnocellular division of the medial dorsal nucleus (MDmc) was studied in the rhesus monkey (Macaca mulatta). The temporal pole region contains four architectonically defined cortical divisions. Medially, the allocortex of the temporal limb of the pyriform cortex is annexed to the temporal lobe neocortices at the limen insulae. Two transitional neocortices, the periallocortical and proisocortical divisions, are situated subjacent to the pyriform area. They make up the largest part of the temporal tip and separate the pyriform cortex from the architecturally more progressive isocortical divisions of the pole found laterally at the rostral ends of the superior and inferior temporal gyri. Neuroanatomical tracers were injected into each of the major divisions of the temporal pole cortex, and the injection site locations were characterized cytoarchitectonically as well as geographically. Injections of tritiated amino acids into pyriform allocortex or into the transitional neocortical fields revealed an efferent projection to the magnocellular medial dorsal nucleus. The terminal field was characterized by a mosaic type of organization and contained discrete zones of axonal termination in which bursts of coarse label surrounded neuronal perikarya and their proximal dendrites. A similar projection was also observed when horseradish peroxidase was injected into the transitional cortices. However, perikarya participating in the terminal clusters were not retrogradely labeled. Intracortical injections restricted to lateral polar isocortex did not result in either anterograde or retrograde transport of label to MDmc. These findings demonstrate a nonreciprocal, corticofugal pathway to MDmc that originates in the phylogenetically older districts of the temporal pole. The conduction of limbic sensory information directly from temporal neocortex to the medial thalamus may play a fundamental role in human and primate memory.     

Changes in visual responses in the feline dLGN: selective thalamic suppression induced by transcranial magnetic stimulation of V1

Transcranial magnetic stimulation (TMS) of the cortex can modify activity noninvasively and produce either excitatory or inhibitory effects, depending on stimulus parameters. Here we demonstrate controlled inhibitory effects on the large corticogeniculate feedback pathway from primary visual cortex to cells of the dorsal lateral geniculate nucleus (dLGN) that are focal and reversible-induced by either single pulses or trains of pulses of TMS. These effects selectively suppress the sustained component of responses to flashed spots or moving grating stimuli and are the result of loss of spikes fired in tonic mode, whereas the number of spikes fired in bursts remain the same. We conclude that acute inactivation of the corticogeniculate downflow selectively affects the tonic mode. We found no evidence to suggest that cortical inactivation increased burst frequency.     

Development,organization and plasticity of auditory circuits: Lessons from a cherished colleague

Ray Guillery was a neuroscientist known primarily for his ground‐breaking studies on the development of the visual pathways and subsequently on the nature of thalamocortical processing loops. The legacy of his work, however, extends well beyond the visual system. Thanks to Ray Guillery's pioneering anatomical studies, the ferret has become a widely used animal model for investigating the development and plasticity of sensory processing. This includes our own work on the auditory system, where experiments in ferrets have revealed the role of sensory experience during development in shaping the neural circuits responsible for sound localization, as well as the capacity of the mature brain to adapt to changes in inputs resulting from hearing loss. Our research has also built on Ray Guillery's ideas about the possible functions of the massive descending projections that link sensory areas of the cerebral cortex to the thalamus and other subcortical targets, by demonstrating a role for corticothalamic feedback in the perception of complex sounds and for corticollicular projection neurons in learning to accommodate altered auditory spatial cues. Finally, his insights into the organization and functions of transthalamic corticocortical connections have inspired a raft of research, including by our own laboratory, which has attempted to identify how information flows through the thalamus.     

Two populations of corticothalamic and interareal corticocortical cells in the subgranular layers of the mouse primary sensory cortices

The subgranular layers (layers 5 and 6) of primary sensory cortex provide corticofugal output to thalamus and they also project to the appropriate secondary sensory cortices. Here we injected two combinations of different color retrograde fluorescent markers in the thalamic and cortical targets of these layers from the three primary sensory cortices (somatosensory, auditory, and visual) in mice to examine the degree of overlap between corticothalamic and interareal corticocortical cells in the subgranular layers. We found that, for all three primary sensory cortices, double-labeled cells were extremely rare, indicating that corticothalamic and interareal corticocortical cells in the subgranular layers represent largely independent populations.     

Descending projections from the dysgranular zone of rat primary somatosensory cortex processing deep somatic input

In the mammalian somatic system, peripheral inputs from cutaneous and deep receptors ascend via different subcortical channels and terminate in largely separate regions of the primary somatosensory cortex (SI). How these inputs are processed in SI and then projected back to the subcortical relay centers is critical for understanding how SI may regulate somatic information processing in the subcortex. Although it is now relatively well understood how SI cutaneous areas project to the subcortical structures, little is known about the descending projections from SI areas processing deep somatic input. We examined this issue by using the rodent somatic system as a model. In rat SI, deep somatic input is processed mainly in the dysgranular zone (DSZ) enclosed by the cutaneous barrel subfields. By using biotinylated dextran amine (BDA) as anterograde tracer, we characterized the topography of corticostriatal and corticofugal projections arising in the DSZ. The DSZ projections terminate mainly in the lateral subregions of the striatum that are also known as the target of certain SI cutaneous areas. This suggests that SI processing of deep and cutaneous information may be integrated, to a certain degree, in this striatal region. By contrast, at both thalamic and prethalamic levels as far as the spinal cord, descending projections from DSZ terminate in areas largely distinguishable from those that receive input from SI cutaneous areas. These subcortical targets of DSZ include not only the sensory but also motor-related structures, suggesting that SI processing of deep input may engage in regulating somatic and motor information flow between the cortex and periphery.