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Mapping of stimulus features and meaning in gerbil auditory cortex with 2-deoxyglucose and c-Fos antibodies.

The basic functional organization of gerbil auditory cortex was previously mapped with unit recording of best frequency and with the fluoro-2-deoxyglucose mapping (FDG) technique. Among at least seven subfields in this cortex the primary auditory cortex (AI) and the anterior auditory field (AAF) showed prominent tonotopic organization with parallel dorsoventral iso-frequency contours (electrophysiology) in correspondence to FDG labelling of frequency band laminae. In an approach to mechanisms of learning aversive tone conditioning paradigms were found to reshape frequency receptive fields of single units in AI and also produced spatial shifts of tone representation in the tonotopic maps of AI and AAF. Both results suggest that spectral features as well as aspects of behavioural meaning of sounds may be represented even in primary auditory cortex. General meaningfulness in terms of occurrence of novel and salient stimuli may be reflected by expression of immediate early genes. Mapping with an antibody against the immediate early gene product c-Fos was performed in order to identify the spatial distribution of neurons in auditory cortex which change metabolism as a result of stimulation with auditory signals in a new environment. Very short e.g. less than 3 min repetitive stimulation with a tone led to frequency-specific columnar expression of c-Fos in AI and to spare non-tonotopic expression in other fields. Longer stimulation or longer aversive conditioning with the same tone led to spreading of expression, i.e. to accessory non-tonotopic labelling in AI and other fields, particularly pronounced in the output layers V and VI. It is assumed that this spreading relates to the formation of output schemes from auditory cortex in terms of implicit behavioural meaning of stimuli.

Animals↗

Plasticity in cat visual cortex restored by electrical stimulation of the locus coeruleus.

It has been proposed that the presence of noradrenaline (NA)-containing terminals and NA-related receptors within the visual cortex is necessary to maintain the high level of neuronal plasticity in the immature visual cortex of kittens. In the present study we wanted to show whether electrical stimulation of the locus coeruleus (LC), which contains the somata of these cortical NA fibers, can restore neuronal plasticity to the normally aplastic visual cortex of juvenile and adult cats. We consistently found a significant loss of binocular cells in the visual cortex of mature animals which had monocular vision for only 12 h dispersed over 6 days (2 h a day, otherwise kept in the dark) in combination with concurrent LC stimulation. This result was interpreted as indicating that endogenous NA released from NA terminals restored susceptibility to monocular vision in the mature visual cortex. We next examined how long the restored plasticity lasts in the same animals after the LC stimulation was ended. The animals revived from the first recording session were either returned to the same daily schedule of brief monocular exposure (light/dark = 2/22 h) as before, or subjected to the usual monocular lid suture and kept in a cat colony environment (light/dark = 16/8 h). The LC electrodes had been removed and no more electrical stimulation was delivered at this stage. In the animals subjected to reiteration of brief monocular exposure, the state of reduced binocularity gradually returned to normal over a period of 2-3 weeks after stopping LC stimulation. We calculated that the revived plasticity disappeared at an average rate of a 22% loss every 7 days. This result sharply contrasted with the result obtained in the animals subjected to usual monocular lid suture. In this test the state of reduced binocularity continued for at least the next 3 weeks, suggesting that the restored plasticity was sustained throughout a period of 3 weeks (longest term tested). The different results obtained in the two paradigms may be explained by the different strength of binocular imbalance in the two tests imposed on the visual cortex in which neuronal plasticity was restored partially.

Animals↗

Changes of drebrin expression in the visual cortex of the cat during development.

The expression of and developmental changes in drebrin were studied in cat visual cortex using immunohistochemistry and immunoblot analysis. Drebrin is a developmentally regulated brain protein which in the chicken has characteristic changes in expression related to developmental stage. A monoclonal antibody (MAb M2F6) raised against drebrin, was found to label the neuropil of the kitten visual cortex in the early postnatal period. At 1-3 weeks of age, the staining was prominent in layer IV of the visual cortex. The immunoreactivity, however, was found to be dramatically decreased around the end of the sensitive period for ocular dominance plasticity (approximately 3 months of age). In the adult visual cortex, almost no immunostaining was observed. These developmental changes revealed by an immunohistochemical method were confirmed using immunoblot analysis. Upon immunoblot analysis after SDS-PAGE of protein from the kitten visual cortex, MAb M2F6 was found to recognize two protein bands with molecular weights of 130 kDa (drebrin E) and 140 kDa (drebrin A). The developmental profile of the intensity of the two bands of the drebin closely parallels in time the postnatal changes in cortical susceptibility to visual deprivation. These results indicate that the expression of drebrin in kitten visual cortex is restricted to the early postnatal period and suggest that it may play an important role in the experience-dependent modification of cortical circuitry during the sensitive period.

Aging↗

NGFI-C expression is affected by physiological stimulation and seizures in the somatosensory cortex.

NGFI-C is an early response gene which encodes a Cys2/His2 zinc finger protein. NGFI-C has previously been demonstrated to be inducible in PC12 cells after NGF stimulation. This study sought to localize this gene in somatosensory cortex, and investigate its possible induction by physiological and seizure stimuli. To determine if NGFI-C message levels are affected by stimulation, RT-PCR was performed on mRNA extracts from somatosensory cortex. NGFI-C mRNA levels were increased to levels four-fold over baseline after a seizure. In a paradigm used as a model of experience-dependent plasticity, vibrissae stimulation also increased the level of NGFI-C expression in the contralateral barrel cortex to 180% of control levels. In situ analysis using digoxigenin-labelled cRNA probes demonstrated NGFI-C containing neurons throughout layers 2 through 6 in somatosensory cortex. A higher cell density was seen after stimulation. Qualitatively, staining was more intense in post-seizure and post-stimulus cortex than in control cortex. Analysis of related zinc finger expression in serial sections revealed that NGFI-C is expressed in a distinct but overlapping cell populations relative to NGFI-A, Krox 20, and Egr-3. These studies demonstrate the inducible nature of NGFI-C message in response to a physiological vibrissae stimulus, as well as to seizures. However, the levels and pattern of expression differ between these two stimuli.

Animals↗

Upregulation of intercellular adhesion molecule 1 (ICAM-1) on brain microvascular endothelial cells in rat ischemic cortex.

The expression of intercellular adhesion molecule 1 (ICAM-1) was studied in rat focal ischemic cortex. A significant increase in ICAM-1 mRNA expression in the ischemic cortex over levels in contralateral (nonischemic) site was observed by means of Northern blot analysis following either permanent or temporary occlusion with reperfusion of the middle cerebral artery (PMCAO or MCAO with reperfusion) in spontaneously hypertensive rats. In the ischemic cortex, levels of ICAM-1 mRNA increased significantly at 3 h (2.6-fold, n = 3, P < 0.05), peaked at 6 to 12 h (6.0-fold, P < 0.01) and remained elevated up to 5 days (2.5-fold, P < 0.05) after PMCAO. The profile of ICAM-1 mRNA expression in the ischemic cortex following MCAO with reperfusion was similar to that following PMCAO, except that ICAM-1 mRNA was significantly increased as early as 1 h (6.3-fold, n = 3, P < 0.05) and then gradually reached a peak at 12 h (12-fold, P < 0.01) after reperfusion. ICAM-1 mRNA expression in ischemic cortex following PMCAO was significantly greater in hypertensive rats than in two normotensive rat strains. Immunostaining using anti-ICAM-1 antibodies indicated that upregulated ICAM-1 expression was localized to endothelial cells of intraparenchymal blood vessels in the ischemic but not contralateral cortex. The data suggest that an upregulation of ICAM-1 mRNA and protein on brain capillary endothelium may play an important role in leukocyte migration into ischemic brain tissue.

Animals↗

Peptides and self-stimulation of the medial prefrontal cortex in the rat: effects of intracerebral microinjections of substance P and cholecystokinin.

The effects of intracerebral microinjections of substance P and cholecystokinin on self-stimulation of the medial prefrontal cortex of the rat were studied. Intracerebroventricular administration of substance P at doses of 2.5, 5, 10 and 20 micrograms produced a dose-related decrease in self-stimulation of the medial prefrontal cortex; spontaneous motor activity, measured as a control, was not affected. Unilateral microinjections into the medial prefrontal cortex of substance P at doses of 10 and 20 micrograms produced a decrease of self-stimulation of the ipsilateral side, but self-stimulation of the contralateral cortex, used as a control, was not affected. On the contrary, cholecystokinin in both intracerebroventricular administration at doses of 100, 200 and 400 ng, or intracortical microinjections into the medial prefrontal cortex at doses of 200, 400 and 800 ng, had no effect on self-stimulation of this cortical area. These results suggest that substance P, but not cholecystokinin, could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex in the rat.

Animals↗

Characteristics of endothelin receptors in the cerebral cortex and spinal cord of aged rats.

Characteristics of endothelin receptors were studied in male Fischer 344 rats at 4-, 15- and 24-months of age and [125I]ET-1 binding showed a single high affinity binding site in their cerebral cortex and spinal cord membranes. The density and affinity of ET binding sites were found to be similar in rats of various age groups. To determine the affinity of ET isotypes to ET-1 binding sites in cerebral cortex and spinal cord, competition studies were performed and K(i) values of ET-1, ET-2 and ET-3 for [125I] ET-1 binding sites were determined. It was found that ET-1 had 100 and ET-2 had 25-100 times lower K(i) values as compared to ET-3, indicating that ET receptors in cerebral cortex and spinal cord are of ETA type. In spinal cord, the K(i) values of ET-1 and ET-2 for ET receptor were found to be similar. However, in cerebral cortex the K(i) values of ET-1 were found to be at least 6 times lower than ET-2. It is inferred that there are two subtypes of ET(A) receptors, ET(A1) which have higher affinity for ET-1 in comparison to ET-2, as found in cerebral cortex and ET(A2) which have higher affinity for ET-2, as found in spinal cord. The K(i) and IC50 values of ET-1, ET-2, and ET-3 for [125I]ET-1 binding sites in cerebral cortex and spinal cord were found to be similar in 4-, 15- and 24-month-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Quantitative analysis of neuropathologic changes in the cerebral cortex of centenarians.

1. The quantitative distribution of neurofibrillary tangles and senile plaques was studied in the brains of 65 elderly patients aged from 96 to 104 years by immunohistochemistry. 2. According to the clinical and neuropathological diagnoses, three groups of cases were considered: 19 patients with Alzheimer's disease, 22 patients with mixed dementia (vascular and degenerative) and 24 patients with no or very mild cognitive impairment. 3. Moderate to high neurofibrillary tangle densities were always present in the hippocampus and entorhinal cortex. The inferior temporal cortex was very frequently affected in demented and non-demented cases whereas the superior frontal cortex was spared in the majority of cases independently of the clinical diagnosis. Quantitatively, Alzheimer's disease cases showed significantly higher NFT densities than cases with no clinical findings of dementia only in the CA1 field of the hippocampus. 4. The hippocampus and entorhinal cortex were often devoid of senile plaques in non-demented cases while the vast majority of Alzheimer's disease cases had few SP in these regions. The frontal and temporal cortex were more frequently involved than the limbic structures in both non-demented and Alzheimer's disease cases. The SP densities in layers II and III of the inferior temporal and superior frontal cortex were significantly higher in Alzheimer's disease than in non-demented cases. 5. These observations suggest that the dementing process in nonagenarians and centenarians may differ to that described in younger demented individuals in that neurofibrillary tangles involve principally the hippocampal formation with relative sparing of the neocortex. Furthermore, they indicate that both the neurofibrillary tangle densities in the CA1 field and senile plaque densities in the superficial layers of the neocortex must be considered for the neuropathological diagnosis of Alzheimer's disease in this age group.

Aged↗

Connections of the lateral cortex in the lizard Podarcis hispanica.

The connections of the lateral cortex of the lizard Podarcis hispanica have been traced using horseradish peroxidase transport techniques. After injections, restricted to the lateral cortex, labelled neurons can be observed bilaterally in the main olfactory bulbs and the diagonal band, contralaterally in the lateral cortex and ipsilaterally in the nucleus of the lateral olfactory tract, the ventral amygdaloid nucleus and also in the area triangularis. An efferent has also been shown on the ipsilateral medial cortex. This pattern of connections supports the hypothesis that the reptilian lateral cortex is comparable to the entorhinal and piriform cortex of mammals.

Animals↗

Age-dependence of the solubility fractions of acetylcholinesterase in the cerebral cortex and cerebellum of the rat.

Choline acetyltransferase (ChAT) activity in the cerebral cortex and the different solubility fractions of acetylcholinesterase (AChE) in the cerebral cortex and cerebellum were investigated in rats of different ages. ChAT activity was not decreased markedly in the cerebral cortex of 24- to 25-month-old rats compared to 3- to 4-month-old rats. The activity of detergent-soluble (DS) AChE in the cerebral cortex and cerebellum was lower in the older rats (24-25 months) rats than in younger (3-4 months) ones. The activity of DS-AChE in the cerebral cortex and cerebellum did not differ between 10- to 11-month-old and 24- to 25-month-old rats. The activity of low salt soluble (LSS) AChE in the cerebral cortex and cerebellum did not differ between older and younger rats.

Acetylcholinesterase↗

Cholecystokinin- and dopamine-containing mesencephalic neurons provide distinct projections to monkey prefrontal cortex.

Retrograde transport and immunohistochemical techniques were utilized to determine if cholecystokinin (CCK)-containing neurons of the primate ventral mesencephalon project to prefrontal cortex, and to examine what relation the CCK innervation of prefrontal cortex bears to the dopaminergic projection to this region. Following injections of Fast blue into monkey prefrontal cortex, retrogradely labeled, CCK-positive neurons were observed predominantly in rostromedial portions of the ventral mesencephalon; these CCK-containing projection neurons were not immunoreactive for tyrosine hydroxylase. Furthermore, dual-labeling studies in the prefrontal cortex revealed that CCK and tyrosine hydroxylase were present in separate populations of axons. These results demonstrate that the CCK innervation of monkey prefrontal cortex arises from both intrinsic and extrinsic sources; in contrast to the rat, the extrinsic CCK innervation of monkey prefrontal cortex is distinct from the dopaminergic mesocortical projection.

Animals↗

New observation on ubiquitinated neurons in the cerebral cortex of multiple system atrophy (MSA).

To investigate neuronal damage in the cerebral cortex in patients with multiple system atrophy (MSA), immunohistochemical stainings were carried out on the prefrontal cortex, the hippocampus, the precentral gyrus, the supplementary motor cortex and the occipital cortex in 6 cases of MSA and 6 controls, using antibodies against ubiquitin, tau protein and neurofilaments (BF10, RT97, 147). In MSA cases, a variable number of neuronal ubiquitinated inclusions were observed in the granule cell layer of the dentate gyrus (3/6) and the prefrontal cortex (3/6). An increased number of ubiquitinated dots-like structures were also observed in the parahippocampal gyrus of MSA cases (4/6) in comparison with controls. These results showed further evidence of neuronal damage in the cerebral cortex in MSA and strongly suggest a relationship between the cerebral cortical pathology and occasional manifestation of cognitive deficits in some MSA cases.

Atrophy↗

Estrogen receptors in the adrenal cortex of the possum (Trichosurus vulpecula).

1. Specific [3H]estradiol binding activity with characteristics of estrogen receptors was found in the cytosols and nuclear extracts of the adrenal cortex proper and special zone of the brushtail possum (Trichosurus vulpecula). 2. The specific estradiol receptor had a sedimentation coefficient on sucrose gradients of approximately 9S and a molecular weight on gel filtration of more than 200,000. The adrenal cortex cytosol binds [3H]estradiol with high affinity (Ka 5.5 X 10(9) M-1), and limited capacity (Bmax 62.7 fmol/mg cytosol prot). In competition experiments with different steroids the receptor showed a high affinity for four estrogens and a very low affinity to androgens, progesterone and cortisol. 3. There was no difference in the affinity and maximum binding capacity of the cytosols from cortex proper in male and female animals, but the binding capacity of the special zone of females was half that of cortex proper. Estradiol receptors were found in the kidney, liver, lung, testis and muscle but only in the adrenal and prostate was the binding capacity relatively high compared with the uterus. 4. The specific binding capacity of [3H]estradiol to cytosols of adrenal cortex at different stages of the estrus cycle and pregnancy was unrelated to that of the uterus. In the adrenal the receptor concentration was lowest at estrus, when uterine concentration was high, while in late pregnancy the binding of adrenal cortex and uterus cytosols was almost the same. 5. The possible physiological significance of the presence of a specific estrogen receptor in male and female possums is discussed.

Adrenal Cortex↗

Functional organization of thalamic projections to the motor cortex. An anatomical and electrophysiological study in the rat.

In rats, horseradish peroxidase crystals were injected in motor cortical foci functionally identified by means of the motor effects evoked by electrical stimulations. The location in the thalamus of the neurons linked to different motor cortical foci was studied. Thalamic neurons were retrogradely labeled in both "motor" (ventralis lateralis and ventralis medialis) and "non-motor" nuclei: centralis lateralis, lateralis posterior, mediodorsalis and posterior thalamic nuclear group, as well as the ventrobasal complex. The ventrobasal complex was labeled after horseradish peroxidase injections in hindlimb and trunk motor areas. The ascending projections toward the motor cortex from both "motor" and "non-motor" thalamic nuclei are organized more precisely and more elaborately than previously reported. The motor cortical afferents from the nucleus ventralis lateralis are organized in three planes, rostrocaudally, dorsoventrally and mediolaterally. An inverted relation exists in the rostrocaudal plane between the nucleus ventralis lateralis and the motor cortex: the caudal motor cortex region (hindlimb) receives fiber inputs from the rostral region of the nucleus ventralis lateralis, whereas the caudal zone of the nucleus ventralis lateralis projects to the rostral motor cortex region (forelimb and vibrissae). A dorsoventral organization has also been observed in the rostral region of the nucleus ventralis lateralis: the ventral aspect is the source of fibers directed to the distal hindlimb region, whereas fibers originating from the dorsal aspect are directed to the proximal hindlimb area. A mediolateral relationship exists between medial and lateral sides of the nucleus ventralis lateralis and, respectively, proximal and distal forelimb cortical areas. There is some overlap between the various nuclear regions thus delineated. Four functional zones were found in the lateral half of the nucleus ventralis medialis and were classified according to their projection to the motor cortex; these are involved in motor control of the proximal and distal forelimb, vibrissae and ocular movements. The projection is topographically organized according to both an inverted rostrocaudal and a direct dorsoventral-mediolateral arrangement. Caudally, dorsal and ventral nuclear parts project to rostromedial (vibrissae) and rostrolateral (distal forelimb) regions of the motor cortex, respectively. More rostral nuclear zones project to more caudal (proximal forelimb, eye) cortical regions. There is little overlap between these four nuclear subdivisions. The nucleus centralis lateralis projects to vibrissae and proximal, as well as distal, forelimb areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex.

We have used an antibody to the paired helical filament protein to immunohistochemically identify the regional distribution of subcortical nuclei containing neurofibrillary tangles in brains from Alzheimer's disease patients. Sections were examined from the cerebral cortex, diencephalon, midbrain and pons in seven Alzheimer's and three age-matched normal brains. The antibody sensitively stained the many tangles, and senile plaques, in the cerebral cortex of the Alzheimer's brains and the few tangles and senile plaques in the aged normal cortex. Ten subcortical nuclei contained many tangles in the Alzheimer's brains. The tangles were found not only within the locus coeruleus and dorsal raphe nucleus, which often have been shown to be involved in Alzheimer's neuropathology, but also within several other nuclei not previously related to this disease. For example, tangles were found in the nucleus paranigralis, peripeduncular nucleus, medial parabrachial nucleus and several midline thalamic nuclei. All of the nuclei which contained tangles have been shown, in neuroanatomical tracing studies, to project to the cerebral cortex. These data indicate that Alzheimer's disease is a disease of the cerebral cortex and the numerous subcortical nuclei which diffusely innervate it, and are consistent with the hypothesis that the cerebral cortex is the primary target of the disease and the interconnected subcortical nuclei are secondarily affected due to retrograde transport of a cortical pathogen or failure of normal transport of a trophic agent.

Afferent Pathways↗

Responses of amygdaloid central nucleus neurons to stimulation of the insular cortex in awake rabbits.

Recent evidence suggests that the amygdaloid central nucleus may contribute importantly to autonomic regulation during emotional states, possibly via both direct and indirect central nucleus efferent projections to autonomic regulatory nuclei in the lower brainstem. Additional findings suggest that the insular cortex may participate in autonomic regulatory processes, possibly by exerting an influence upon central nucleus neuronal activity via its direct projections to the central nucleus. The present experiment was conducted to determine the effects of insular cortex stimulation upon extracellularly recorded central nucleus neuronal activity in conscious, drug-free, rabbits. Satisfactory recordings were obtained from 146 central nucleus neurons. These were classified as belonging to one of six general categories on the basis of rates and patterns of ongoing discharge, responses to an auditory stimulus, and location within the nucleus. Determinations were then made as to whether each neuron could be activated antidromically from a ventrolateral mesencephalic region through which descending central nucleus projections to the lower brainstem course, and hence, whether the neuron might contribute to these projections. The activity of each neuron was then assessed during single-pulse stimulation of the region of the insular cortex demonstrated previously to project to the central nucleus. Such stimulation produced no response, an initial increase, or an initial decrease in the activity of 33%, 53% and 14% of the 146 neurons, respectively. The predominant response consisted of a single spike with a short but variable onset latency, suggesting orthodromic activation via one or a few synapses. Included among the neurons that responded to stimulation of the insular cortex in this manner were seven of 22 central nucleus neurons identified as projecting to the lower brainstem. Responses consisting of initially decreased activity most often occurred in neurons that discharged infrequently and were sensory-responsive. The results of this experiment thus provide more detailed information than was available previously regarding the pervasive influence of the insular cortex upon central nucleus neuronal activity, and provide further support for the notion that the insular cortex may participate in autonomic regulatory processes by way of its direct projections to the central nucleus.

Action Potentials↗

Functional consequences of modification of callosal connections by perinatal enucleation in rat visual cortex.

The effects of neonatal monocular enucleation (right eye) on the callosal connections in the rat visual cortex were studied by physiological and morphological methods. Evoked activity was recorded in the left hemisphere, i.e. contralaterally to the enucleated eye. After enucleation, trans-callosally evoked responses were recorded in a widened stripe of the lateral visual cortex. Compared with the controls, the responsive area was expanded laterally and medially, i.e. into the lateral part of the primary visual area and within the secondary visual cortex (lateral part). Within about 0.5 mm of the expansion, the responses did not differ from those recorded in areas with "normal" callosal connections. Morphological evidence is presented suggesting that this expansion of evoked responses with high amplitudes and short latencies corresponds to an extension of callosal connections with a high density of axon terminals in layers two and three. Further medially within the primary visual cortex, callosally evoked responses with low amplitudes and longer latencies were recorded. The main types of unit responses and characteristic interactions between visually and callosally evoked responses are shown and discussed. These results suggest that following neonatal enucleation (1) the callosal connections expand and form functional synapses in the lateral part of the visual cortex, (2) these connections can activate cortical neurons either directly or by mediation of associational connections between the lateral secondary and primary visual cortex areas and (3) callosal connections can interact with visually evoked potentials and unit responses.

Animals↗

Substance P-like immunoreactive neurons are depleted in Alzheimer's disease cerebral cortex.

We studied the morphology and distribution of substance P-like immunoreactive elements in normal and Alzheimer's disease brain with a monoclonal anti-substance P antibody. Bands of prominent terminal-like staining were found in the dentate gyrus of normal brain. Multipolar substance P-immunoreactive neurons were seen in dentate polymorphic layer and CA4 and prominent fiber staining was present in the CA fields of the hippocampus and adjacent allocortex. Reactive perikarya, concentrated in deep cortex and infracortical white matter, were found in all isocortical regions. Greatest density was in frontal and parietal association cortex; lowest in visual cortex. Fiber density was generally greatest in layers I and II. In Alzheimer's disease, staining intensity was reduced in the dentate gyrus. Hilar neurons were unaffected but other CA field neurons were distorted with pruned dendritic trees. Isocortical perikarya and fibers were significantly depleted and distorted in all regions. Globular deposits consisting of distorted neurites or dissolving perikarya were frequently seen. Double staining methods showed that the vast majority of isocortical, but not hippocampal, substance P-like immunoreactive neurons are nicotinamide adenine dinucleotide phosphate diaphorase-positive. Despite the modest quantitative depletion of substance P in Alzheimer's disease cortex as measured by radioimmunoassay compared to somatostatin, there is a significant depletion of substance P-like immunoreactive perikarya. This disparity may be due to persistence of afferent projections which make a major contribution to substance P concentrations in cerebral cortex or to the high substance P content of dystrophic fibers in Alzheimer's disease cortex.

Aged↗