Areas Of Neocortex Research Articles

Selective increase in lipid peroxidation in the inferior temporal cortex in Alzheimer's disease

The concentration of a product of lipid peroxidation (malondialdehyde) was determined in six areas of neocortex of 8 subjects with Alzheimer's disease and 8 control subjects. Malondialdehyde concentration was significantly increased by incubation with iron and ascorbate in all samples. Both basal and iron/ascorbate-stimulated malondialdehyde concentration were higher in the inferior temporal cortex of Alzheimer subjects than corresponding controls; other regions were unaffected. Basal concentrations of malondialdehyde correlated with age in both the inferior parietal lobule and the sensory/motor cortex.

Effects of baroreceptor stimulation on sensorimotor control of the hand.

Finger movements are presumed to be controlled by somatosensory and motor areas of neocortex via the corticospinal tract. Since baroreceptor activation appears to reduce central nervous system activity, an effect on sensorimotor control during precise manual manipulations is expected. To test this hypothesis, motor responses to slow and fast perturbations during grasping of a small object (precision grip) were examined. Baroreceptor activation was manipulated with the phase-related external suction (PRES) technique, which allows the application of baroreceptor stimulation and control conditions in a well-controlled and indiscernible way. Motor reactions following slow perturbations were influenced in the expected way in good-performance subjects. The time to stop slow perturbations was longer and the electromyographic (EMG) activity of the small thumb muscles was lower during baroreceptor stimulation than in the control condition. These effects did not appear in the fast-perturbation task. Fast perturbations were followed by EMG activity onset after about 50 msec, which indicates that a prominent part of the EMG activity must be attributed to a more automatic motor response. EMG activity following slow perturbations began after about 90 msec, and it may be assumed that these motor reactions are primarily under voluntary control. The fact that we found effects of baroreceptor stimulation in slow but not in fast perturbations could have been caused by at least partially different pathways utilized for automatic versus voluntary motor responses, which seem to be differentially vulnerable to baroreceptor activation. An electrocortical sign that precedes voluntary movements is the Bereitschaftspotential, or readiness potential. Since this potential is a slow brain potential, and baroreceptor activation is known to reduce slow brain potentials, it is plausible that baroreceptor activation primarily affects motor responses following slow but not fast perturbations.

Neuronal processes that underlie expression of kindled epileptiform events in the piriform cortex in vivo

Recent studies with kindling and convulsant drug models of epilepsy suggest that the piriform (primary olfactory) cortex may be particularly susceptible to generation of epileptiform activity. The present study has examined the generation of interictal epileptiform events in the piriform cortex of kindled rats in vivo, taking advantage of special features of this system that facilitate physiological analysis. The investigation included analysis of extracellular and intracellular potentials, and membrane currents computed by current source density (CSD) analysis. In pyramidal cells, epileptiform events consisted of an initial EPSP that occurred in all-or-none fashion and a long-lasting IPSP with Cl(-)- and K(+)-mediated components. Onset of the IPSP was sufficiently fast that firing evoked by the EPSP was consistently limited to single action potentials. CSD analysis revealed the presence of two distinctly different excitatory epileptiform currents: an initial inward current of unknown origin that is widely distributed over depth, and a second much larger inward current at the depths of proximal apical and basal dendrites of pyramidal cells. It was concluded that this second component is mediated by the associational projections of pyramidal cells excited by the first component. Since these heavy associational projections also extend to neighboring areas including the amygdala, entorhinal cortex, and insular and orbitofrontal areas of neocortex, this second component could be widely propagated within the basal forebrain. An important finding was that the EPSP generated by this associational pathway was completely blocked in cell bodies of pyramidal cells in piriform cortex by the IPSP during most events. This IPSP may therefore play a critical role in limiting seizure activity by preventing reverberating positive feedback in the pyramidal cell population. It can be speculated that compromise of this IPSP, as by repetitive activation by the shock trains used for kindling, leads to prolonged epileptic activity in the piriform cortex and the many limbic structures to which it projects.

Receptor Changes in the Neocortex of Post-Mortem Tissue in Parkinson's Disease and Alzheimer's Disease

Benzodiazepine and muscarinic receptors in the neocortex were studied using homogenate binding techniques and in vitro autoradiography (ARG). Tritiated flunitrazepam was used to bind to the benzodiazepine portion of the γ-aminobutyric acid receptor. Tritiated quinuclidnyl benzilate was used to locate the muscarinic receptor. Tissue samples from four areas of neocortex from cases of Parkinson''s disease, Alzheimer''s disease and age-matched controls were used for homogenate binding experiments to estimate binding parameters. Tissue for ARG provided more detailed anatomical localization of the relevant receptors. Homogenate binding studies showed that the receptor density, as measured by maximum binding capacity for tritiated flunitrazepam, was significantly reduced in the frontal cortex in Parkinson''s disease. In Alzheimer''s disease there was reduced binding of flunitrazepam in all portions of the neocortex studied, reaching statistical significance in the frontal and temporal cortex. The dissociation constant, indicating receptor affinity for flunitrazepam, was unaltered in all areas studied. ARG demonstrated that the distribution of benzodiazepine receptor loss within different cortical layers was distinct in Parkinson''s and Alzheimer''s disease. In control brains, the greatest density of benzodiazepine receptors was seen in regions corresponding to layers II and III. This peak was greatly reduced in the frontal cortex of Parkinson''s disease, while in Alzheimer''s disease the loss was more uniform. There was no significant alteration in the binding parameters of the muscarinic cholinergic receptors in either of these disease states.

Alterations in hippocampal function following repeated exposure to the amphetamine derivative methylenedioxymethamphetamine (“Ecstasy”)

The effect of the psychomotor stimulant, 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), upon integrated cerebral function was measured in rats using the quantitative [14C]deoxyglucose autoradiographic technique. Animals were injected with MDMA (20 mg/kg sc) twice daily for 4 days. Fourteen days after the final administration, [3H]-paroxetine binding to 5HT uptake sites was reduced by 89% in membranes prepared from tissue samples of frontal cortex. In the same rats [3H]-paroxetine binding autoradiography revealed heterogeneity in the regional distribution of 5-HT uptake site depletion within neocortex (0-92%) and hippocampus (30-95%). Despite these profound reductions in 5-HT uptake sites no significant alterations were found in glucose utilisation in any area of neocortex examined. However, significant increases in glucose use were found in subregions of the hippocampus, most notably within the pyramidal cell layer of CA2 and CA3 (25-35%). This study provides direct evidence that the loss of 5-HT innervation caused by exposure to MDMA results in lasting functional changes in hippocampus.

Horizontal long-term potentiation of responses in rat somatosensory cortex

The search for mechanisms in neocortex that change synaptic efficacy and produce associative learning through activity-dependent processes has focused on the role of glutamate receptors of the N-methyl- d-aspartate (NMDA) type. NMDA receptor activation is necessary for the induction of long-term potentiation (LTP) in hippocampus 12 and in neocortex 2. The effect of NMDA receptor activation is modulated in several ways, including Mg 2+ block of the NMDA-dependent channel which prevents Ca 2+ entry until neurons become partially depolarized 25,32. We report that when NMDA receptor activation is facilitated by lowering the extracellular [Mg 2+] in the bathing medium, a low-frequency train presented in layer VI induces potentiated responses throughout a wide horizontal extent of layer II/III in neocortical slices. The response amplitudes potentiated by 34–200% over baseline values depending on the intensity of the repetitive conditioning stimulus and the distance of the recording site from the stimulus. At the same time that pre-existing evoked responses were potentiated, horizontal spread of activity in layer II/III was facilitated resulting in responses appearing at sites more than 1 mm from the stimulus. This enhanced transmission of responses persisted for >2 h, and its induction was prevented by s spread of activity can be increased by altering the conditions of the stimulus presentation. We conclude that the mechanisms supporting LTP could determine the area of neocortex that is activated by a sensory input.

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.

Characterization of two pathological Tau protein variants in Alzheimer brain cortices

Tau proteins were detected in brain tissue homogenates from 10 patients with Alzheimer's disease versus 10 age-matched controls using the immunoblot technique and 2 polyclonal antibodies: anti-paired helical filaments (PHF) and anti-human native Tau proteins. In control brains, both antisera detected identically the normal set of Tau proteins, with molecular weight (MW) ranging from 45 to 62 kDa. Moreover, in association areas of neocortex from Alzheimer brains, the antisera detected 2 additional Tau variants of 64 and 69 kDa. Tau 64 and 69 were not found in regions of Alzheimer brains where the Alzheimer pathology was absent (caudate nucleus or cerebellum for example). The heavy MW of Tau 64 and 69 is due to their phosphorylation state as shown by the decrease of their MW after alkaline phosphatase treatment. Therefore, Tau 64 and Tau 69 are specific markers of the Alzheimer's disease neuronal degenerating process and their characterization demonstrates that an abnormal phosphorylation of Tau really occurs during the disease. Tau 64 and 69 were isolated with normal Tau proteins while the PHF were insoluble. Therefore, Tau proteins are likely to be abnormally phosphorylated prior to their incorporation in the PHF structure. Consequently, they might appear before the lesions and might be instrumental for the search of biochemical deregulations that precede the neurofibrillary degeneration.

Periodicity and directionality in the propagation of epileptiform discharges across neocortex.

1. The horizontal propagation of epileptiform discharges has been studied in slices of neocortex treated with high concentrations of bicuculline methiodide, an antagonist of the inhibitory transmitter gamma-aminobutyric acid (GABA). The cortical areas examined were: primary somatosensory (SmI) and motor (MI), and primary (area 17) and secondary (area 18) visual areas of rats, and area 17 of cats. In all of these areas an electrical stimulus evoked single, all-or-none paroxysmal field potentials (PFPs) that propagated across the entire width of the slice without decrement. 2. The velocity of PFP propagation was approximately 0.06-0.09 m/s when averaged over cortical distances of several millimeters. PFP propagation occurred equally well in both directions across a slice. 3. Measurement of PFP propagation at higher spatial resolution (100-180 micron intervals) revealed that velocity was not homogeneous within rat SmI, rat area 18 and cat area 17, but instead varied manyfold as horizontal position changed. In these areas of cortex, propagation patterns were spatially periodic; power spectra reveal that the dominant spatial frequencies were centered about 1 mm-1, with negligible contributions above 2 mm-1. Occasionally PFP propagation was discontinuous, skipping over a small region of cortex and arriving distally before propagating into the more proximal region. 4. In those cortices with periodic propagation patterns, PFP velocity was also strongly direction-dependent. Propagation patterns measured in opposite directions across the same strip of cortex displayed similar periodicities, but in many slices they were negatively correlated, i.e., the propagation pattern in one direction was antiphasic compared to that in the other direction. 5. In contrast, propagation velocity across the center of area 17 of the rat was relatively constant and not directional. Near the boundaries of areas 17 and 18, however, PFP velocity changed abruptly and became periodic within area 18. Similarly, velocity within rat MI was more constant and less directional than in the adjacent SmI. 6. The patterns of PFP propagation velocity are often spatially periodic, directionally asymmetric, and depend upon cortical area. We suggest that the periodic patterns reflect systematic variations in the length or density of horizontal excitatory connections. Alternatively, or concurrently, periodicities could arise from the patchy distributions of intrinsic connections that have been observed anatomically in many areas of neocortex.

Organization of feedback and feedforward projections of the barrel cortex: a PHA-L study in the mouse.

In order to analyze the organization of the efferent projections of single barrel columns (BC, i.e. a barrel in layer IV of parietal cortex plus the cortical tissue above and below it), we made small iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin in the barrel cortex of 20 adult mice. On the basis of reconstructions of the sites of terminal labelling, the brain regions receiving projections from the barrel cortex could be identified and classified in five groups. Each group is characterized by the topography of the distribution of efferents arising from a single BC. The projections to the trigeminal sensory complex are point to point: i.e. one BC projects only to the site of termination of the primary sensory neurons innervating the corresponding whisker follicle. In the ventrobasal thalamic nucleus BC projections are not restricted to the corresponding barreloid; instead they contract parts of barreloids belonging to one arc. In the reticular and posterior thalamic nuclei the projections from a row of BC's converge to a collective termination site, whereas in the superior colliculus the projections from an arc of BC's converge to a common termination site. There is a complete overlap of BC projections in restricted zones within SII, motor cortex, perirhinal cortex, contralateral barrelfield, caudoputamen and pons. The organization of the efferents from the barrel cortex demonstrates a contrast between feedback and feedforward projections from this important area of neocortex.

Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity

The psychotropic amphetamine derivatives 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) have been used for recreational and therapeutic purposes in man. In rats, these drugs cause large reductions in brain levels of serotonin (5-HT). This study employs immunocytochemistry to characterize the neurotoxic effects of these compounds upon monoaminergic neurons in the rat brain. Two weeks after systemic administration of MDA or MDMA (20 mg/kg, s.c., twice daily for 4 d), there is profound loss of serotonergic (5-HT) axons throughout the forebrain; catecholamine axons are completely spared. Regional differences in drug toxicity are exemplified by partial sparing of 5-HT axons in hippocampus, lateral hypothalamus, basal forebrain, and in some areas of neocortex. The terminals of 5-HT axons are selectively ablated, while axons of passage and raphe cell bodies are spared. Thickened preterminal fibers exhibit increased staining due to damming-up of neurotransmitter and other axonal constituents. Fine 5-HT axon terminals are extremely vulnerable to these drugs, whereas terminal-like axons with large varicosities survive, raising the possibility that some 5-HT axons may be resistant to the neurotoxic effects. At short survivals, visualization of greatly swollen, fragmented 5-HT axons provides anatomic evidence for degeneration of 5-HT projections. The results establish that MDA and MDMA produce structural damage to 5-HT axon terminals followed by lasting denervation of the forebrain. Both drugs have similar effects, but MDA produces a greater reduction of 5-HT axons than does MDMA at the same dosage. The selective degeneration of 5-HT axons indicates that these drugs may serve as experimental tools to analyze the organization and function of 5-HT projections. Caution should be exercised until further studies determine whether these compounds may be hazardous in man.

The early development of subcortical projections to presumptive somatic sensory-motor areas of neocortex in the North American opossum

We have studied the early development of subcortical projections to presumptive somatic sensory-motor areas of neocortex in the North American opossum Didelphis virginiana. The opossum is born in a very immature state, 12-13 days after conception, and climbs into an external pouch where it is available for experimental manipulation. Using the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, we have obtained evidence that axons from the dorsal raphe and superior central nuclei, the substantia nigra, the locus coeruleus and the parabrachial nuclei reach presumptive somatic sensory-motor areas of neocortex by at least postnatal day (PND) 10. Axons showing serotonin-like immunoreactivity, presumably from the dorsal raphe and/or superior central nuclei, and axons containing tyrosine hydroxylase immunoreactivity, presumably from the substantia nigra and/or locus coeruleus, are present in the same areas at birth or shortly thereafter. Thalamic axons do not grow into comparable areas of neocortex until after PND 10. Such axons reach the subplate region of ventrolateral neocortex first and then proceed dorsomedially; by estimated PD (EPND) 21, they are present in presumptive layers I, V and VI, but they do not innervate an identified layer IV until EPND 48. The developmental sequences suggested by our study are compared with those reported for other species and are discussed in light of their importance in the formation of major sensory and motor circuits.

Development of brainstem and cerebellar projections to the diencephalon with notes on thalamocortical projections: studies in the North American opossum.

The North American opossum is born in a very immature state, 12 days after conception, and climbs into an external pouch where it remains attached to a nipple for an extended period of time. We have taken advantage of the opossum's embryology to study the development of brainstem and cerebellar projections to the diencephalon as well as the timing of diencephalic projections to somatosensory motor areas of neocortex. The techniques employed included immunocytochemistry for serotonin, the retrograde and orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, and the selective impregnation of degenerating axons. Our results suggest that serotoninergic axons, presumably from the dorsal raphe and superior central nuclei, are present in the diencephalon at birth. Axons from the bulbar reticular formation, the vestibular complex, the trigeminal sensory nuclei, and the dorsal column nuclei reach at least mesencephalic (and probably diencephalic) levels by postnatal day (PND) 3, whereas those from the cerebellar nuclei may not grow into comparable levels until PND 5. The dorsal column and cerebellar nuclei innervate the ventral nuclei of the thalamus by estimated postnatal day (EPND) 17 and all of the diencephalic nuclei supplied in the adult animal by EPND 26. Diencephalic axons enter ventrolateral (face) areas of presumptive somatosensory motor cortex by PND 12, but do not reach dorsomedial (limb) regions until EPND 21. At both ages, diencephalic axons are limited to the cortical subplate and marginal zone; they do not innervate an identifiable internal granular layer until considerably later. Our results suggest that axons from the brainstem and cerebellum grow into the diencephalon early in development, but that they do not influence the cerebral cortex until relatively late. When the results of the present study are compared with those reported previously on the development of ascending spinal (Martin et al., '83) and corticofugal (Martin et al., '80; Cabana and Martin, '85b,c) projections, it appears that specific components of major somatosensory and motor circuits develop according to different timetables.

Development of projections from somatic motor‐sensory areas of neocortex to the diencephalon and brainstem in the North American opossum

The development of projections from somatic motor-sensory areas of neocortex to the diencephalon and brainstem was studied by using the orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in a series of pouch-young opossums. The opossum was chosen for study because it is born in a very immature state, 12 days after conception, and has a protracted postnatal development. Cortical axons form a cerebral peduncle by at least postnatal day (PD) 10, a medullary pyramid by estimated PD (EPD) 17, a pyramidal decussation by EPD 26, and reach the first cervical segment of the spinal cord by EPD 29. Cortical axons innervate diencephalic nuclei and perhaps the substantia nigra by EPD 17, but do not grow into more caudal brainstem nuclei until EPD 26. The first brainstem areas innervated by cortical axons are the mesencephalic and rostral pontine tegmentum and parts of the pontine gray adjacent to the pyramidal tract (EPD 29). By EPD 31, cortical axons project to additional areas of the pontine gray, the gigantocellular reticular formation, the medial accessory olive, and the cuneate nucleus. Cortical innervation of the red nucleus and superior colliculus begins at EPD 31 but is not well developed until EPD 35. Cortical axons do not innervate the parvicellular reticular formation or the sensory trigeminal nuclei until EPD 35. Evidence for transient cerebrocerebellar axons was also found.

The development of commissural connections of somatic motor-sensory areas of neocortex in the North American opossum.

The North American opossum does not have a corpus callosum; neocortical commissural axons are contained entirely within the anterior commissure. We have used axonal transport techniques to study the origin and distribution of commissural axons from somatic motor-sensory cortex in developing and adult opossums. Neocortical axons grow into the anterior commissure by postnatal day (PND) 12, the contralateral external capsule by approximately PND 19, the area deep to the contralateral homotypic cortex by approximately PND 26 and the cortex proper by approximately PND 35. Commissural neurons were first demonstrated at about PND 26, when they form a fairly continuous band in the cortical subplate (presumptive layers V-VI). By at least PND 37, commissural neurons are also present in layers II and III, where they form a continuous band, and in layer IV, where they are sparse. In older pouch young and adult opossums the bands of commissural neurons, especially in layers V-VI, are interrupted, and commissural neurons are rare in layer IV. In general, commissural axons in both pouch-young and adult opossums innervate areas containing commissural neurons as well as layer I. In the acallosal opossum as well as in the callosal rat, the development of commissural connections from somatic motor-sensory cortex is characterized by pauses during the growth of axons into the opposite cortex, by a general inside-out-gradient, and by a transition from continuous bands to patchy, radial columns of commissural neurons and axons. This suggests that similar mechanisms govern the formation of commissural connections in the two species.

Organization of raphe-cortical projections in rat: A quantitative retrograde study

Retrograde transport of a fluorescent dye was employed to study the projections from raphe nuclei to neocortex in the rat. The spatial distributions of labeled raphe cells were analyzed quantitatively to determine whether the nuclei are topographically organized with respect to different cortical targets. The dorsal raphe nucleus (DRN), exclusive of the lateral wing regions, has a predominantly (3:1) ipsilateral projection with decreasing numbers of cells projecting to frontal, parietal, and occipital cortex. Overlapping cell groups within the DRN project differentially to these three conical areas: DRN cells innervating frontal cortex extend more rostrally and laterally than those to either parietal or occipital cortex. The median raphe and B9 projections are bilaterally symmetric, with equal cell numbers projecting to frontal, parietal, and occipital cortex. The rostro-caudal distributions of cells that project to disparate cortical areas differ in B9 but not in MR. The percentage of cortically projecting cells that are serotonergic is 80% for the DRN, 60% in the MR and 33% in the B9 cell group. The dorsal raphe nucleus and the B9 cell group are organized heterogeneously, and overlapping sets of neurons project differentially upon particular areas of neocortex. In contrast, the median raphe nucleus projects uniformly upon the neocortex and does not exhibit topographic organization. The three rostral raphe nuclei (DR, MR and B9) are each organized according to different rules with regard to their efferent projections to cortex. The differential organization of the raphe nuclei suggests that groups of cells within these three raphe nuclei are likely to innervate different combinations of cortical targets and thus to have different functional effects.

Functional anatomy of the inferior colliculus and the auditory cortex: current source density analyses of click-evoked potentials.

In the auditory midbrain (inferior colliculus) and cortex (superior temporal gyrus) of awake squirrel monkeys profiles of click-evoked field potentials were recorded. The recording tracks were reconstructed anatomically. From the field potentials the one-dimensional current source density (CSD) distributions were calculated. By comparing the CSD profiles with the anatomical features of the reconstructed recording paths, the components of the CSDs could be attributed to certain anatomical sites. Thus a physiological method for the functional identification of recording sites was obtained. It permits the identification of depth locations of specific laminae in cortex. In the inferior colliculus it permits distinction between central and peripheral regions and between three depth segments. The CSDs in the central nucleus of the inferior colliculus lend functional support to the anatomical division into three distinct parts and, in addition, provide the temporal aspects of the main groups of synaptic activities. The CSDs in the auditory cortex permit determination of five different groups of excitatory synaptic activations. The spatio-temporal distributions of these components are very similar to those obtained in other neocortical areas and thus corroborate the hypothesis that afferent activity is relayed very similarly in all sensory areas of neocortex.

Nongeniculate afferents to striate cortex in macaques.

Horseradish peroxidase (HRP) was injected in relatively massive amounts to cover most, or portions, of opercular striate cortex in four macaques. Absence of transcallosal or circumventricular labelling, plus discrete and consistent retrograde labelling in other areas in the four cases, assured the validity and specificity of the observations. Numerous labelled cells in regions directly bordering striate cortex, however, were excluded from the analysis because of the possibility of uptake consequent to physical diffusion. With this exception, all labelled cells were counted at roughly 2-mm intervals for one case with extensive unilateral injection of HRP. Even excluding the closely circumstriate population, the totals indicate that more than 30% of the afferent input to striate cortex arises from nongeniculate sources. Four areas of neocortex together make up about one-fourth of the total afferents: superior temporal sulcus 17.1%; inferior occipital area, 6.1%; intraparietal sulcus, 0.4%; and parahippocampal gyrus, 0.3%. Other areas projecting to striate cortex include claustrum, pulvinar, nucleus paracentralis, raphé system, locus coeruleus, and the nucleus basalis of Meynert. Cells of the latter were particularly striking with their very heavy uptake of HRP, and, even in cases of minimal effective injection, were scattered throughout an extensive area from the posterior edge of the globus pallidus passing rostrally beyond the chiasm and into the nucleus of the diagonal band. On the basis of their distribution and known cholinergic affinity, it is argued that this group also includes the cells labelled in and around lateral hypothalamus and cerebral peduncle, and that as a whole the group constitutes a cholinergic counterpart of the diffusely projecting monoaminergic systems. It seems possible that the basalis projection at first follows a fornical-subcallosal pathway to reach striate cortex via callosoperforant fibers.

Local cerebral glucose utilization in hypothermic and hyperthermic rats.

Local rates of glucose utilization in 38 regions of the CNS were measured in conscious, lightly restrained rats during normothermia (rectal temperature, 37.4 +/- 0.1 degrees C, hypothermia (31.8 +/- 0.1 degrees C), and hyperthermia (40.2 +/- 0.3 degrees C). In 34 of the 38 regions examined (the four exceptions being primary auditory nuclei in the lower brainstem), a significant relationship could be demonstrated between the rate of glucose utilization and body temperature. The magnitude of temperature-related alterations in glucose use displayed considerable regional heterogeneity. In hypothermic rats the reductions in glucose use were proportionately most marked (reduced 35-50% from normothermic) in thalamic nuclei, extrapyramidal and motor areas, septohippocampal formation, and some areas of neocortex and white matter; they were least pronounced in anterior hypothalamus (reduced by 13%), habenula (by 16%), and amygdala (by 22%). In hyperthermic rats, significantly increased glucose utilization was observed in only 16 of the 38 areas examined (e.g., hypothalamus, hippocampus, extrapyramidal system, and raphe nucleus), whereas in a number of major areas (such as the neocortex and thalamus) glucose use was minimally altered with hyperthermia. The regional heterogeneity in the alterations in glucose utilization suggests that caution must be exercised in the interpretation of autoradiographic 2-deoxyglucose investigations in which body temperature disturbances occur.

An analysis of some thalamic projections to parietofrontal neocortex in the marsupial native cat, Dasyurus viverrinus (Dasyuridae).

Thalamocortical projections to parietofrontal neocortex in the marsupial native cat, Dasyurus viverrinus, were examined using the retrograde transport of horseradish peroxidase. The results show that the organisation in Dasyurus is similar to that reported in another Australian marsupial, the brush-tailed possum, Trichosurus vulpecula, and is different to that found in the primitive American form, Didelphis virginiana. In Daysurus, as in Trichosurus, the areas of neocortex receiving projections from the trigeminothalamic system do not appreciably coincide with those areas receiving input from the cerebellothalamic system. In Didelphis there appears to be complete overlap of these areas of motor and somaesthetic neocortex. These results suggest that the motor--somaesthetic organisation in Australian marsupials is divergent from the presumed stem pattern seen in the American forms. If the Australian marsupials, as is now believed, were isolated from the stem Polyprotodonta in the upper Cretaceous, it would appear that the Australian marsupials may have begun to develop certain aspects of their characteristic CNS configuration very early, as the oldest known marsupial fossils are not much older than this.