Showing papers in "The Journal of Neuroscience in 1984"
TL;DR: The results show that damage to the parietal lobe produces a deficit in the disengage operation when the target is contralateral to the lesion, and suggest one mechanism of the effects of parietal lesions reported in clinical neurology.
Abstract: The cognitive act of shifting attention from one place in the visual field to another can be accomplished covertly without muscular changes. The act can be viewed in terms of three internal mental operations: disengagement of attention from its current focus, moving attention to the target, and engagement of the target. Our results show that damage to the parietal lobe produces a deficit in the disengage operation when the target is contralateral to the lesion. Effects may also be found on engagement with the target. The effects of brain injury on disengagement of attention seem to be unique to the parietal lobe and do not appear to occur with our frontal, midbrain, and temporal control series. These results confirm the close connection between parietal lobes and selective attention suggested by single cell recording. They indicate more specifically the role that parietal function has on attention and suggest one mechanism of the effects of parietal lesions reported in clinical neurology.
2,086 citations
TL;DR: The results suggest that a system involved in the processing of color information, especially color-spatial interactions, runs parallel to and separate from the orientation-specific system.
Abstract: Staining for the mitochondrial enzyme cytochrome oxidase reveals an array of dense regions (blobs) in the primate primary visual cortex. They are most obvious in the upper layers, 2 and 3, but can also be seen in layers 4B, 5, and 6, in register with the blobs in layers 2 and 3. We compared cells inside and outside blobs in macaque and squirrel monkeys, looking at their physiological responses and anatomical connections. Cells within blobs did not show orientation selectivity, whereas cells between blobs were highly orientation selective. Receptive fields of blob cells had circular symmetry and were of three main types, Broad-Band Center-Surround, Red-Green Double-Opponent, and Yellow-Blue Double-Opponent. Double-Opponent cells responded poorly or not at all to white light in any form, or to diffuse light at any wavelength. In contrast to blob cells, none of the cells recorded in layer 4C beta were Double-Opponent: like the majority of cells in the parvocellular geniculate layers, they were either Broad-Band or Color-Opponent Center-Surround, e.g., red-on-center green-off-surround. To our surprise cells in layer 4C alpha were orientation selective. In tangential penetrations throughout layers 2 and 3, optium orientation, when plotted against electrode position, formed long, regular, usually linear sequences, which were interrupted but not perturbed by the blobs. Staining area 18 for cytochrome oxidase reveals a series of alternating wide and narrow dense stripes, separated by paler interstripes. After small injections of horseradish peroxidase into area 18, we saw a precise set of connections from the blobs in area 17 to thin stripes in area 18, and from the interblob regions in area 17 to interstripes in area 18. Specific reciprocal connections also ran from thin stripes to blobs and from interstripes to interblobs. We have not yet determined the area 17 connections to thick stripes in area 18. In addition, within area 18 there are stripe-to-stripe and interstripe-to-interstripe intrinsic connections. These results suggest that a system involved in the processing of color information, especially color-spatial interactions, runs parallel to and separate from the orientation-specific system. Color, encoded in three coordinates by the major blob cell types, red-green, yellow-blue, and black-white, can be transformed into the three coordinates, red, green, and blue, of the Retinex algorithm of Land.
1,546 citations
TL;DR: The first systematic survey of the responses of IT neurons to both simple stimuli and highly complex stimuli indicates that there may be specialized mechanisms for the analysis of faces in IT cortex.
Abstract: Previous studies have reported that some neurons in the inferior temporal (IT) cortex respond selectively to highly specific complex objects. In the present study, we conducted the first systematic survey of the responses of IT neurons to both simple stimuli, such as edges and bars, and highly complex stimuli, such as models of flowers, snakes, hands, and faces. If a neuron responded to any of these stimuli, we attempted to isolate the critical stimulus features underlying the response. We found that many of the responsive neurons responded well to virtually every stimulus tested. The remaining, stimulus-selective cells were often selective along the dimensions of shape, color, or texture of a stimulus, and this selectivity was maintained throughout a large receptive field. Although most IT neurons do not appear to be “detectors” for complex objects, we did find a separate population of cells that responded selectively to faces. The responses of these cells were dependent on the configuration of specific face features, and their selectivity was maintained over changes in stimulus size and position. A particularly high incidence of such cells was found deep in the superior temporal sulcus. These results indicate that there may be specialized mechanisms for the analysis of faces in IT cortex.
1,387 citations
TL;DR: The data suggest that the increased calcium influx accompanying an increased firing rate triggers burst firing, possibly by inactivating a potassium conductance.
Abstract: In addition to firing in a single spiking mode, dopamine (DA) cells have been observed to fire in a bursting pattern with consecutive spikes in a burst displaying progressively decreasing amplitude and increasing duration. In vivo intracellular recording demonstrated the bursts to typically ride on a depolarizing wave (5 to 15 mV amplitude). Although the burst-firing frequency of DA cells showed little correlation with the base line firing rate, increases in firing rate were usually associated with an increase in burst firing. Increases in burst firing could also be elicited by intracellular calcium injection and could be prevented by intracellular injection of EGTA, suggesting a calcium involvement in bursting. Blockade of potassium conductances with extracellular iontophoresis of barium or intracellular injection of tetraethylammonium bromide could also trigger an increased degree of burst firing in DA cells. These data suggest that the increased calcium influx accompanying an increased firing rate triggers burst firing, possibly by inactivating a potassium conductance. A switch from a single spiking mode to a burst-firing mode may be important in modulating striatal DA release, as shown for burst firing in other preparations.
1,343 citations
TL;DR: A mathematical model is presented which predicts both the major qualitative features and, within experimental error, the quantitative details of a class of perturbed and unperturbed large-amplitude, voluntary movements performed at intermediate speed by primates.
Abstract: This paper presents a mathematical model which predicts both the major qualitative features and, within experimental error, the quantitative details of a class of perturbed and unperturbed large-amplitude, voluntary movements performed at intermediate speed by primates. A feature of the mathematical model is that a concise description of the behavioral organization of the movement has been formulated which is separate and distinct from the description of the dynamics of movement execution. Based on observations of voluntary movements in primates, the organization has been described as though the goal were to make the smoothest movement possible under the circumstances, i.e., to minimize the accelerative transients. This has been formalized by using dynamic optimization theory to determine the movement which minimizes the rate of change of acceleration (jerk) of the limb. Based on observations of muscle mechanics, the concept of a “virtual position” determined by the active states of the muscles is rigorously defined as one of the mechanical consequences of the neural commands to the muscles. This provides insight into the mechanics of perturbed and unperturbed movements and is a useful aid in the separation of the descriptions of movement organization and movement execution.
1,228 citations
TL;DR: The selective distribution of CGRP throughout sensory, motor, and autonomic areas of the spinal cord suggests many putative roles for this novel peptide.
Abstract: Calcitonin gene-related peptide (CGRP) immunoreactivity was found throughout the entire spinal cord of man, marmoset, horse, pig, cat, guinea pig, mouse, rat, and frog. CGRP-immunoreactive fibers were most concentrated in the dorsal horn. In the ventral horn of some species large immunoreactive cells, tentatively characterized as motoneurons, were present. Pretreatment of rats with colchicine enhanced staining of these large cells but did not reveal CGRP-immunoreactive cell bodies in the dorsal horn. In the dorsal root ganglia, CGRP immunoreactivity was observed in most of the small and some of the intermediate sized cells. Substance P immunoreactivity, where present, was co-localized with CGRP to a proportion of the small cells. In the cat the ratio of substance P-immunoreactive to CGRP-immunoreactive ganglion cells was 1:2.7 (p less than 0.001). The concentration of CGRP-immunoreactive material in tissue extracts was determined by radioimmunoassay. In the dorsal horn of the rat spinal cord the levels of peptide were found to range from 225.7 +/- 30.0 pmol/gm of wet weight in the cervical region to 340.6 +/- 74.6 pmol/gm in the sacral spinal cord. In the rat ventral spinal cord, levels of 15.7 +/- 2.7 to 35.1 +/- 10.6 pmol/gm were found. The concentration in dorsal root ganglia of the lumbar region was 225.4 +/- 46.9 pmol/gm. Gel permeation chromatography of this extractable CGRP-like immunoreactivity revealed three distinct immunoreactive peaks, one eluting at the position of synthetic CGRP and the others, of smaller size, eluting later. In cats and rats, rhizotomy induced a marked loss of CGRP-immunoreactive fibers from the dorsal horn of the spinal cord. In the cat, unilateral lumbosacral dorsal rhizotomy resulted in a significant (p less than 0.05) reduction of extractable CGRP from the ipsilateral lumbar dorsal horn (5.6 +/- 1.2 pmol/gm of wet weight) compared to the contralateral side (105.0 +/- 36.0 pmol/gm of wet weight). We conclude that the major origin of CGRP in the dorsal spinal cord is extrinsic, from afferent fibers which are probably derived from cells in the dorsal root ganglia. The selective distribution of CGRP throughout sensory, motor, and autonomic areas of the spinal cord suggests many putative roles for this novel peptide.
1,006 citations
TL;DR: Results provide convincing evidence that the synaptic release of excitatory transmitter mediates the death of anoxic neurons, and suggests new strategies that may be effective in preventing the devastating insults produced by cerebral hypoxia and ischemia in man.
Abstract: The pathophysiology of hypoxic neuronal death, which is difficult to study in vivo, was further defined in vitro by placing dispersed cultures of rat hippocampal neurons into an anoxic atmosphere Previous experiments had demonstrated that the addition of high concentrations of magnesium, which blocks transmitter release, protected anoxic neurons These more recent experiments have shown that gamma-D-glutamylglycine (DGG), a postsynaptic blocker of excitatory amino acids, was highly effective in preventing anoxic neuronal death DGG also completely protected the cultured neurons from the toxicity of exogenous glutamate (GLU) and aspartate (ASP) In parallel physiology experiments, DGG blocked the depolarization produced by GLU and ASP, and dramatically reduced EPSPs in synaptically coupled pairs of neurons These results provide convincing evidence that the synaptic release of excitatory transmitter, most likely GLU or ASP, mediates the death of anoxic neurons This result has far-reaching implications regarding the interpretation of the existing literature on cerebral hypoxia Furthermore, it suggests new strategies that may be effective in preventing the devastating insults produced by cerebral hypoxia and ischemia in man
889 citations
TL;DR: In vivo intracellular injection of the calcium chelator EGTA will cause DA cells to fire in a regular, pacemaker pattern, with the amplitude of the afterhyperpolarization being proportional to the number of spikes in a train.
Abstract: Dopamine (DA) neurons have been recorded in vivo in four states of activity: hyperpolarized, nonfiring; single spike firing; burst firing; and depolarization inactivation Nonfiring DA neurons can be made to fire by iontophoretic application of the excitatory substances glutamate and cholecystokinin, or by depolarizing current injection Spontaneously active DA cells typically fire in a slow (3 to 8 Hz) irregular pattern In vivo intracellular recordings revealed that this pattern is sustained by the alternation of two currents: a spontaneously occurring slow depolarization (13 +/- 3 mV amplitude, 78 +/- 40 msec duration) which brings the membrane potential of the DA cell to spike threshold (-42 mV), and an afterhyperpolarization mediated by a calcium-activated potassium conductance (IK(Ca)) The slow depolarization is a pacemaker-like conductance, with a rate of rise proportional to the membrane potential The regular pacemaker pattern of the spontaneously occurring slow depolarization is interrupted by the IK(Ca) which appears to be triggered by calcium entry during the action potential Thus, intracellular injection of the calcium chelator EGTA will cause DA cells to fire in a regular, pacemaker pattern The IK(Ca) is observed after single spikes and trains of spikes with the amplitude of the afterhyperpolarization being proportional to the number of spikes in a train Both the afterhyperpolarization and the firing accommodation observed during depolarizing current injection can be blocked by intracellular injection of the calcium chelator EGTA
874 citations
TL;DR: Neurons within the RVL, most probably C1 adrenaline- synthesizing neurons, exert an excitatory influence on sympathetic vasomotor fibers, the adrenal medulla, and the posterior pituitary, as well as under tonic inhibitory control, in part via GABAergic mechanisms.
Abstract: We have studied the responses to electrical and chemical stimulation of the ventrolateral medulla in the chloralose-anesthetized, paralyzed, artificially ventilated rat Locations of most active pressor responses were compared to regions containing neurons labeled immunocytochemically for phenylethanolamine N-methyltransferase (PNMT), the enzyme catalyzing the synthesis of adrenaline Elevations of arterial pressure (+816 +/- 25 mm Hg) and cardioacceleration (+73 +/- 136 bpm) were elicited with low current (5 times threshold of 95 +/- 11 microA) electrical stimulation in a region of rostral ventrolateral medullary reticular formation we have termed the nucleus reticularis rostroventrolateralis (RVL) Electrical stimulation of the RVL increased plasma catecholamines (168-fold for adrenaline, 53-fold for noradrenaline, and 19-fold for dopamine) and vasopressin (17-fold before spinal transection, 47-fold after) The location of the most active pressor region in the ventrolateral medulla corresponded closely with the location of C1 adrenaline-synthesizing (PNMT-containing) neurons In addition, the location of the most active pressor region in the dorsomedial medulla corresponded with the location of a bundle of PNMT-containing axons Unilateral injections into the RVL of the excitatory amino acid monosodium L-glutamate (50 pmol to 10 nmol), but not saline, caused transient dose-dependent and topographically specific elevations (maximum +716 +/- 49 mm Hg) of arterial blood pressure and tachycardia Injections of the rigid structural analogue of glutamate, kainic acid, caused large, prolonged (at least 15 min) pressor responses and tachycardia Unilateral injections of the inhibitory amino acid gamma-aminobutyric acid (GABA) into the RVL caused transient dose-dependent hypotension (maximum -408 +/- 66 mm Hg) and bradycardia, whereas the specific GABA antagonist bicuculline caused prolonged (10 to 20 min) elevations (+642 +/- 68 mm Hg) of arterial pressure and tachycardia By contrast, injections of the glycine antagonist strychnine had no significant effect Bilateral injections of the neurotoxin, tetrodotoxin, dropped arterial pressure to low levels (517 +/- 47) not changed by subsequent spinal cord transection at the first cervical segment (525 +/- 62) We propose the following (1) Neurons within the RVL, most probably C1 adrenaline-synthesizing neurons, exert an excitatory influence on sympathetic vasomotor fibers, the adrenal medulla, and the posterior pituitary (2) These neurons are tonically active and under tonic inhibitory control, in part via GABAergic mechanisms--perhaps via the nucleus of the solitary tract (NTS)(ABSTRACT TRUNCATED AT 400 WORDS)
838 citations
TL;DR: Karger et al. as mentioned in this paper used retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase to examine the origin of thalamic input to the two premotor areas with the densest projections to the motor cortex.
Abstract: We have used retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase to examine the origin of thalamic input to the two premotor areas with the densest projections to the motor cortex: the arcuate premotor area (APA) and the supplementary motor area (SMA) Retrograde transport demonstrated that the two premotor areas and the motor cortex each receive thalamic input from separate, cytoarchitectonically well defined subdivisions of the ventrolateral thalamus According to the nomenclature of Olszewski (Olszewski, J (1952) The Thalamus of the Macaca mulatta An Atlas for Use with the Stereotaxic Instrument, S Karger, AG, Basel), input to the APA originates largely from area X, input to the SMA originates largely from the pars oralis subdivision of nucleus ventralis lateralis (VLo), and that to the motor cortex originates largely from the pars oralis subdivision of nucleus ventralis posterior lateralis (VPLo) These observations, when combined with prior studies on the termination of various subcortical efferents in the thalamus, lead to the following scheme of connections: (1) rostral portions of the deep cerebellar nuclei project to the motor cortex via VPLo; (2) caudal portions of the deep cerebellar nuclei project to the APA via area X; and (3) the globus pallidus projects to the SMA via VLo Thus, each thalamocortical pathway is associated with a distinct subcortical input
768 citations
TL;DR: The hypothesis that a desired joint position is determined by the ratio of the tensions of agonist and antagonist muscles is tested and it is concluded that the processes underlying trajectory formation must be more complex than a simple switch between one equilibrium position and another.
Abstract: One hypothesis for the generation of spatially oriented arm movements by the central nervous system is that a desired joint position is determined by the ratio of the tensions of agonist and antagonist muscles. According to this hypothesis, the transition between equilibrium states should be solely a function of the contraction time of the motor units and the mechanical properties of the arm. We tested this hypothesis in intact and deafferented rhesus monkeys by holding the forearm and measuring the accelerative transient after release of the forearm and by directly measuring the time course of the increase in torque during the movement. Both methods indicated an average time of 400 msec for attaining peak torque in a movement with a duration of 700 msec. In addition, by displacing the arm from its normal trajectory during the movement, we observed that the arm returned neither to the initial nor to the final equilibrium positions, but to points intermediate between them. We conclude that the processes underlying trajectory formation must be more complex than a simple switch between one equilibrium position and another.
TL;DR: The presence of CCK- and somatostatin-immunoreactive material in GABAergic cortical neurons raises the possibility that neuroactive peptides affect GABAergic neurotransmission.
Abstract: The coexistence of gamma-aminobutyric acid (GABA), glutamate decarboxylase (GAD), and cholecystokinin (CCK)- or somatostatin- immunoreactive material in the same neurons was studied in the hippocampus and visual cortex of the cat. One-micrometer-thick serial sections of the same neuron were reacted to reveal different antigens by the unlabeled antibody enzyme method. All CCK- and somatostatin- immunoreactive neurons in the cortex and all CCK-immunoreactive and the majority of somatostatin-immunoreactive neurons in the hippocampus that could be examined in serial sections were also immunoreactive for GABA. In neurons that were immunoreactive for GAD it was often possible to demonstrate immunoreactivity for one of the peptides as well as for GABA. GABA-immunoreactive neurons, as revealed by an antiserum to GABA, were present in all layers of the cortex and hippocampus, and their shape, size, and distribution were similar to GAD-immunoreactive neurons. All GAD-immunoreactive neurons were also positive for GABA, but the latter staining revealed additional neurons. CCK/GABA- and somatostatin/GABA-immunoreactive neurons were present mainly in layers II and upper III and in layers V and VI in the visual cortex. CCK/GABA- immunoreactive neurons were most frequently present in the strata oriens, pyramidale, and moleculare of the hippocampus and in the polymorph cell layer of the dentate gyrus. Somatostatin/GABA- immunoreactive neurons were localized mainly in the stratum oriens and in the hilus of the fascia dentata. The two peptides could not be found in the same neuron. The majority of neurons that were GABA immunoreactive did not stain for either peptide. The presence of CCK- and somatostatin-immunoreactive material in GABAergic cortical neurons raises the possibility that neuroactive peptides affect GABAergic neurotransmission.
TL;DR: Immunocytochemical studies indicate that DARPP-32, is present in the subclass of dopaminoceptive neurons containing D-1 receptors (dopamine receptors coupled to adenylate cyclase) and may be an effective marker for certain of the actions of dopamine that are mediated through cAMP and its associated protein kinase.
Abstract: Immunocytochemical studies have been carried out to determine the regional and cellular distribution of DARPP-32, a protein the phosphorylation of which can be regulated by dopamine and cAMP in intact cells. These immunocytochemical studies indicate tha DARPP-32 is localized primarily in those brain regions enriched in dopaminergic nerve terminals. Moreover, the staining pattern supports the conclusion that the DARPP-32 is present in dopaminoceptive neurons, i.e., neurons that receive a dopamine input, and that it is absent from the dopaminergic neurons themselves. Within the caudatoputamen, nucleus accumbens, olfactory tubercle, bed nucleus of the stria terminalis, and portions of the amygdaloid complex, all of which receive a strong dopamine input, DARPP-32 immunoreactivity is present in neuronal cell bodies and dendrites. In brain regions that are known to receive projections from these nuclei, puncta (presumed nerve terminals) are strongly immunoreactive for DARPP-32 but indigenous cell bodies and dendrites are not immunoreactive. These target areas include the globus pallidus, ventral pallidum, entopeduncular nucleus, and the pars reticulata of the substantia nigra. No immunoreactivity is detected in neuronal cell bodies or dendrites in any of the dopaminergic nuclei. Furthermore, nerve terminals immunoreactive for DARPP-32 do not resemble dopaminergic varicosities in either their morphology or their pattern of distribution. Many neurons are weakly immunoreactive for DARPP-32 and some of these are found in areas that apparently lack a dopaminergic input: weakly labeled neuronal cell bodies and dendrites were found throughout the neocortex, primarily in layer VI, and in the Purkinje neurons of the cerebellum. DARPP-32 immunoreactivity is also present in certain glial cells, especially in the median eminence, arcuate nucleus, and medial habenula. The present immunocytochemical studies, taken together with biochemical studies (Hemmings, H.C., Jr., A.C. Nairn, D.W. Aswad, and P. Greengard (1984) J. Neurosci. 4: 99-110; Walaas, S.I., and P. Greengard (1984) J. Neurosci. 4: 84-98) on DARPP-32, indicate that DARPP-32, is present in the subclass of dopaminoceptive neurons containing D-1 receptors (dopamine receptors coupled to adenylate cyclase). DARPP-32 may be an effective marker for certain of the actions of dopamine that are mediated through cAMP and its associated protein kinase.
TL;DR: It is demonstrated that lesions of MG and lower auditory centers, but not lesions of the auditory cortex, block autonomic and behavioral conditioned emotional responses coupled to acoustic stimuli and indicate that subcortical rather than cortical efferents of MG sustain these responses.
Abstract: The purpose of this study was to identify the afferent link in the neural pathway which mediates emotional responses coupled to auditory stimuli We evaluated whether autonomic and behavioral responses elicited by acoustic conditioned emotional stimuli are based on afferent information derived from the auditory cortex or from the auditory thalamic relay station, the medial geniculate nucleus (MG), in rats The rat auditory cortex was defined through anterograde neuroanatomical tracing studies involving the injection of HRP into MG Lesions were then placed in the auditory cortex or in MG After 10 to 20 days the rats were subjected to classical fear conditioning trials involving the pairing of a pure tone with electric footshock Changes in mean arterial pressure and heart rate and the duration of immobilization ("freezing") and drink suppression elicited by presentation during extinction trials (no footshock) of the acoustic conditioned emotional stimulus were measured Auditory cortex lesions did not affect the magnitude of the mean arterial pressure or heart rate conditioned responses nor the duration of freezing or drink suppression In contrast, lesions of MG suppressed the magnitude of both the autonomic and somatomotor (behavioral) conditioned emotional responses but did not affect either autonomic or somatic responses elicited by the footshock unconditioned stimulus Lesions of the inferior colliculus, the primary source of afferent input to MG, replicated the effects of MG lesions These findings demonstrate that lesions of MG and lower auditory centers, but not lesions of the auditory cortex, block autonomic and behavioral conditioned emotional responses coupled to acoustic stimuli and indicate that subcortical rather than cortical efferents of MG sustain these responses Our concurrent observation that MG projects to several subcortical areas (central and lateral amygdala; caudate-putamen; ventromedial hypothalamus) involved in emotional behavior and autonomic function suggests hypotheses concerning subsequent links in this emotional processing pathway
TL;DR: Electro microscopic observations reported in this study reveal that a steady rate of granule cell neurogenesis occurs during the first year of a rodent's life, and that newly formed granule neurons in the dentate gyrus of the newborn mouse and adult rat are a result of neuroblast division.
Abstract: Ultrastructural identification of mitotic neuronal precursors beneath the basal hippocampal granule cell layer was made using electron micrographs of [3H]thymidine-labeled cells. Ultrathin sections were obtained by a method that allows serial thin sectioning of reembedded sections previously prepared for light microscopic radioautography. The electron microscopic observations reported in this study reveal: (1) that a steady rate of granule cell neurogenesis occurs during the first year of a rodent's life; (2) that newly formed granule neurons in the dentate gyrus of the newborn mouse and adult rat are a result of neuroblast division; and (3) two distinct classes of mitotic cells can be identified during the peak period of postnatal neurogenesis--those with synapses on their cell bodies and processes and those with no synapses or processes.
TL;DR: It is shown that lesions of the regions of cerebellar cortex projecting to the dentate-interpositus nuclei do not permanently abolish the conditioned response, although the amplitude- time course of the learned response could be affected.
Abstract: Neuronal activity was recorded from regions of the cerebellar cortex and dentate-interpositus nuclei during learning and/or performance of a classically conditioned nictitating membrane (NM-a third eyelid)/eyeblink response in the rabbit. It was found that neurons located within restricted portions of the ansiform lobule and anterior lobe cortical regions and of the dentate-interpositus nuclei respond in relation to the performance of the learned eyeblink response. Furthermore, chronic recordings from the dentate-interpositus nuclei revealed that these responses develop in close relation to the learning of the conditioned eyeblink response. Stimulation of the dentate-interpositus nuclei through the recording electrodes in some cases yielded eyelid closure and NM extension in both trained and untrained animals. Lesion of the axons of the dentate-interpositus nuclei (superior cerebellar peduncle), a manipulation which is known to abolish the learned eyeblink response, abolished the stimulation effect. We have previously reported that lesions of the dentate-interpositus nuclei cause abolition of the learned eyeblink response. In the present study, we report that lesions of the regions of cerebellar cortex projecting to the dentate-interpositus nuclei do not permanently abolish the conditioned response, although the amplitude-time course of the learned response could be affected. These results, together with results of other studies, demonstrate that the medial dentate and/or lateral interpositus nuclei are active during learning and performance of the conditioned eyeblink response, are capable of producing this learned response, and are essential for the learning and retention of the conditioned eyeblink response. Therefore, the medial dentate and/or lateral interpositus nuclei are a part of the essential neuronal circuit involved in the learning and production of the classically conditioned eyeblink response in the rabbit.
TL;DR: The biochemical and histological results obtained indicate that the method is suitable to estimate in the rat the changes in the release of endogenous DA and its metabolites which take place in vivo under administration of centrally acting drug.
Abstract: A method for the estimation in rats of the in vivo release and metabolism of dopamine (DA) is described. The method is based on the dialysis principle and consists of inserting transversally in the striatum a thin (0.2 mm) dialysis tube (Amicon Vitafiber) which is then perfused with Ringer. The Ringer, flowing at a constant rate of 2 microliters/min in the dialysis tube, extracts low molecular weight substances from the surrounding tissue by way of simple diffusion along a concentration gradient. At the distal end of the dialysis tube, the Ringer is collected every 10 to 20 min and directly injected into a high performance liquid chromatographer (HPLC) equipped with reverse phase octadecyl sulfate columns which separate DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These substances are then quantitatively estimated by oxidative electrochemical detection. The basal output of DA is 0.3 pmol/20 min, whereas the outputs of DOPAC and HVA are 60 and 20 pmol/20 min, respectively. In basal conditions the output of DA, DOPAC, and HVA is stable over at least 10 hr. Histological examination of the track left by the dialysis probe in rats after 10 hr of continuous dialysis reveals very little damage and normal neuronal morphology in the vicinity of the dialysis tube. Increase of the K+ concentration in the Ringer to 30 mM produced a sharp, reversible increase of DA output. Both the basal and K+-stimulated release were Ca++ dependent, because omission of Ca++ abolished basal and K+-stimulated DA release. Electrical stimulation of the nigrostriatal DA neurons in the medial forebrain bundle sharply increased DA output. Amphetamine sulfate in low doses (1.0 mg/kg, i.v.) produced a 9-fold increase in DA release and decreased DOPAC and HVA output. alpha-Methyl tyrosine (150 mg/kg, i.v.) reduced within 2 hr DA release to 15% of basal values and in parallel also decreased the output of DOPAC and HVA. Reserpine (5 mg/kg, i.p.) reduced DA release but in a slower fashion than alpha- methyl tyrosine and increased DOPAC and HVA. Pargyline (75 mg/kg, i.p.) produced a 4-fold increase of DA release, while it rapidly brought to zero DOPAC and HVA output. gamma-Butyrolactone (700 mg/kg, i.p.) rapidly and lastingly reduced DA, DOPAC, and HVA output. The biochemical and histological results obtained indicate that the method is suitable to estimate in the rat the changes in the release o f endogenous DA and its metabolites which take place in vivo under administration of centrally acting drug.
TL;DR: The findings suggest that the interaction of axons with the non-neuronal milieu through which they grow may play an important role in regulating fasciculation, a process which has generally been treated as due primarily to axon-axon interactions.
Abstract: We have examined the consequences of surface interactions with glial and nonglial cells on the in vitro growth of CNS neurons. When cerebellar or spinal cord cells were plated onto monolayers highly enriched in cortical astrocytes or sciatic nerve Schwann cells, neurons generally grew as single cells and showed relatively little tendency to aggregate. Similarly, neurites showed little tendency to fasciculate. In contrast, when plated onto fibroblast, heart muscle-fibroblast, or astrocyte-free meningeal monolayers, neurons rapidly aggregated, and neurite outgrowth was primarily in large fascicles. There were no glia detectable in the majority of aggregates or fascicles, suggesting that aggregation and fasciculation were due to interactions between neurons. Neurite outgrowth over 24 hr was also greater on astrocytes than on nonglia. Whether or not aggregation and fasciculation occurred was due to surface properties of the glial and nonglial cells. When neurons were added to astrocyte and nonglial monolayers growing in medium conditioned by a large excess of co-cultured nonglia or astrocytes, respectively, the pattern of neuronal growth was determined by the type of monolayer with which the neurons were in contact. Moreover, the initial growth of neurons on heat-killed astrocytes was indistinguishable from growth on living astrocytes. The pattern of neuronal growth on these different monolayers suggests that neurons are more adherent to glia than to other neurons but are more adherent to other neurons than to nonglia. Such an adherence hierarchy could explain the consistent finding of an apposition of neurons to glial surfaces during neuronal migration and axon outgrowth. Our findings also suggest that the interaction of axons with the non-neuronal milieu through which they grow may play an important role in regulating fasciculation, a process which has generally been treated as due primarily to axon-axon interactions.
TL;DR: The appearance of neurofilaments (NFs) and vimentin (Vim) in the nervous system of the mouse embryo was documented using immunohistochemical techniques and correlates extremely well with neurofibrillar differentiation and with the expression of adrenergic neurotransmitter properties.
Abstract: The appearance of neurofilaments (NFs) and vimentin (Vim) in the nervous system of the mouse embryo was documented using immunohistochemical techniques. The three NF protein subunits appear early and simultaneously in central and peripheral neurons at 9 to 10 days of gestation. The onset of NF expression is concomitant with axon elongation and correlates extremely well with neurofibrillar differentiation and, in the case of autonomic ganglia, with the expression of adrenergic neurotransmitter properties. In the central and peripheral nervous system, NF expression is preceded by that of Vim, and both types of intermediate filaments coexist within the same cell for a short period of time.
TL;DR: It is concluded that dopamine decreases the permeability of the gap junctions between the axon terminals of the H1 horizontal cells of the turtle retina and that this action probably involves cyclic AMP as a second messenger.
Abstract: The axon terminals of the H1 horizontal cells of the turtle retina are electrically coupled by extensive gap junctions. Dopamine (10 nM to 10 microM) induces a narrowing of the receptive field profile of the H1 horizontal cell axon terminals, increases the coupling resistance between them, and decreases the diffusion of the dye Lucifer Yellow in the network formed by the coupled axon terminals. These actions of dopamine involve the activation of D1 receptors located on the membrane of the H1 horizontal cell axon terminals proper. Increases of the intracellular cyclic AMP concentration induced by either stimulating the adenylate cyclase activity with forskolin or inhibiting the phosphodiesterase activity with isobutylmethylxanthine, theophylline, aminophylline, or compound RO 20-1724 elicit effects similar to those of dopamine on the receptive field profile of the H1 horizontal cell axon terminals, on their coupling resistance, and on the diffusion of Lucifer Yellow in the axon terminal network. It is concluded that dopamine decreases the permeability of the gap junctions between the axon terminals of the H1 horizontal cells of the turtle retina and that this action probably involves cyclic AMP as a second messenger.
TL;DR: Neurons immunoreactive for either peptide are found in all areas of monkey cortex examined as well as throughout the rat cerebral cortex and in the subcortical white matter of both species.
Abstract: Neurons in the monkey and rat cerebral cortex immunoreactive for somatostatin tetradecapeptide (SRIF) and for neuropeptide Y (NPY) were examined in the light and electron microscope. Neurons immunoreactive for either peptide are found in all areas of monkey cortex examined as well as throughout the rat cerebral cortex and in the subcortical white matter of both species. In monkey and rat cortex, SRIF-positive neurons are morphologically very similar to NPY-positive neurons. Of the total population of SRIF-positive and NPY-positive neurons in sensory-motor and parietal cortex of monkeys, a minimum of 24% was immunoreactive for both peptides. Most cell bodies are small (8 to 10 micron in diameter) and are present through the depth of the cortex but are densest in layers II-III, in layer VI, and in the subjacent white matter. From the cell bodies several processes commonly emerge, branch two or three times, become beaded, and extend for long distances through the cortex. The fields formed by these processes vary from cell to cell; therefore, the usual morphological terms bipolar, multipolar, and so on do not adequately characterize the full population of neurons. Virtually every cell, however, has at least one long vertically oriented process, and most processes of white matter cells ascent into the cortex. No processes could be positively identified with the light microscope as axons. The processes of the peptide-positive neurons form dense plexuses in the cortex. In each area of monkey cortex, SRIF-positive and NPY-positive processes form a superficial plexus in layers I and II and a deep plexus in layer VI. These plexuses vary in density from area to area. All appear to arise from cortical or white matter cells rather than from extrinsic afferents. In some areas such as SI and areas 5 and 7, the superficial plexus extends deeply into layers III and IV; and in area 17, two very prominent middle plexuses occur in layers IIIB through IVB and in the upper one-third of layer V; these are separated by layer IVC, a major zone of thalamic terminations, which contains very few SRIF- or NPY-positive processes. The density of the plexuses is greater for NPY-positive processes than for SRIF-positive processes in all areas. In the rat, the plexuses do not display a strict laminar organization but generally are densest in the supragranular layers (I to III) and decline steadily in the deeper layers.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: The results imply that SMA may give rise normally to discharges informing the contralateral hemisphere of intended and/or ongoing movements via the corpus callosum, which may prevent duplication of responses during unimanual tasks and help to coordinate the behavior of both hands during a bimanual task.
Abstract: The short-term and long-term behavioral effects of unilateral lesions of the supplementary motor area (SMA) were studied in five monkeys (Macaca fascicularis ssp). A monkey with a unilateral lesion of the premotor area (PM) served as a control. In all animals, general behavior was unaffected by the lesions. For a few weeks postoperatively, all monkeys showed a clumsiness of forelimb movements, bilaterally, which involved both the distal and proximal muscles. Two SMA-lesioned monkeys (but not the PM-lesioned one), studied for up to 1 year postoperatively, showed a characteristic deficit of bimanual coordination where the two hands tended to behave in a similar manner instead of sharing the task between them. This deficit was more pronounced after a lesion contralateral to the nonpreferred hand. The deficit was interpreted as indicating that the intact SMA now influenced the motor outflow of both the ipsilateral hemisphere and the contralateral one through the corpus callosum. Callosal section immediately abolished the bimanual deficit, although the clumsiness returned transiently. The results imply that SMA may give rise normally to discharges informing the contralateral hemisphere of intended and/or ongoing movements via the corpus callosum. This may prevent duplication of responses during unimanual tasks and help to coordinate the behavior of both hands during a bimanual task.
TL;DR: It is demonstrated that a variety of protein synthesis inhibitors are able to block the production of LTP in field CA1, suggesting the necessity for a set of newly synthesized or rapidly turned over proteins for hippocampal LTP.
Abstract: Long-term potentiation (LTP) in the hippocampus has attracted attention as a model of neuronal plasticity in the central nervous system. Although accumulating evidence associates protein synthesis with LTP, there is no direct proof that protein synthesis is actually required for the production of LTP. Therefore, we have examined the ability of some inhibitors of protein synthesis to modify LTP in the CA1 region of the rat hippocampal slice. Incubation for 30 min in the presence of emetine, cycloheximide, or puromycin decreased the frequency of occurrence of LTP in field CA1 elicited by repetitive stimulation of the Schaffer collaterals. This blockade was dose dependent and correlated with the ability of individual inhibitors to inhibit incorporation of [3H]valine into proteins. LTP blockade was irreversible for the irreversible inhibitor emetine and was reversible for the reversible inhibitor cycloheximide. Blockade of LTP required a substantial preincubation period to be effective. Even at the highest concentration of emetine used to block LTP, no effect on any intracellularly recorded membrane properties was observed. In contrast, the protein synthesis inhibitor anisomycin was unable to block LTP. Puromycin aminonucleoside, a structural analogue of puromycin which is inactive in inhibiting protein synthesis, was ineffective in blocking LTP. These experiments demonstrate that a variety of protein synthesis inhibitors are able to block the production of LTP in field CA1, suggesting the necessity for a set of newly synthesized or rapidly turned over proteins for hippocampal LTP.
TL;DR: The results suggest that protoplasmic and fibrous astrocytes are distinct classes of glial cells that differ in their antigenic phenotype and developmental history, as well as in their morphology and location within the CNS.
Abstract: We have studied semithin frozen sections of developing and adult rat central nervous system (CNS) by indirect immunofluorescence in order to determine the antigenic phenotype of protoplasmic and fibrous astrocytes. Using antibodies against glial fibrillary acidic protein (GFAP) to identify astrocytes, we show that the great majority of fibrous astrocytes in adult optic nerve are labeled by the monoclonal antibody A2B5, while the great majority of protoplasmic astrocytes in adult cerebral cortex are not. Astrocytes located at the periphery of the adult optic nerve that form the glial limiting membrane are more like protoplasmic astrocytes than fibrous astrocytes in that they strain relatively weakly with anti-GFAP antiserum and are A2B5-. In the developing rat optic nerve, protoplasmic-like astrocytes appear at least one week before the first fibrous astrocytes can be detected. Taken together with our previous observations on astrocytes in suspensions and cultures of developing rat optic nerve (Raff, M.C., E.R. Abney, J. Cohen, R. Lindsay, and M. Noble (1983) J. Neurosci. 3: 1289–1300; Raff, M.C., R.H. Miller, and M. Noble (1983) Nature 303: 390– 396), these results suggest that protoplasmic and fibrous astrocytes are distinct classes of glial cells that differ in their antigenic phenotype and developmental history, as well as in their morphology and location within the CNS.
TL;DR: Observations of hippocampal neurons in dissociated cell culture show that the fundamental differences in form and in the distribution of ribosomes between axons and dendrites can be established in cell culture.
Abstract: We have studied the processes which are elaborated by hippocampal neurons in dissociated cell culture. Nerve cells, which were obtained from fetal rats at 18 to 20 days of gestation, were plated at very low density onto polylysine-treated coverslips and were maintained in serum-free medium. Under such conditions, some cells develop without contacting any neighboring neurons or glial cells. Examples of such isolated cells which had developed for 1 week in culture were studied first by light microscopy, then they were sectioned parallel to the substratum so that all portions of the cell and its processes could be examined by electron microscopy. Dendrites and axons could be clearly distinguished by both light and electron microscopy. Dendrites were rather thick at the base but tapered rapidly to a minimum diameter of about 0.5 micron and contained polyribosomes throughout their length. Axons, which were several times longer than the dendrites, were thinner at the origin, tapered much less, and were essentially ribosome-free. These ultrastructural differences were particularly obvious at branch points, where cytoplasmic organelles tend to accumulate. Clusters of polyribosomes were invariably present at dendritic branch points, but they were never observed at axonal branch points. The axons most commonly arose from the proximal portion of a dendrite rather than directly from the cell body as they typically do in situ. These observations show that the fundamental differences in form and in the distribution of ribosomes between axons and dendrites can be established in cell culture. Contact with afferent fibers or with target cells during the period of process outgrowth is unnecessary for the expression of these features of axonal and dendritic differentiation.
TL;DR: Quantitative autoradiography provides an extremely sensitive assay which can be used to gather detailed pharmacological and anatomical information about L-[3H]glutamate binding in the central nervous system.
Abstract: Quantitative autoradiography was used to determine the distribution of L-[3H]glutamate-binding sites in the rat central nervous system. Autoradiography was carried out in the presence of Cl- and Ca2+ ions. Scatchard plots and Hill coefficients of glutamate binding suggested that glutamate was interacting with a single population of sites having a K-D of about 300 nM and a capacity of 14.5 pmol/mg of protein. In displacement studies, ibotenate also appeared to bind to a single class of non-interacting sites with a KI of 28 microM. However, quisqualate displacement of [3H]glutamate binding revealed two well-resolved sites with KIS of 12 nM and 114 microM in striatum. These sites were unevenly distributed, representing different proportions of specific glutamate binding in different brain regions. The distribution of glutamate- binding sites correlated very well with the projection areas of putative glutamatergic pathways. This technique provides an extremely sensitive assay which can be used to gather detailed pharmacological and anatomical information about L-[3H]glutamate binding in the central nervous system.
TL;DR: The intermediate and deep layers of the cat's superior colliculus are examined for evidence of a neural representation of auditory space and the responses of single units to sounds presented in a free field support the following generalizations.
Abstract: We have examined the intermediate and deep layers of the cat's superior colliculus for evidence of a neural representation of auditory space. We measured the responses of single units to sounds presented in a free field. The results support the following generalizations. Most auditory units in the superior colliculus have sharply delimited receptive fields which form two discrete classes distinguished by their locations and sizes. The remaining units respond to sounds presented at any location. Each auditory unit responds maximally to sounds at a particular horizontal and vertical location within its receptive field, the unit's “best area.” The best areas and receptive field borders of a unit are resistant to changes in the intensity of stimulus. The locations of best areas shift systematically as a function of unit position to form a continuous map of auditory space. The horizontal dimension of space is mapped rostrocaudally, and the vertical dimension is mapped mediolaterally. This map corresponds in orientation with the map of visual space. These data permit us to infer the distribution of unit activity elicited by a sound at any given location. Regardless of its location, a sound activates a substantial portion of the superior colliculus. Indeed, sounds at some locations activate nearly all of the auditory units. However the activated portion of the colliculus contains a restricted region of units which are excited to near their maximum firing rates. The position of this focus of greatest activity varies systematically according to the location of the sound source, thus mapping the location of the sound in space.
TL;DR: The localization of MAP2 in dendritic spines and in the psd suggests that this protein may have a biological role independent of its association with microtubules, and the observations on differential staining of the hybridoma antibodies against MAP2 suggest that there may be distinct subtypes or states ofMAP2 within neurons.
Abstract: The distribution and subcellular localization of tubulin and MAP2 in brain tissue were analyzed by immunocytochemistry with monoclonal hybridoma antibodies prepared against Chinese hamster brain tubulin and MAP2. We examined three anti-tubulin hybridoma antibodies (Tu3B, Tu9B, Tu12) specific for beta-tubulin, and two anti-MAP2 hybridoma antibodies (AP9,AP13). The specificity of each of the monoclonal antibodies was characterized by staining nitrocellulose electrophoretic blots of SDS-polyacrylamide gels of whole brain or hippocampal extracts. Each hybridoma antibody bound only its respective antigen in these preparations. Polyclonal antisera against tubulin were also examined. Sections reacted with antisera against tubulin or monoclonal antibodies against beta-tubulin revealed a wide variety of stained cellular compartments. The reaction product was found to decorate dendritic and axonal microtubles in neurons; glial cells were also stained. MAP2 immunoreactivity was found only in neurons. In the case of one of the monoclonal antibodies (AP9), staining was preferentially associated with dendritic processes. However, light but significant staining of axonal processes was seen with AP13. Within dendrites, MAP2 was found associated with dendritic microtubules and postsynaptic densities (psd), both in shaft and spine synapses. In addition, strong immunoreactivity for MAP2 was found within the cytoplasm of dendritic spines. There was little or no immunoreactivity for tubulin in the spine cytoplasm, although the psd was stained. The localization of MAP2 in dendritic spines and in the psd suggests that this protein may have a biological role independent of its association with microtubules. The observations on differential staining of the hybridoma antibodies against MAP2 suggest that there may be distinct subtypes or states of MAP2 within neurons.
TL;DR: The clear difference between the two nuclei in sensitivity to both phase and intensity and the reciprocity in response properties support the hypothesis that each nucleus is specialized to process one parameter (phase or intensity) and not the other.
Abstract: The cochlear nucleus of the barn owl is composed of two anatomically distinct subnuclei, n. magnocellularis (the magnocellular nucleus) and n. angularis (the angular nucleus). In the magnocellular nucleus, neurons tend to respond at a particular phase of a stimulus sine wave. Phase locking was observed for frequencies up to 9.0 kHz. The intensity- spike count functions of magnocellular units are characterized by high rates of spontaneous activity, a narrow range of intensities over which spike counts changed from spontaneous to saturation levels, and a small increase in spike counts with intensity over that range. In the angular nucleus, neurons showed little or no tendency to respond at a certain sinusoidal phase, although some showed weak phase locking for frequencies below 3.5 kHz. Angular units typically had low spontaneous rates, large dynamic ranges, and large increases in spike counts with intensity, resulting in high saturation levels. The clear difference between the two nuclei in sensitivity to both phase and intensity and the reciprocity in response properties support the hypothesis that each nucleus is specialized to process one parameter (phase or intensity) and not the other.
TL;DR: Results suggest that microtubules with different molecular compositions are present in the cerebellum where they are distributed differently between cells as well as within the same cell.
Abstract: The distribution of microtubule-associated proteins (MAPs) 1 and 2 in rat brain was studied using monoclonal antibodies. Immunochemical staining showed that both MAP1 and MAP2 are present only in neurons and both are highly concentrated in dendrites compared to axons. Otherwise, they differed in distribution in various ways. MAP1 was present at low levels in axons, whereas MAP2 was never detectable in axons with either of two different fixation methods used. In the cerebellum the two MAPs differed in relative concentration in various classes on neurons. Thus, anti-MAP1 staining was strong in Purkinje cells but very faint in granule cells, whereas anti-MAP2 staining was strong in both. There were also distributional differences within the same cell. Thus, in Purkinje cells, anti-MAP1 staining is strong in the cell body, initial axon segment and throughout the dendritic tree, but anti-MAP2 staining is present only in dendrites beyond the initial proximal portion. These results suggest that microtubules with different molecular compositions are present in the cerebellum where they are distributed differently between cells as well as within the same cell.