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The effects of ablation of visual cortex in neonatal rabbits on the organization of retinothalamic and retinopretectal projections.

Primary visual cortex was ablated unilaterally in neonatal rabbits. Following a survival of 2-4 months, retrograde degeneration of the dorsal lateral geniculate nucleus (LGd) was assessed, and reorganization of retinofugal pathways was studied using methods of anretrograde transport of [3H]proline or of horseradish peroxidase. A complete lesion of primary visual cortex resulted in complete retrograde degeneration of the LGd with no sparing of any class of neurons. The terminations of retinofugal axons in the pretectum and thalamus were compared with those observed in normal animals. No major reorganization of ipsilateral retinofugal projections was observed in either the thalamus and pretectum ipsilateral to the ablated cortex, or in the thalamus and pretectum contralateral to the ablated cortex. However, contralateral retinofugal projections to the thalamus and to the pretectum ipsilateral to the ablated cortex were significantly different from normal. In the thalamus, the projections to the lateral posterior nucleus were expanded in area and increased in density. In the pretectum, the projections to the rostral pretectal areas were greatly increased in area, especially in the region of the olivary pretectal nucleus and posterior pretectal nucleus. However, the density of these projections was not increased relative to normal. Consideration of these results in relation to other published data on the anatomical consequences of neonatal visual cortex lesions, both in mammals which show behavioral sparing following neonatal visual cortex lesions and in mammals which, like the rabbit, show no behavioral sparing, suggests that: (1) behavioral sparing may correlate with patterns of survival or death of neurons in the thalamus and retina; and (2) reorganization of retinofugal pathways is not necessarily associated with behavioral sparing.

Animals↗

Temporal sequence of neurotransmitter expression by developing neurons of fetal monkey visual cortex.

The developing fetal monkey visual cortex was studied immunocytochemically from 110-155 days post-conception in order to localize cell populations immunoreactive (ir) for gamma-aminobutyric acid, Substance P, cholecystokinin-octapeptide, somatostatin, neuropeptide Y, and proenkephalin A peptide (BAM-18). The area 17/18 border and all cortical laminae identified in the adult visual cortex were discernible from the youngest age examined. All ir-cell populations studied were present at each fetal age. However, despite a relatively adult-like cytoarchitecture, all ir-cell populations studied displayed patterns of immunostaining which were unlike those described in adult visual cortex, and showed significant changes in laminar distribution, morphology, and numbers over the time course of gestation examined. Despite the differences in the patterns of immunostaining between the fetal and adult visual cortex, ir-cell populations intrinsic to the developing visual cortex exhibited adult-like combinations of co-localized transmitters and peptides. The developing monkey cortex also contains ir-cell populations, particularly BAM-18-ir cells, which have not been detected immunocytochemically in the adult monkey cortex. Differences between the fetal and the adult ir-cell populations might be accounted for by cell death, morphological transformation, secondary migration or changes in gene expression for neurotransmitters and neuropeptides.

Animals↗

An anterograde tracer study on the development of corticospinal projections from the medial prefrontal cortex in the rat.

The aim of the present study is to investigate, both qualitatively and quantitatively, the development of corticospinal (CS) projections from the medial prefrontal cortex of the rat. This study was carried out with the use of anterogradely transported wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) after iontophoretic injections in the medial prefrontal cortex. For comparison similar injections are made in the sensorimotor cortex. The CS axons of neurons situated in the medial prefrontal cortex have reached the first thoracic segment (T1) at postnatal day 3 (P3) and reach their most caudal extension in the spinal cord sixth thoracic segment (T6) at postnatal day 7 (P7) and then gradually disappear during the second postnatal week. Quantitative results revealed that after labelling of the medial prefrontal cortex no peaks in labelling density, neither at the cervical nor at the lumbar intumescence, were present. Furthermore, the CS axons of medial prefrontal neurons never showed any outgrowth into the spinal grey matter at any age studied. Concludingly, the extension and subsequent elimination of CS axons originating in the medial prefrontal cortex follow a similar time course as those from the occipital cortex (Dev. Brain Res., 36 (1987) 121-130).

Animals↗

Transient patterns of serotonergic innervation in the rat visual cortex: normal development and effects of neonatal enucleation.

The transient aggregation of serotonin (5-HT)-containing fibers in the early development of rat visual cortex was examined immunohistochemically. The aggregation of 5-HT immunoreactive (IR) fibers consisted of three stages which were classified according to the course of time and degree of space occupied. The primary aggregation appeared in the subplate and moved upward along the development of the cortex. The aggregation proceeded to the secondary stage in presumptive layer IV. The fibers extended in a column-like structure following the secondary aggregation and formed the tertiary aggregation. The upper edge of the tertiary aggregation formed a lattice-like pattern in layer I and its structure was recognized to be similar to the structure of a 'blob' which characterizes the primary visual cortex in monkey. This transient aggregation of 5-HT-IR fibers began in the subplate of the anterior visual cortex on postnatal day 2 (PND 2) and progressed towards the posterior. On PND 11, the secondary and tertiary aggregations were completed in the entire region. No further aggregation of 5-HT-IR fibers was observed on PND 15. The anterior-to-posterior axis in the aggregation process corresponds to the direction of differentiation in the layer structure of cortex. In order to investigate the relationship between the transient aggregation of 5-HT-IR fibers and the development of the visual pathway, the secondary and tertiary aggregation on PND 11 were observed after postnatal monocular or binocular enucleation. Enucleation of eye balls did not affect either the area occupied by the 5-HT-IR fibers in the secondary aggregation or the number of column structures in the tertiary aggregation. However, the contralateral and ipsilateral cortices of monocularly enucleated cases were irregularly shaped in the secondary aggregation. The distribution of 5-HT-IR fiber terminals in the binocular area (Oc1B) increased in density on the contralateral side in the monocular enucleation, while that of both sides in the binocular enucleation was of non-homogeneous density and were shaped irregularly. The above results suggest that the transient aggregation of 5-HT-IR fibers observed in the early stage of development of visual cortex is regulated primarily by the intrinsic factors, and that extrinsic factors, such as visual pathway input, affect the aggregation within the boundary of such intrinsic factors. That is, the visual pathway input and the input balance from both eyes affect the distribution density of 5-HT-IR fibers and the shape of the visual cortex, respectively.

Animals↗

Effects of lateral suprasylvian visual cortex lesions on visual localization, discrimination, and attention in cats.

Experiments were carried out to begin to define the behavioral functions of the lateral suprasylvian (LS) visual area of the cat's cortex. Behavioral tasks were chosen for analysis on the basis of previous suggestions in the literature concerning possible functions of LS cortex and its afferent pathways. These tasks included the ability of cats to orient the head and eyes to a stimulus presented in particular locations in the visual field, the ability to learn successive reversals of a two-choice visual pattern discrimination, and the ability to maintain or shift attention between relevant or irrelevant visual form and brightness cues. Eight cats were trained on each of these tasks. Four of the cats then received bilateral lesions of LS cortex, including the AMLS and PMLS regions, and the remaining 4 cats were used to assess normal retention. The LS cortex lesions had no significant effect upon performance of any of the behaviors tested. Thus, this region of cortex appears to play no essential role in simple brightness, form, and pattern discrimination performance, visual reversal learning, maintaining and shifting visual attention, or orienting the head and eyes to stimuli in the visual field. These results are discussed in relation to previous lesion studies involving large regions of the cat's extrastriate cortex and studies in other species. Possible functions of LS cortex, based upon recent electrophysiological studies, are suggested.

Animals↗

The primate premotor cortex fifty years after Fulton.

Fifty years ago, F.M.R. Walshe launched his famous diatribe against J.F. Fulton and his thesis that a premotor area with specialized functions exists within the agranular frontal cortex of primates. Now there is general agreement that the agranular frontal cortex contains at least 3 cortical fields: the primary motor cortex, the supplementary motor cortex, and the premotor cortex. This paper summarizes some of the evidence that the premotor cortex plays a role in the preparation for limb movements and presents speculation concerning the aspects of motor preparation in which the premotor cortex might be involved.

Animals↗

Inputs from motor and premotor cortex to the superior colliculus of the macaque monkey.

In retrograde studies of corticotectal projections in the monkey using horseradish peroxidase (HRP), projections of the frontal lobes were found to originate not only from the frontal eye fields and prefrontal association cortex but also from both motor and premotor cortex. Even small HRP injections into the superficial layers of the superior colliculus yielded labelled cells in the agranular cortex (area 6) of the anterior bank of the arcuate sulcus. After large collicular injections affecting all layers, labelled cells were found in both motor and premotor cortex. This projection appeared to be topographically organized. Injections into the anterolateral parts of the superior colliculus labelled cells that were distributed within the presumed finger-hand--arm-shoulder representation, whereas after more caudal injections labelled cells occurred more in the presumed arm-trunk representation. The supplementary motor cortex was not found to contain labelled cells. The corticotectal cells in the motor cortex differed from those in the premotor cortex in their size distribution; the former being small, the latter both small and large. The functional significance of the motor and premotor input into the superior colliculus for sensory, and particularly visual, guidance of movements is discussed in view of a collicular role in the extrapersonal space representation and of its possible participation in steering arm and hand movements.

Animals↗

Effect of phenylephrine and prazosin on the somatostatinergic system in the rat frontoparietal cortex.

Somatostatin (SS) and noradrenaline (NA) are distributed in the rat cerebral cortex, and seizure activity is one of the aspects of behavior affected by both neurotransmitters. Due to the possible interaction between both neurotransmitter systems, we studied whether phenylphrine, an alpha 1-adrenoceptor agonist, and prazosin, an alpha 1-adrenoceptor antagonist, can modulate SS-like immunoreactivity (SS-LI) levels, binding of [125I][Tyr11]SS to its specific receptors, the ability of SS to inhibit adenylate cyclase (AC) activity, and the guanine nucleotide binding regulatory protein G, and G., in the Sprague-Dawley rat frontoparietal cortex. An IP dose of 2 or 4 mg/kg of phenylephrine injected 7 h before decapitation decreased the number of SS receptors and increased the apparent affinity in frontoparietal cortex membranes. An IP dose of 20 or 25 mg/kg of prazosin administered 8 h before decapitation increased the number of SS receptors and decreased their apparent affinity. The administration of prazosin before the phenylephrine injection prevented the phenylephrine-induced changes in SS binding. The addition of phenylephrine and/or prazosin 10(-5) M to the incubation medium changed neither the number nor the affinity of the SS receptors in the frontoparietal cortex membranes. Phenylephrine or prazosin affected neither SS-LI content nor the basal or forskolin (FK)-stimulated AC activities in the frontoparietal cortex. In addition, SS caused an equal inhibition of AC activity in frontoparietal cortex membranes of phenylephrine-and prazosintreated rats compared with the respective control group. Finally, phenylephrine and prazosin did not vary the pertussis toxin (PTX)-catalyzed ADP ribosylation of Gi- and/or Go-proteins. These results suggest that the above-mentioned changes are related to the phenylephrine activation of alpha 1-adrenoceptors or to the blocking of these receptors by prazosin. In addition, these data provide further support for a functional interrelationship between the alpha 1-adrenergic and somatostatinergic systems in the rat frontoparietal cortex.

Adenosine Diphosphate Ribose↗

Tooth pulp-driven neurons in somatosensory cortex of primates: role in pain mechanisms including a review of the literature.

The tooth pulp of primates was stimulated electrically while searching for evoked unit potentials in the cerebral cortex. Control procedures were employed to assure that the electrical stimuli reached only tooth pulp fibers but no extrapulpal sensory fibers. In addition, an electrode was inserted in soft tissue surrounding the tooth for separate excitation of extrapulpal axons. A tooth pulp projection area was identified in the "face area" of primary somatosensory cortex. Two major neuron groups were encountered, one excited only by the extrapulpal soft tissue stimulus, the other by tooth pulp stimuli. Within the pulp-projection area, soft tissue-driven neurons were most numerous in superficial cortex of the postcentral gyrus, pulp-driven neurons dominated in deep cortex in the base of the central sulcus. The pulp-driven population divided into several functional subsets: those excited from one pulp only (conceivably capable of localizing pulpal stimuli), those excited from more than one pulp and those excited from both pulp and extrapulpal soft tissue. Within each of these 3 pulp-driven subsets, some units responded to single shock, others only to a train of shocks. Mean discharge latency was shortest for the population excited only from soft tissue, intermediate for pulp-driven units excited by single shock and longest for pulp-driven units excited only by trains of shocks. Both soft tissue and pulp stimuli evoked extensive inhibitory effects. In the Discussion, the possible role of pulp-driven neurons in pain is considered. The functional properties of some neurons are consistent with a role in stimulus localization but those of the remaining neurons suggest other roles in pain. An examination of the literature on cortex and pain suggests that normally somatosensory cortex is important for localizing painful stimuli and that it contributes to other pain mechanisms as well. After certain lesions, somatosensory cortex has the capacity for generating "central" pain just like other structures in the nociceptive pathway.

Animals↗

Biochemical mapping of cholecystokinin-, substance P-, [Met]enkephalin-, [Leu]enkephalin- and dynorphin A (1-8)-like immunoreactivities in the human cerebral cortex.

The distribution of immunoreactive cholecystokinin, substance P, [Met]enkephalin, [Leu]-enkephalin and dynorphin was determined in the cerebral cortex of the human brain post mortem. Peptide radioimmunoassays in three selected zones of the cortical gray mantle (frontal, temporal, occipital) revealed significant regional differences, prompting to the development of a new dissection procedure for the complete mapping of peptide-like materials throughout the entire cerebral cortex. For this purpose, frozen cerebral hemispheres were cut rostrocaudally in 21 verticofrontal serial sections, from which the cortical gray matter was divided into 4-5 distinct zones. The peptides could be measured in each of the 93 dissected pieces of tissue, but their distribution was uneven. The most abundant was cholecystokinin, particularly in the anterior part of the frontal lobe and in the temporal cortex, where its levels reached 0.5 ng/mg of tissue. The regional distribution of cholecystokinin resembled that of substance P with a decreasing gradient from the frontal to the occipital pole, but absolute levels of substance P were hardly one tenth of cholecystokinin levels. The mean concentrations of the three opioid peptides were even less than those of substance P, and their regional distributions were markedly different. [Met]Enkephalin was concentrated in the occipital cortex, and [Leu]enkephalin in the temporal cortex. Dynorphin was the least abundant, even in the temporal cortex where the highest levels were found. The widespread and heterogeneous distribution of these peptides strongly suggests that each of them exerts specific functions in the human cerebral cortex.

Aged↗

Effects of motor cortex and single muscle stimulation on neurons of the lateral vestibular nucleus in the rat.

The neuronal responses to stimulation of motor cortical sites and of forelimb single muscles were studied in the lateral vestibular nucleus of anaesthetized rats. Of the 228 neurons tested for response to stimulation of contralateral motor cortex, 63% responded to cortical sites controlling extensor muscles and 30% to those controlling flexors. The corresponding figures for responders to ipsilateral stimulation were 34 and 21%. Vestibulospinal units responded to cortical sites controlling extensor and flexor muscles whereas the remaining lateral vestibular nucleus neurons, very reactive to cortical sites controlling extensor muscles, responded little to contralateral and not at all to ipsilateral cortical sites controlling flexor muscles. The effects evoked by contralateral cortical sites controlling extensors varied, those induced by cortical sites controlling flexors were inhibitory in 77% of cases. The responses to ipsilateral motor cortex stimulation differed not so much by cortical sites controlling extensor or flexor muscles as by whether the neuron was in the dorsal or ventral zone of the lateral vestibular nucleus: mixed in the former, all inhibitory in the latter. Of the lateral vestibular nucleus units tested for response to stimulation of ipsilateral or contralateral forelimb distal muscles, only 11% responded. All the vestibulospinal units responsive to muscle stimulation lay in the dorsal zone of the nucleus. The remainder, dorsal or ventral, were not responsive to contralateral muscles. Single lateral vestibular nucleus cells influenced both by ipsilateral muscle and by contralateral motor cortex made up 24% of the pool, vestibulospinal and non-vestibulospinal. They fell into three groups: responsive to one or both structures but responding more strongly to combined stimulation; responsive to each of the two structures but showing a response to combined stimulation not significantly different from that evoked by the cortex alone; responsive only to combined stimulation. The lateral vestibular nucleus units included in these three groups accounted for 29% of those tested for response to extensor muscles and cortical sites controlling extensors and 15% of those tested for response to flexor muscles and cortical sites controlling flexors. Twenty-five per cent of the vestibulospinal neurons responded both to contralateral muscles and to ipsilateral motor cortex stimulation but none of the non-vestibulospinal neurons responded to both. All the responders to both were in the dorsal zone of the lateral vestibular nucleus and responded to extensor stimuli, always in the same way. These results indicate that motor cortex output exerts a major influence on lateral vestibular nucleus discharges, while the muscle afferents have a modulatory influence on the lateral vestibular nucleus responses to cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390.

A widespread distribution of dopamine D1 receptors in the neocortex is well recognized. However, the presence of dopamine D2 receptors in this structure has only recently been established [Martres et al. (1985) Eur. J. Pharmac. 118, 211-219; Lidow et al. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 6412-6416]. In the present paper, a highly specific antagonist, [3H]raclopride, was used for autoradiographic determination of the distribution of D2 receptors in 12 cytoarchitectonic areas of the frontal, parietal, and occipital lobes of the rhesus monkey. A low density of D2-specific [3H]raclopride binding (1.5-4.0 fmol/mg tissue) was detected in all layers of all cortical areas studied. Throughout the entire cortex, the highest density of binding was consistently found in layer V. This is a unique distribution not observed so far for any other neurotransmitter receptor subtype in monkey cerebral cortex, including D1 receptor. In addition, a comparison was made of the distribution of [3H]raclopride and [3H]spiperone, which has been commonly used in previous attempts to label cortical D2 receptors. We found marked differences in the distribution of these two radioligands. In the prefrontal cortex, the pattern of [3H]spiperone binding in the presence of ketanserin resembled the combined distribution of 5-HT1C serotoninergic and alpha 2-adrenergic sites as well as D2 receptors. Thus, [3H]raclopride provides a better estimation of the D2 receptor distribution than does [3H]spiperone. The distribution of D2-specific binding of [3H]raclopride was also compared with the D1-specific binding of [3H]SCH23390 in the presence of mianserin to block labeling to 5-HT2 and 5-HT1C sites. The density of D1-specific [3H]SCH23390 binding was 10-20 times higher than that of D2-specific [3H]raclopride binding throughout the cortex. The densities of both [3H]raclopride and [3H]SCH23390 binding sites display a rostral-caudal gradient with the highest concentrations in prefrontal and the lowest concentrations in the occipital cortex. However, the binding sites of these two ligands had different laminar distributions in all areas examined. In contrast to preferential [3H]raclopride binding in layer V, a bilaminar pattern of [3H]SCH23390 labeling was observed in most cytoarchitectonic areas, with the highest concentrations in supragranular layers I, II and IIIa and infragranular layers V and VI. Whereas [3H]raclopride binding was similar in all cytoarchitectonic areas, [3H]SCH23390 exhibited some region-specific variations in the primary visual and motor cortex. The different regional and laminar distributions of D1 and D2 dopaminergic receptors indicates that they may subserve different aspects of dopamine function in the cerebral cortex.

Animals↗

The organization of serotonergic projections to cerebral cortex in primates: regional distribution of axon terminals.

Serotonergic axons are widely distributed in the primate forebrain and represent the most abundant ascending projection from the reticular formation. Immunocytochemical methods have been utilized to examine the density, laminar distribution and morphology of serotonergic axons in both primary projection (motor, somatosensory) and association areas (dorsolateral prefrontal, area 5) as well as in the hippocampus and in cingulate cortex of rhesus and cynomolgus macaques. Serotonergic axons are present in all areas of cortex examined, and all cortical layers receive serotonergic afferents. However, the intracortical distribution of serotonergic axon terminals is not uniform; rather, different regions of cortex exhibit dissimilarities in both the density and laminar distribution of serotonergic axons. Thus, there are local patterns of serotonin innervation that are characteristic of each cortical area. Highly diverse patterns of serotonin innervation are found in heterotypical areas of cortex; more subtle variations are present among homotypical areas. Two morphologic types of serotonergic axon terminals, fine and beaded, are present in all cortical areas, and they typically exhibit different laminar distributions: in most areas of neocortex, beaded axons predominate in layer I while fine axons predominate in layers II-VI. However, exceptions to this pattern were observed in primary visual cortex and in the hippocampal formation. The distinctive local patterns of serotonin innervation observed in this study indicate that raphe-cortical projections are likely to have differential influences on particular cytoarchitectonic areas of cerebral cortex in the primate. Moreover, the discrete laminar distribution of serotonin axons suggests that serotonergic projections selectively innervate particular neuronal elements in cerebral cortex. The present findings suggest that the two classes of serotonergic axons, fine and beaded, which have different patterns of termination, affect different sets of cortical neurons. In addition, these two serotonergic projections may be associated with different sets of serotonergic receptors and thus produce selective effects on cortical function.

Afferent Pathways↗

Transplants of embryonic cortical tissue placed in the previously damaged frontal cortex of adult rats: local cerebral glucose utilization following execution of forelimb movements.

Transplantation of fetal cortical tissue into the motor cortex of adult rats was used as an experimental model to examine the functional integration of homotopic fetal neocortical grafts into the motor pathways of adult host brain. We have employed the [14C]2-deoxy-D-glucose method to analyse the metabolic activity of the transplant and host sensorimotor cortex: (i) in animals solicited to perform specific lever-pressing movements with the limb contralateral to the transplant (experimental group); and (ii) in non-solicited animals or in animals using the limb ipsilateral to the transplant (control group). Grafts in the control group displayed homogeneous uptake of 2-deoxy-D-glucose throughout the rostrocaudal extent of the transplant. The local cerebral glucose utilization levels were low as compared to those of the surrounding cortex but were at least two-times higher than in the corpus callosum. Increase in 2-deoxy-D-glucose uptake by the transplant cells was found only in the experimental group. In this group, 2-deoxy-D-glucose uptake was higher in the caudal (AP: +3.0 to +1.7 mm, relative to Bregma) than in the rostral sectors of the transplants suggesting the existence of a topographic organization within the transplant. In addition, except in the rostral part, glucose utilization was higher in the transplant of the experimental group than in the sensorimotor areas of the non-activated cortex in the control group. Moreover, glucose utilization of the transplant cells was systematically higher in the experimental than in the control group. The transplants appear to display a certain level of metabolic integration with the host sensorimotor cortex since, in the experimental group, there was no significant differences in local cerebral glucose utilization values in the caudal sector of the transplant and in the surrounding sensorimotor cortical areas of the host. The 2-deoxy-D-glucose uptake was even higher in the caudal sector of the transplant than in some of the subfields of the contralateral sensorimotor cortex. The present findings indicate for the first time that motor activation of the contralateral forelimb produces an increase in metabolic activity in distinct transplant sectors, the topographic distribution of which matches the normal topographic organization of the forelimb somatomotor map. This suggests that transplants of embryonic frontal neocortex placed in the frontal cortex of adult hosts become functionally integrated with the host motor system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Afferent connections of the caudolateral orbitofrontal cortex taste area of the primate.

A cortical taste region has recently been identified in the caudolateral orbitofrontal cortex of the macaque. The afferents to this region were investigated by means of retrograde tracing, using six injections of wheatgerm-conjugated horseradish peroxidase. The area of taste cortex was first identified physiologically in all the monkeys used in this anatomical study. The four injections into the middle and posterior part of this region resulted in large numbers of labelled cell bodies in the insular-opercular primary taste cortex. Following the two more anterior injections, label was found predominantly in the caudal part of the cardolateral orbitofrontal cortex itself. None of the injections resulted in labelled cells in the gustatory thalamic nucleus ventralis posterior medialis, pars parvocellularis, although all injections resulted in label of the mediodorsal nucleus of the thalamus. Afferents were also seen from more anterior parts of the orbitofrontal taste cortex, which may represent backprojections from subsequent taste areas. These results suggest that the caudolateral orbitofrontal cortex contains a higher-order taste cortex.

Amygdala↗

Developmental expression of alpha 7 neuronal nicotinic receptor messenger RNA in rat sensory cortex and thalamus.

The distribution of alpha 7 messenger RNA expression was characterized in developing rat cortex and thalamus. Northern blot analysis of neonatal and adult cortex revealed a single messenger RNA transcript of 5.7 kb. Using in situ hybridization with both full length and short 35S-labeled alpha 7 riboprobes, a distinct transient expression of messenger RNA within sensory cortex and thalamus, during early postnatal development, was observed. alpha 7 transcripts were expressed in low levels as early as embryonic day 13 in the ventricular zone of the neocortex, and as early as embryonic day 15 in the thalamic neuroepithelium. A marked increase in messenger RNA levels was observed during the late prenatal period in both sensory and non-sensory regions of the cortex and thalamus. Moderate to high levels of messenger RNA were maintained into the first postnatal week, followed by a decline into adulthood. alpha 7 messenger RNA expression was significantly higher in the anterodorsal, lateral dorsal, ventral posterior medial and ventral posterior lateral thalamic nuclei of postnatal day 7 pups than in adult brains. Expression of messenger RNA within dorsal lateral geniculate, ventral lateral geniculate and medial geniculate did not show a significant reduction with age. Within the developing cortex, messenger RNA expression delineated the primary somatosensory, auditory and visual cortices in a unique laminar pattern that was consistently and significantly higher than in the adult in superficial layer VI. Higher levels of expression were also observed in retrosplenial cortex at postnatal day 7 than in the adult. Tangential sections through postnatal day 7 cortex revealed low levels of alpha 7 messenger RNA expression delineating the primary sensory areas in layer IV, corresponding to acetylcholinesterase-labeled thalamocortical afferents. However, these sensory areas exhibited higher levels of alpha 7 messenger RNA expression and were more clearly defined in layer VI, but not by acetylcholinesterase staining. The distribution of alpha 7 messenger RNA within the developing thalamocortical system parallels the distribution of alpha-bungarotoxin binding sites and suggests that the receptor is localized on both thalamic cells and their cortical target neurons. This transient and distinct pattern of distribution of the alpha 7 neuronal nicotinic receptor, which coincides with the major phase of thalamocortical development, suggests that it may play a functional role in the development of cortical circuitry.

Acetylcholinesterase↗

Anatomical evidence for convergence of olfactory, gustatory, and visceral afferent pathways in mouse cerebral cortex.

Flavor perception requires the neural integration of olfactory, gustatory and, possibly, visceral afferent information. Presently, it is not known where, or how this integration takes place in the brain. Neuroanatomical data presented here suggest that pathways subserving these sensory modalities converge in mouse insular cortex after surprisingly few synaptic relays. Orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to label main olfactory bulb (MOB) efferents. A projection into layer I of insular cortex was present in every case. Bulb transections were made to provoke anterograde degeneration and EM analysis confirmed that the olfactory projection to insular cortex was a terminal pathway. WGA-HRP injections in the MOB-recipient zone of insular cortex resulted in ortho and retrograde labeling of ascending and descending gustatory-visceral afferent pathways. It is concluded that in the mouse, there is a remarkably direct convergence of olfactory and gustatory-visceral sensory pathways in insular cortex. Together with the descending connections from insular cortex to the amygdala and to brainstem autonomic structures, it is possible that the cortical integration of olfactory and gustatory-visceral information could modulate mechanisms involved in food selection and autonomic reactions relating to the chemical senses. Basic mechanisms subserving flavor perception might be usefully modelled in mouse insular cortex.

Afferent Pathways↗

Effect of haloperidol on immunoreactive neuropeptide Y in rat cerebral cortex and basal ganglia.

To clarify the dopaminergic regulation of neuropeptide Y (NPY) neurons, the effect of haloperidol on NPY in basal ganglia and the cerebral cortex of the rat brain was investigated by sensitive radioimmunoassay and immunocytochemistry using antiserum against rat NPY. After repeated intraperitoneal injections of haloperidol (5 mg/kg) for 6 days, the content of immunoreactive NPY was significantly decreased in the caudate-putamen, but significantly increased in the lateral prefrontal cortex. After treatment for 21 days, the content of immunoreactive NPY in the caudate-putamen remained significantly low, but the extent of change in the lateral prefrontal cortex diminished. In the medial prefrontal cortex, piriform cortex, parietal cortex and nucleus accumbens, no significant changes were found after treatment for either 6 or 21 days. These findings were compatible with those obtained by immunocytochemistry using the same antiserum: an increase of immunoreactive fibers and terminals in the lateral prefrontal cortex and their decrease in the caudate-putamen. However, in the nucleus accumbens the density of immunoreactive fibers and terminals was decreased in the rostral portion, but not in the caudal portion after haloperidol treatment for 6 and 21 days. These findings suggest that dopaminergic afferents region-specifically regulate dopamine-sensitive NPY neurons in the rat brain.

Animals↗