Cortical Terminals Research Articles

Distribution and synaptic contacts of the cortical terminals arising from neurons in the rat ventromedial thalamic nucleus

Injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin within the ventromedial thalamic nucleus resulted in many filled fibres in the frontal areas of rat cerebral cortex. The fibres were restricted to the upper part of layer I except in a small area of motor cortex where terminals were also found in deeper layers. Terminals were also seen in the striatum, in parts of the mesencephalic reticular formation and occasionally in the contralateral ventromedial nucleus. There is some topographical order in the projection with medial and dorsal areas well represented in medial cortex while lateral parts of ventromedial nucleus are more directly related to the cortical area that receives the ventrolateral thalamic nucleus projection. Electron microscopic examination showed the terminals in layer I of cortex making synaptic contact with dendritic spines and small dendritic profiles that showed a very dense postsynaptic specialization. Neurons in the ventromedial nucleus could be antidromically driven from electrode positions along strips of cortex which could not be easily related to any known organizational pattern in the cortex. Thalamic neurons responding antidromically to only one stimulation site were more common when the stimulation was within motor cortical areas, suggesting that in this region a more restricted pattern of termination is the rule.

The GABA-immunoreactive neurons in the interlaminar regions of the cat lateral geniculate nucleus: light and electron microscopic observations.

GABA-immunoreactive cells located in the interlaminar zone between the A and A1 laminae of cat LGN were studied at the LM and EM levels. The mean perikaryal size of these neurons was larger than that of GABA-immunoreactive cells in the A-laminae of LGN. Interlaminar GABA+ cells examined in plastic semithin sections of LGN after massive injections of HRP in the striate and extrastriate visual cortex were not retrogradely labeled with reaction products (as previously reported for the GABA+ cells in the laminar regions of LGN) suggesting that these cells do not project to the visual cortex. Serial EM analysis of two partially reconstructed interlaminar GABA+ cells showed that they receive synaptic inputs from RLD terminals of axon collaterals of geniculo-cortical relay cells, from cortical (RSD) terminals, from inhibitory (F) axon terminals, and from other undetermined terminals, but not from retinal (RLP) axon terminals. These data suggest that the GABAergic cells in the interlaminar zones of LGN participate as interneurons in recurrent inhibitory circuits in LGN. The synaptic inputs to these cells and ultrastructural features, notably somatic spines and dendrites oriented predominantly orthogonal to the projection lines in LGN, are similar to those of neurons of the perigeniculate nucleus.

Stimulation of the nucleus basalis of Meynert increases acetylcholine release in the cerebral cortex in rats

The effect of focal stimulation of the magnocellular nucleus of the basal forebrain (nucleus basalis of Meynert; NBM) on acetylcholine (ACh) release in the cerebral cortex in the parietal lobe was examined in halothane-anesthetized rats. ACh was measured using a microdialysis method. Focal electrical stimulation of the unilateral NBM increased ACh release in the ipsilateral cerebral cortex in stimulus intensity and frequency dependently. Microinjection of L-glutamate (100 nmol) into the unilateral NBM also increased ACh release in the ipsilateral cerebral cortex. The ACh release in the contralateral cerebral cortex was not affected by these unilateral stimulations of the NBM. It was concluded that focal stimulation of the NBM releases ACh from cortical terminals of cholinergic fibers originating in the NBM.

Ultrastructural identification of synaptic terminals from cortical axons and from collateral axons of geniculo-cortical relay cells in the perigeniculate nucleus of the cat.

Electron microscopic analysis of sections of the perigeniculate nucleus (PGN) of the cat processed with horseradish peroxidase (HRP) histochemistry after massive injections of this enzyme in the visual cortex showed two types of synaptic terminals labeled with HRP reaction products. One type (RLD terminals) is characterized by round synaptic vesicles, large size, dark mitochondria and asymmetrical synaptic contacts with somata and dendrites. The second type (RSD terminals) is characterized by round synaptic vesicles, small size, dark mitochondria and asymmetrical synaptic contacts with dendrites. The HRP+ RSD terminals, which were also found in the dorsal lateral geniculate nucleus (LGN), are interpreted as terminals of cortical origin both in the PGN and LGN, since previous studies have identified cortical terminals as being of RSD type in the LGN and in other thalamic nuclei. The HRP+ RLD terminals are interpreted as synaptic terminals of collaterals axons of geniculocortical relay cells in the PGN labeled by retrograde transport of HRP from the cortex. In addition, in semithin and ultrathin sections somata in the PGN were never found labeled with HRP products indicating the absence of a PGN projection to the visual cortex.

Restoration of the corticostriatal projection in rat neostriatal grafts: electron microscopic analysis

The corticostriatal projection in rat neostriatal grafts was studied by using the axonal transport of Phaseolus vulgaris-leucoagglutinin. The neostriatal primodia from 15–18-day embryos were used to make a cell suspension which was implanted unilaterally into the rat neostriatum 3–5 days after kainic acid lesion. Two to four months later, regions of the frontal cortex ipsilateral to the grafts were injected iontophoretically with Phaseolus valgaris-leucoagglutinin. There were many Phaseolus valgaris-leucoagglutinin labeled cortical fibers in the host neostriatum. Although the density of labeled fibers in the grafts was much lower than that in the surrounding host tissue, some fibers could be seen to enter the grafts and form terminal arborizations. The morphology of labeled fibers in the graft differed from that of corticostriatal fibers from the same injection but distributing in the host neostriatum. The labeled fibers in the host neostriatum arborized in an extended pattern, branching infrequently and making most of their synapses en passant at varicosities along their courses. The labeled fibers in the grafts made more dense arborizations with many short branches that formed clusters of terminals confined to small foci along their courses. The cellular composition and the structure of the neuropil in the neostriatal grafts were similar to that of the neostriatum. As those in the host, labeled corticostriatal terminals in the grafts contained densely packed round vesicles and made asymmetric synapses on dendritic spines, dendritic shafts and somata. A quantitative analysis, however, revealed that the distribution of postsynaptic elements of labeled boutons in the grafts was different from that in the hosts. More than 90% of the labeled cortical terminals in the host neostriatum contacted dendritic spines whereas only 47% of the labeled terminals in the grafts contacted spines, and 50% of them terminated on the dendritic shafts. The present study provides direct anatomic evidence to demonstrate the restoration of the corticostriatal projection in grafts. The difference in the distribution of postsynaptic elements in the grafts and the hosts may represent a response to the decreased innervation density of cortical inputs to the graft tissue, and may contribute to the recovery of corticostriatal responses by increasing the effectiveness of transmission by the fibers that do grow into the graft and form contacts there.

Compartmentation of Ca2+ -dependent pools of glutamate and aspartate in isolated cerebral cortical nerve terminals by isotopic exchange and fractionation

1.-Glutamate is a major excitatory neurotransmitter in the central nervous system and can be released in a Ca?+dependent manner from isolated nerve terminals (synaptosomes). lmmunocytochemical (Storm-Mathison et al., 1983) and fractionation (Naito & Ueda, 1983) studies suggest the cxistencc of a vesicular pool of glutamate within the synaptosome. While this allows for the possibility that glutamate may be released by exocytosis. the alternative that such vcsicles merely play a storage role, and that Ca? +-dependent release occurs from the cytoplasm presumably via Ca? + dependent plasma membrane channels ( D e Belleroche & Bradford, 1077) has also been advanced. In this paper we show that externally added [‘JC]glutamatc equilibrates with the Ca”-dependent pool much more slowly than with the cytoplasm. and also that externally added [ lJC]glutamate equilibrates slowly with a pool of glutamate which is resistant t o the hypo-osmotic lysis o f the synaptosomal plasma membrane. suggesting that the Ca?’-dependent pool can be identified with the hypo-osmotically resistant, presumably vesicular. pool. 11-1 ”H laspartate does not equilibrate with this Ca’ +-dependent releasable pool. Guinea-pig cerebral cortical synaptosornes were labelled by incubation for 3, IS or 30 min with 0.85 pCi o f L[ ‘JCjglutamate/mg o f synaptosomal protein and 3.4 pCi of D[ 7H laspartate/mg. and then diluted into incubation mcdia containing 4 0 mM-KCI and either 1.73 mM-CaCl, o r 2.67 mM-EGTA. This depolarization in the presence or absence o f Ca?+ was stopped after 1 min by centrifugation through silicone oil for 1 min. Samples were extracted, endogenous glutamate and aspartate determined by h.p.1.c. analysis, and the [ “Clglutarnate and [‘Hlaspartate in the peaks measured by liquid scintillation counting. From these data, the Ca? + -

Pharmacokinetics and pharmacodynamics of acetylcholinesterase inhibition: Can acetylcholine levels in the brain be improved in alzheimer's disease?

AbstractUp to 20% or more of individuals who will be 80 years of age will develop senile dementia of the Alzheimer type (SDAT). In SDAT patients cholinergic neurons in the basal forebrain undergo profound damage, which is reflected in decreased acetylcholine synthesis, choline acetyltransferase activity, acetylcholinesterase activity, and choline uptake in cortical terminals. Physostigmine has been widely used to increase brain acetylcholine concentration by inhibiting acetylcholinesterase. The pharmacokinetics of physostigmine and its effects on acetylcholine concentration are not well studied. Our studies of physostigmine pharmacokinetics in dogs, rats, and humans suggest that a “slow‐release formulation” may be necessary to achieve increases in acetylcholine concentrations that will have therapeutic effects in SDAT. To investigate one potential “slow release formulation” of physostigmine we have studied direct injection into the lateral ventricles of the brain.

Cytodifferentiation and developing neuronal circuitry in the human lateral geniculate nucleus

The developing neural substrate in dorsal lateral geniculate nucleus of human fetuses and premature, full-term and postnatal infants, has been analysed using rapid Golgi impregnation, computerized image analysis, electronmicroscopy, and immunocytochemical method for localization of γ-aminobutyric acid. Nuclear and cytoplasmic neuronal maturation is observed to extend over the entire period studied. Axodendritic synapses, presumably of retinal origin, are occasionally seen at 13–14 fetal weeks. They become increasingly apparent at 18–19 weeks. Dendrodendritic contacts are visualized at 15 weeks. Cortical terminals and occasional triadic contacts are evident around 21 weeks. The inhibitory interneurons containing γ-aminobutyric acid are present in small numbers at 15–16 weeks; their numerical density increases considerably at 17 weeks but decreases thereafter. The presence of γ-aminobutyric acid containing nerve cells and synaptic triads is indicative of the formation of inhibitory circuitry. At 15–16 weeks neurons are mostly bipolar although different forms of multipolar cells may be seen. By 24 weeks the radiated and bitufted multipolar neurons, neurons with beaded dendrites and neurons with axon-like dendritic processes are identifiable. There are no apparent differences in differentiation of neurons between the cranial and caudal parts of dorsal lateral geniculate nucleus. At 15–16 weeks, however, the cells of prospective magnocellular zone appear to be more mature than do the cells in the parvocellular zone. The neuronal soma increases continuously in size. Dendrite development starts at 15–16 weeks of gestation, thereafter the increase in number of their branches and their length is observed. Between 15–16 and 24 weeks, spines and filiform processes appear first on the proximal shafts of the dendrites and subsequently on their distal portion. There is increase in the number of filiform processes and hair-like appendages on geniculate neurons of premature infants born at 32 and 37 weeks of gestation and of a 4-day postnatal infant. Computerized quantitative data substantiate the progressive increase in growth parameters. The significance of comparative and functional aspect of the data is discussed.

Evidence for reactive synaptogenesis in the ventrolateral thalamus and red nucleus of the rat: changes in high affinity glutamate uptake and numbers of corticofugal fiber terminals.

High affinity glutamate uptake into corticofugal fiber terminals was measured in the ventrolateral thalamus and red nucleus at varying time intervals after lesions were made by kainic acid in the contralateral interpositus nucleus of the cerebellum in rats. Under similar conditions the density of cortical fiber terminals was estimated using the Fink-Heimer impregnation technique. 1. Glutamate uptake steadily increased in the ventrolateral thalamus up to 60 days after lesions in the contralateral cerebellum. 2. Similar changes were noted in the red nucleus. 3. The changes were dependent on the integrity of corticofugal fibers to the thalamus and red nucleus. 4. No changes in uptake of gamma-aminobutyric acid were noted. 5. Saturation curves for glutamate uptake suggested a change in the maximal number of transport sites. 6. Fink-Heimer degeneration studies showed an increase in cortical terminals in the ipsilateral ventrolateral thalamus and in both rostral and caudal regions of the red nucleus following lesions in the contralateral interpositus nucleus. The data are consistent with an increase in the number of cortical fiber terminals in reaction to loss of cerebellar input to the ventrolateral thalamus and red nucleus. This study correlates anatomical and biochemical evidence for collateral sprouting in a model based on electrophysiologic data in the red nucleus and extends the model to include the thalamus.

Reorganization of Pericruciate cortical projections to the spinal cord and dorsal column nuclei after neonatal or adult cerebral hemispherectomy in cats

This is a quantitative study of changes in distribution and density of terminals of the corticospinal tract in the cervical spinal cord and dorsal column nuclei (DCN) in cats with left cerebral hemispherectomy performed neonatally or in adulthood. Kittens received hemispherectomy at a mean of 12.1 postnatal days and were compared, as adults, to adult-lesioned cats of similar survival time. All animals, including controls, received injections of [ 3H]leucine-proline and were sacrificed 5 days later. Injection sites and terminal fields were reconstructed from autoradiography-processed tissue. The label filled comparable extents of areas 4γ and 3a of the right cerebral cortex. Coronal sections from upper and lower cervical cord levels, and from the brainstem (cuneate and gracile nuclei) were studied. Computer-image processing procedures were used to count labeled particles from multiple sites of the dorsal horn and DCN, bilaterally. In the spinal cord of intact and adult-hemispherectomized cats, most terminals were found in lamina VI, and adjacent laminae V and VII contralateral to the injection side. The major finding was that neonatal-lesioned cats showed a significant increase in axon terminals in areas ipsilateral to the injection. The topography of distribution of the novel terminals was similar to that in the contralateral side and the originating fibers appeared to have crossed the midline from that side. A similar reorganization occurred in the gracile nucleus where, in intact and adult-lesioned cats, the cortical terminals also predominated in the side contralateral to the injection. In contrast, neonatal-lesioned animals showed a significant increase in terminal density ipsilateral to the cortical injection. These findings are discussed as an alternative mechanism for postlesion remodeling of the corticospinal tract in animals with the pyramidal crossing completed at the time of birth.

Direct cortical projections to the parabrachial nucleus in the cat.

Direct projections from the cerebral cortex to the parabrachial nucleus in the cat were examined by the horseradish peroxidase (HRP)method. When HRP was injected into the parabrachial nucleus, retrogradely labeled neuronal cell bodies were seen, bilaterally with an ipsilateral predominance, mainly in the orbital gyrus, the lateral bank of the presylvian sulcus, and a restricted region in the infralimbic cortex on the medial surface of the frontal lobe (stereotaxic coordinates; Fr: 22, L: 1, H: -1); all labeled neurons were in deep pyramidal cell layer. After injecting HRP conjugated to wheat germ agglutinin (WGA-HRP) into the cortical regions where retrogradely labeled neurons were found after injecting HRP into the parabrachial nucleus, anterogradely labeled cortical fibers were traced to the parabrachial nucleus. Corticoparabrachial fibers originating from the orbital gyrus and the lateral bank of the presylvian sulcus ran ipsilaterally through the internal capsule and the cerebral peduncle down to the lower brainstem, whereas those from the infralimbic cortex coursed down ipsilaterally through the medial forebrain bundle. These cortical fibers to the parabrachial nucleus were distributed bilaterally with an ipsilateral predominance. Cortical fiber terminals in the parabrachial nucleus were topographically arranged: Corticoparabrachial fibers from the lateral bank of the presylvian sulcus ended most massively in the dorsal part of the lateral parabrachial nucleus. Corticoparabrachial fibers from the orbital gyrus ended most heavily in the medial parabrachial nucleus and less heavily in the lateral parabrachial nucleus. Corticoparabrachial fibers from the infralimbic cortex ended mostly in the parabrachial regions surrounding the brachium conjunctivum.

An EM-autoradiographic analysis of the projection from cortical areas 17, 18, and 19 to the superior colliculus in the cat.

The electron microscopic autoradiographic method was used to identify terminals of axons from cortical areas 17, 18, and 19 in the superficial layers of the superior colliculus. The results show that terminals of area 17 neurons contain round vesicles and made asymmetrical synaptic contacts predominantly onto one or more dendrites or dendritic appendages. Some profiles postsynaptic to labeled terminals contain vesicles and presumably are involved in serial synaptic arrangements. Terminals of area 18 and 19 neurons in the superficial collicular layers appear to comprise two populations, one similar in most respects to area 17 terminals, containing round vesicles and making asymmetrical contacts. The other contains pleomorphic vesicles and makes symmetrical contacts upon dendrites and dendritic appendages. These terminals rarely contact more than one postsynaptic profile, and rarely do the postsynaptic profiles contain vesicles. The two populations of area 18 and 19 terminals containing round and pleomorphic vesicles, respectively, are present in the ratio of approximately 3:1, although this ratio varies throughout the sublaminae of the superficial collicular layers. The presence of two distinct types of cortical terminals in the colliculus suggests that cortical modulation of collicular processing is more complex than was previously conceived.

Corticotectal terminals in the superior colliculus of the rabbit: a light- and electron microscopic analysis using horseradish peroxidase (HRP)-tetramethylbenzidine (TMB).

The projection from the striate cortex to the superior colliculus was studied light- and electron microscopically by means of anterogradely transported horseradish peroxidase and tetramethylbenzidine histochemistry. Labeled boutons were found in the stratum zonale (SZ) and in the stratum griseum superficiale (SGS), not in stratum opticum (SO). There are two maxima of frequency of labeled boutons, one in middle SGS at about 500 microns depth, and a smaller one in upper SGS at about 200 microns depth. Such a bimodal distribution of corticotectal terminals has not been described in any species before. Labeled myelinated axons were found in SGS and SO with a maximal frequency in middle SGS at about 400 microns depth. The myelinated axons in SZ, which are commonly considered to be of cortical origin, were not labeled. The labeled cortical terminals contained numerous round synaptic vesicles and predominantly dark mitochondria. They formed usually asymmetrical synapses and contacted dendrites, some of which contained synaptic vesicles. Occasionally, labeled boutons were observed which definitely did not belong to the type that is generally considered to be of cortical origin.

Differential affinity of dopaminergic agonists and antagonists for D 1 and D 2 dopamine receptors in rat striatum

Dopamine (DA) receptors have been classified into two types, D1 and D2, on the basis of their pharmacological specifities and localization. We now report that lesions of striatal dopaminergic neurons by kainic acid (KA) injection or cerebral neocortex (CN) ablation, differentially affect the potency of DA agonists and antagonists in displacing 3H-spiroperidol specific binding. In particular, agonists show a preferential affinity in displacing 3H-spiroperidol from those receptors situated on intrastriatal neurons, following CN lesion. On the other hand, antagonists show a higher displacing activity for those receptors mainly located on cortical terminals following KA lesion. These data support the hypothesis of the existence of different types of DA receptors with a differential anatomical location.

Patterns of convergence and divergence of retinal and cortical synaptic terminals in the cat superior colliculus

The spatial distributions of retinal and area 17 synapses in the zonal, superficial gray, and upper optic layers of the cat superior colliculus have been examined quantitatively. The colliculus was systematically sampled throughout its rostral-caudal extent. The position of every retinal and ipsilateral area 17 synaptic terminal was mapped with a computer microscope plotter. From these plots, the depth, medial-lateral position, and synaptic density were calculated. Retinal terminals (RT) were identified by their characteristic pale mitochondria, cortical terminals (CT) by degeneration after area 17 lesions. Of 14,939 plotted terminals, 58% were retinal, 42% from area 17. The two sets of synapses were partially segregated along both the dorsal-ventral and rostral-caudal planes of the colliculus. In the dorsal ventral plane, nearly 2/3 of RT were concentrated in a dense band within the upper superficial gray layer. The remainder were lightly distributed throughout the deep superficial gray and upper optic layers. By contrast, almost 3/4 of all CT lay in a 100–300 μm band just below the retinal dense band, within the deep superficial gray. The two sets of terminals were also partly segregated in the rostral-caudal plane. The rostral tip of the colliculus, which has a representation of the ipsilateral hemifield, had a very dense accumulation of RT, but almost no CT. The area centralis representation, just behind the rostral pole, showed a marked decrease in RT density. CT were most densely distributed in this region. In more caudal regions of the colliculus, RT gradually increased while CT decreased in density. The medial to lateral distribution of both RT and CT had obvious peaks and troughs, but these were randomly distributed. These results indicate that: (1) RT and CT synapses in the colliculus overlap less than previously reported. It is, therefore, likely that many cells in the superior colliculus do not receive afferents from both sources. (2) Although retinal and cortical terminals have a patchy distribution, there is no indication that they form regular, alternating columns in the superior colliculus.

Prenatal formation of cortical input and development of cytoarchitectonic compartments in the neostriatum of the rhesus monkey

The timing, hemispheric laterality, and mode of termination of input from the prefrontal association cortex to the neostriatum were studied in fetal and neonatal rhesus monkeys using autoradiography for tracing connections. In addition, the cytological maturation of the neostriatum was examined in Nissl-stained sections from the same and other monkeys of selected prenatal and postnatal ages. A small contingent of corticostriatal axons reaches both the caudate nucleus and the putamen by the 69th embryonic day (E69) of the 165-day gestation period in this species and steadily expands over the next 3 fetal months. Throughout this period, ipsilateral perfrontostriatal connections predominate, and only a small and variable amount of label is detectable over the contralateral neostriatum. A major feature of the developing corticostriatal projection is a transfiguration in the distribution of its terminals: from E69 to E95, cortical terminals are distributed uniformly among neostriatal neurons; beginning around E105, areas of higher and lower grain density begin to emerge until finally, by E133, 250- to 500-micrometers-wide circular and elliptically shaped label-free cores perforate a field of densely labeled cortical terminals as in the neostriatum of the adult monkey (Goldman, P. S., and W. J. H. Nauta (1977) J. Comp. Neurol. 171: 369-386). The cytoarchitectonic composition of the neostriatum also changes during gestation: from E69 through E95, the small postmitotic neurons of the immature neostriatum are packed densely and, for the most part, are distributed homogeneously; by E105, they become segregated into cellular islands consisting of densely packed neurons that are encapsulated by fiber-rich annuli and embedded in a matrix of less densely arrayed neurons. The shape and size of the islands in Nissl-stained sections correspond to label-free cores in autoradiograms of fetuses with cortical injections, while the surrounding annuli and adjacent matrix cells correspond to areas of dense accumulation of label. Thus, the formation of the corticostriatal projection in primates involves a transformation in the distribution of ingrowing terminals synchronized with changes in cellular organization of the neostriatum.

5-HT concentration in cat's brain

Endogenous concentrations of TRP, 5-HT and 5-HIAA were determined in the different cortical and subcortical areas of adult cat's brain, using ion-exchange chromatography and spectrofluorimetric methods. Tryptophan is homogeneously distributed in all structures of the brain. 5-HT is mainly accumulated in the brain stem, hypothalamus and caudate nucleus, but also in cortical areas as olfactory and piriform gyrus. The ratio 5-HIAA/5-HT shows that 5-HT utilization is higher in the structures containing small amounts of 5-HT. Using the radioenzymatic assay described by Saavedra et al. (1973), the rostrocaudal distribution of 5-HT content was determined in olfactory and piriform cortex. Important concentrations of 5-HT were detected in the prepiriformis and anterior amygdaloidea areas. Using the same assay and microdissection on frozen frontal slices of the brain, the distribution of 5-HT concentration throughout the different layers of cortical areas was studied. Piriform, olfactory and sigmoid cortex present high concentrations in the superficial layers, including the molecular one. These results were confirmed by uptake studies, made on crude homogenates from frozen tissue, suggesting that 5-HT is mainly contained in the most external cortical terminals.

The ventral lateral geniculate nucleus, pars lateralis of the rat. Synaptic organization and conditions for axonal sprouting.

The synaptic organization of the pars lateralis portion of the ventral lateral geniculate nucleus is similar to that of other thalamic nuclei. There are four types of synaptic knobs (RL, RS, F1, F2). RL knobs are large and irregularly shaped, contain round synaptic vesicles and make multiple asymmetrical junctions. They are found primarily in "synaptic islands" making contact with gemmules, spines, small dendrites, and other synaptic profiles containing pleiomorphic synaptic vesicles (F2). Smaller RS knobs contain round vesicles and make asymmetrical junctions with the same type of elements as RL knobs, with the exception of the F2 profiles, but are seldom found in synaptic islands. F1 knobs contain flattened synaptic vesicles and form symmetrical junctions with F2 knobs, gemmules, spines, and small-medium dendrites in synaptic islands, throughout the neuropil, and on the proximal dendrites and soma of the largest type of neuron. F2 knobs are irregularly shaped, contain pleiomorphic synaptic vesicles and make symmetrical junctions primarily with gemmules and spines in synaptic islands. They are postsynaptic to RL and F1 knobs. Occipital decortication indicates that cortical terminals are of the RS type. Bilateral enucleation indicates that retinal terminals are of both the FL and RS type. The large amount of geographic overlap of retinal and cortical terminals on gemmules, spines, and small dendrites found in the neuropil outside of synaptic islands logically would maximize axonal sprouting between these two sources.

Histochemical demonstration of transmitter release from noradrenaline, dopamine and 5-hydroxytryptamine nerve terminals in field stimulated rat brain slices.

The effect of electrical field stimulation on noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) nerve terminals in rat brain slicesin vitro was investigated. Slices prepared from the cerebral cortex or the neostriatum were incubated in physiologic buffer for 30 min and then superfused by buffer and stimulated by an electrical field (biphasic pulses, 10 Hz, 12 mA, 2 ms) for various time periods. The effect of the stimulation was studied at the cellular level with the histochemical fluorescence technique of Falck and Hillarp. The transmitter overflow into the superfusing buffer caused by the stimulation was studied with isotope technique. Cerebral Cortex NA Nerve Terminals. Stimulation caused release of NA from cortical NA nerve terminals. Already after 2 min stimulation a slight decrease of the fluorescence intensity of the nerve terminals could be found. Stimulation for 15 to 30 min greatly reduced the fluorescence intensity. In slices preincubated with3H-NA the stimulation-induced overflow of tritium during 2 min stimulation was about 15% (i.e. 15% of the tissue tritium content was overflowing into the superfusing buffer in response to stimulation for 2 min). During prolonged stimulation there was a considerable decline of the tritium efflux. Cerebral Cortex 5-HT Nerve Terminals. The 5-HT-analogue 6-hydroxytryptamine (6-HT) which is readily taken up into 5-HT nerve terminals was used to permit good visualization of these nerve terminals. Uptake of 6-HT into cortical NA nerve terminals was prevented by preincubation with 6-hydroxydopamine (6-OH-DA) or protriptyline. Stimulation for 15 to 30 min reduced the fluorescence intensity of the 5-HT nerve terminals. In slices preincubated with3H-5-HT the stimulation-induced overflow of tritium during 2 min stimulation was about 5%. The tritium efflux slowly decreased during continuous stimulation. Neostriatal DA Nerve Terminals. In slices frozen directly after preparation an intense diffuse fluorescence could be seen. After incubation in drug-free buffer at 37° C the fluorescence was localized in the varicosities of the DA nerve terminals. The central parts of the slices almost completely lacked specific fluorescence, while the outer zones were brightly fluorescent. No clear reduction of the fluorescence intensity of the DA nerve terminals in the outer zone could be observed after stimulation for 30 min. In slices preincubated with3H-DA the stimulation-induced overflow of tritium during 2 min stimulation was about 2%. The tritium efflux slowly decreased during continuous stimulation. It is suggested that the differences in release between the various nerve terminal systems foundin vitro reflect differences in transmitter release occurringin vivo. The comparably high release of NA per impulse from the cortical NA nerve terminals implicate that the discharge rate of these neuronsin vivo is very low.

Receptive fields and synaptic organization of the superficial gray layer of the cat superior colliculus

Cells in the superficial gray layer of the cat superior colliculus show binocular interaction and respond selectively to certain features of a visual stimulus, for example, movement, direction, and size. Although the binocular and directional properties depend on input from the visual cortex, certain spatial properties of the receptive field do not. Neither can they depend exclusively on the retino-collicular input since this is mainly from the contralateral eye. Therefore, the spatial properties must arise from an intrinsic collicular mechanism that can be activated from either eye. Seen with the electron microscope the most striking feature of the synaptic organization is that the dendrites make extensive synaptic contacts with each other. Synapses from the retina and visual cortex terminate on the vesicle-free regions of the dendrites and also on the regions given rise to dendro-dendritic contacts. Retinal and cortical terminals are rare on cell bodies, and neither type makes, nor appears to receive an axo-axonic contact. If the dendro-dendritic contacts are inhibitory, they may represent the basis on which complicated receptive field properties are established in the colliculus using only limited number of cells.