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Selective lesions of neural pathways following viral inoculation of the olfactory bulb.

In the present study, herpes simplex virus type 1 (HSV1) was injected into the olfactory bulb of the rat in order to determine the impact of viral infection on neural pathways, neurotransmitters, and behavior. In many animals, these injections caused considerable neuronal loss in regions that project to the bulb including the primary olfactory cortex and locus coeruleus (LC). Short-term (2-5 days postinjection) studies using immunocytochemical colocalization of virus and transmitter markers showed that cholinergic (ACh) neurons in the horizontal nucleus of the diagonal band, serotonergic (5-HT) neurons in the dorsal and median raphe nuclei, and noradrenergic (NE) neurons in the LC became infected with virus. Almost all NE neurons in the ipsilateral LC were infected while a smaller proportion of 5-HT and ACh neurons in their respective nuclei contained virus. In order to determine long-term effects of viral infection, virus injection into the olfactory bulb was followed by antiviral treatment and sacrifice 17 days to 7 months postinjection. Quantitative analysis of selected cortical regions (olfactory bulb, cingulate cortex, parietal cortex) revealed decreased NE-immunoreactive fibers while 5-HT axons from the dorsal and median raphe nuclei were not significantly affected. No changes in acetylcholinesterase staining in these cortical regions were observed, indicating that cholinergic axons were not significantly changed. Ten of the 36 animals that survived long-term after HSV1 inoculation were also tested in a water maze task before sacrifice to determine if the viral infection was associated with spatial learning deficits. Spatial learning deficits correlated with the degree of primary olfactory cortex damage but not with 5-HT, NE, or ACh axon losses.

Animals↗

Mitral cell-to-glomerulus connectivity: an HRP study of the orientation of mitral cell apical dendrites.

It has been suggested that the principal output cells of the main olfactory bulb, the mitral cells, along with the glomerulus they enter, form an anatomical and functional column. To test the extent to which mitral cell somata lying close together in the mitral cell layer are connected to the same glomerulus, we reconstructed 267 mitral cells labeled by extracellular injections of horseradish peroxidase (HRP) in the external plexiform layer. Results show that apical dendrites tilt rostrally from the somata to the glomeruli and this tilt is gradually greater as the somata are located more and more rostrally in the olfactory bulb. The apical dendrites of most mitral cells in the same region of the bulb are parallel. We analyzed the degree to which dendrites were parallel by measuring the difference in angle of all pairs of apical dendrites in each section, with the restriction that no cells were separated by more than 500 microns. About half of these pairs of dendrites differed in angle by 20 degrees or less and were therefore said to be parallel. The degree of parallelism did not vary with the cell pair location or with intercell distance. Study of glomerular connections of pairs of mitral cells as a function of intercell distance revealed that 96% of mitral cells connected to the same glomerulus were separated by less than 120 microns, while 72% of cells connected to adjacent glomeruli and only 29% of cells connected to distant, i.e., nonadjacent, glomeruli were separated by less than 120 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antennal lobe projection patterns of olfactory receptor neurons involved in sex pheromone detection in Spodoptera littoralis (Lepidoptera: Noctuidae).

Pheromone-specific receptor neurons in male and female cotton leafworms, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) were typed physiologically and traced into the antennal lobe using cobalt lysine as a marker. In male S. littoralis, the macroglomerular complex (MGC), which is responsible for the initial integration of information concerning sex pheromone components, contains three glomerular compartments as revealed in a morphological study. No such specialized structure was seen in the female. In the male, olfactory receptor neurons that responded selectively to stimulation with the major sex pheromone component, (Z)9, (E)11-tetradecadienyl acetate (Z9E11-14:OAc), had arborizations that were restricted to a large glomerulus of the MGC (designated a), situated near the antennal nerve entrance into the antennal lobe. Neurons that were stimulated by (Z)9,(E)12-tetradecadienyl acetate (Z9E12-14:OAc), a second pheromone component, had arborizations in a lateral, smaller glomerulus of the MGC (designated c), while receptor neurons specifically tuned to a behavioural antagonist, (Z)-9-tetradecenol (Z9-14:OH), projected to a medial glomerulus of the MGC (b). In the female, receptor neurons tuned to the major pheromone component projected to a glomerulus situated at the entrance of the antennal nerve. This glomerulus did, however, not have the size or the structure of the male MGC. A second neuron housed in the same sensillum projected its axon to an ordinary glomerulus situated medially in the antennal lobe.

Animals↗

Connectivity and cytoarchitecture of the ventral telencephalon in the salamander Plethodon shermani.

The cytoarchitecture and axonal connection pattern of centers in the ventral telencephalon of the salamander Plethodon shermani were studied using biocytin for anterograde and retrograde labeling of cell groups, as well as by intracellular injections. Application of biocytin to the main and accessory olfactory bulbs identified the olfactory pallial regions and the vomeronasal portion of the amygdala, respectively. According to our results, the amygdala of Plethodon is divided into (1) a rostral part projecting to visceral and limbic centers and receiving afferents from the dorsal thalamus, and (2) a caudal part receiving accessory olfactory input. The striatopallial transition area (SPTA) lies rostrodorsally to the caudal (vomeronasal) amygdala and is similar in connections and possibly in function. The rostral striatum has few descending projections to the medulla, whereas the intermediate striatum sends strong projections to the tegmentum and medulla. The caudal striatum has strong ascending projections to the striatum and descending projections to the ventral hypothalamus. The dendritic trees of neurons labeled below the striatum and in the SPTA spread laterally from the soma, whereas dendrites of striatal neurons converge into the laterally situated striatal neuropil. In the caudal amygdala, three distinct types of neurons are found differing in dendritic arborization. It is concluded that, hodologically, the rostral part of the urodele amygdala corresponds to the central and basolateral amygdala and the caudal part to the cortical/medial amygdala of mammals. The urodele striatum is divided into a rostral striatum proper, an intermediate dorsal pallidum, and a caudal part, with distinct connections described here for the first time in a vertebrate.

Animals↗

Activity-dependent changes in synaptophysin immunoreactivity in hippocampus, piriform cortex, and entorhinal cortex of the rat.

Synaptophysin, an integral membrane glycoprotein of synaptic vesicles, has been widely used to investigate synaptogenesis in both animal models and human patients. Kindling is an experimental model of complex partial seizures with secondary generalization, and a useful model for studying activation-induced neural growth in adult systems. Many studies using Timm staining have shown that kindling promotes sprouting in the mossy fiber pathway of the dentate gyrus. In the present study, we used synaptophysin immunohistochemistry to demonstrate activation-induced neural sprouting in non-mossy fiber cortical pathways in the adult rat. We found a significant kindling-induced increase in synaptophysin immunoreactivity in the stratum radiatum of CA1 and stratum lucidum/radiatum of CA3, the hilus, the inner molecular layer of the dentate gyrus, and layer II/III of the piriform cortex, but no significant change in layer II/III of the entorhinal cortex, 4 weeks after the last kindling stimulation. We also found that synaptophysin immunoreactivity was lowest in CA3 near the hilus and increased with increasing distance from the hilus, a reverse pattern to that seen with Timm stains in stratum oriens following kindling. Furthermore, synaptophysin immunoreactivity was lowest in dorsal and greatest in ventral sections of both CA3 and dentate gyrus in both kindled and non-kindled animals. This demonstrates that different populations of sprouting axons are labeled by these two techniques, and suggests that activation-induced sprouting extends well beyond the hippocampal mossy fiber system.

Animals↗

Effects of estrogen treatment on sensorimotor task performance and brain dopamine concentrations in gonadectomized male and female CD-1 mice.

In Experiment I, castrated male and female CD-1 mice +/- estradiol benzoate (EB) treatment were tested for their performance on a skilled sensorimotor task consisting of walking across beams of varying widths (6, 9, 12, and 21 mm). To evaluate whether behavioral performance was related to nigrostriatal dopaminergic function, tissue dopamine concentrations were determined from the corpus striatum as well as the hypothalamus and olfactory tubercle. In general, sensorimotor performance improved for all treatment conditions as the beam width increased. Castrated male mice treated with oil vehicle showed the worst performance as indicated by significantly greater amounts of time to cross the beam. Treatment of castrated males with EB significantly improved their performance. Performance of the castrated females was not changed by EB treatment and was similar to that observed with the castrated + EB males. Significant gender differences in dopamine concentrations (female > male) were obtained in the corpus striatum, as well as the olfactory tubercle and hypothalamus. Dopamine levels were unaltered by EB treatment. In Experiment II, behavioral and neurochemical determinations were directly compared between castrated and intact male mice. Behavioral performance of castrates was significantly reduced compared to intact males. No differences in dopamine concentrations were obtained between these two groups; however, the hypothalamic dopamine/DOPAC ratio of castrates was significantly greater than that of intact male mice. These results demonstrate significant modulatory effects of EB in castrated male, but not female, mice upon sensorimotor performance and indicate that this task may provide an effective means to partial out modulatory effects of gonadal steroid hormones upon skilled sensorimotor performance. When the data of Experiments I and II are combined, it appears that the basis of this sensorimotor deficit in the males is the absence of gonadal steroid hormones. In addition, these results reveal significant gender differences in various dopaminergic systems in these mice.

3,4-Dihydroxyphenylacetic Acid↗

Lesions of the accessory olfactory bulb decrease lordotic responsiveness and reduce mating-induced c-fos expression in the accessory olfactory system.

The effect of bilateral lesion of the accessory olfactory bulb (AOB) on the mating-induced enhancement of sexual receptivity was investigated in ovariectomized (OVX) female rats. Lesions of the AOB significantly reduced the lordosis-to-mount (L/M) ratio in mating tests conducted 20 to 50 days after the lesion but L/M ratios at earlier (10 days) and later (51-90 days) time periods were not affected. The decrease in L/M was accompanied by a reduction in the number of c-fos immunopositive cells in the medial amygdala (mAMYG) and bed nucleus of the stria terminalis (BNST) measured after 3 h of repetitive mating. In the mAMYG, the reduction in c-fos immunoreactivity was correlated to the L/M ratio as well as to the number of intromissions received during the mating tests. The results suggest that information processed from the AOB to the mAMYG and the BNST is important for facilitation of lordosis behavior, and that the mAMYG may integrate information from the AOB with ascending input activated during copulatory behavior to regulate receptivity.

Amygdala↗

Retrograde axonal transport following injection of [3H]serotonin in the olfactory bulb. I. Biochemical study.

A retrograde axonal transport from the serotonergic nerve terminals in the olfactory bulb (OB) to their parent cell bodies in the midbrain raphe nuclei has been demonstrated after stereotaxic injection of [2H]5-HT into the OB of rats pretreated with a monoamine oxidase (MAO) inhibitor: at various time intervals thereafter (4-92 h) there was a preferential accumulation of radioactivity mainly in the raphe dorsalis nucleus (RDN). Maximal accumulation occurred at 24 h. Of this radioactivity, 30-50% was recovered as 5-HT. The accumulation was estimated to take place at two rates: a fast one (48 mm/day) and a slower one (16 mm/day). Under the same experimental conditions there was no clear evidence for a retrograde accumulation of [3H]norepinephrine in the RDN. A passive diffusion mechanism could be excluded since the diffuson of tracer towards the cerebrospinal fluid was prevented by prior mechanical obstruction of the olfactory diverticle of the lateral ventricle. Furthermore, colchicine strongly reduced (by 80%) the radioactive accumulatin in the RDN. Destruction of serotonergic nerve terminals by 5,6-dihydroxytryptamine or inhibiton of 5-HT uptake by fluoxetine decreased this retrograde accumulation whereas destruction of catecholaminergic nerve terminals by 6-hydroxydopamine was without effect. Pretreatment with reserpine decreased the amount of radioactivity transported to the RDN by 40%. In the absence of MAO inhibition pretreatment, animals still presentd 35% of the tracer transported to the RDN. Intrabulbar injection of MAO inhibitor did not affect the accumulation rates when compared with animals which received the inhibitor by the intraperitoneal route. In conclusion, the retrograde axonal transport following [3H]5-HT injection in the serotonergic RDN-OB system occurs via an active process which depends on a colchicine-sensitive mechanism and is partially linked to a reserp ine-sensitive structure. During its transport, the amine seems to be relatively protected from metabolic inactivation.

Animals↗

An experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). I: Olfactory bulb and ventral area.

The fluorescent carbocyanine dye 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to comprehensively analyze the connections of the olfactory bulbs and the different regions of the ventral (V) area of the telencephalic lobes (subpallium) of the rainbow trout. With this goal, DiI was applied to the different telencephalic nuclei and zones, as well as to the olfactory nerve, the olfactory bulb, the retina, and to several structures in the diencephalon and brainstem of juvenile trout. The olfactory bulbs maintain reciprocal connections with several regions of the telencephalon [ventral nucleus of V (Vv), supracommissural nucleus (Vs), posterior zone of D (Dp), preoptic nucleus], and also project to the diencephalon (posterior tuberal nucleus, posterior hypothalamic lobe). Vv receives afferents from Vs, the dorsal nucleus of V (Vd), the preoptic nucleus, and from several nuclei in the diencephalon and brainstem (suprachiasmatic nucleus, anterior and lateral tuberal nuclei, preglomerular complex, tertiary gustatory nucleus, posterior tubercle, inferior hypothalamic lobes, thalamus, torus semicircularis, secondary gustatory nucleus, locus coeruleus, superior raphe nucleus, central gray, and reticular formation), and projects to dorsal (pallial) regions and most of the nuclei afferent to Vv. The dorsal nucleus of V (Vd) and Vs mainly project to the dorsal area. In an accompanying article (Folgueira et al., 2004), we present the results of application of DiI to dorsal (pallial) telencephalic regions, as well as of several experiments of tracer application to extratelencephalic regions. The results presented here, together with those of the accompanying article, reveal a complex connectional pattern of the rainbow trout ventral telencephalon, most of these connections having not been described previously in salmonids.

Animals↗

Alcohol-preferring rats: genetic sensitivity to alcohol-induced stimulation of dopamine metabolism.

The effect of ethanol on brain dopamine (DA) metabolism in the caudate nucleus (CN), olfactory tubercle (OT) and medial prefrontal cortex (MPFC) was compared in two selectively bred rat lines, one ethanol preferring and the other ethanol nonpreferring. Male rats from the 16th and 17th generations of both lines that never experienced ethanol beforehand were used. No differences in the basal concentrations of DA and its metabolites, DOPAC and HVA, in the above brain regions were found between the two lines. The oral administration of 2 g/kg of ethanol to ethanolnonpreferring rats increased DOPAC and HVA and reduced DA levels in the CN and OT but was ineffective in the MPFC. On the other hand, ethanol administration to ethanol-preferring rats decreased DA content and increased DOPAC and HVA levels, not only in the CN and OT, but also in the MPFC. Moreover, the changes induced by ethanol on DA metabolism in the latter group were significantly greater than in ethanol nonpreferring rats. These results indicate that ethanol preferring rats have a genetic high sensitivity to the ethanol effect on DA metabolism, and suggest that such a trait might play a role in ethanol preference.

3,4-Dihydroxyphenylacetic Acid↗

Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation.

Expression of the homeodomain-containing transcription factors Dlx-1 and Dlx-2 in the lateral (LGE) and medial (MGE) ganglionic eminences, subpallial embryonic structures, is required for generation of telencephalic interneurons. LGE- and MGE-derived progenitors migrate and populate a number of forebrain structures, including the cortex, hippocampus, and olfactory bulb (OB). Previous reports focusing on embryogenesis of telencephalic neurons in Dlx-1 and Dlx-2 null mice suggested a specific role for these genes in expression of the OB dopamine (DA) phenotype. We have investigated whether these genes also are expressed in adult brain, especially in those pallial derivatives, such as the OB, hippocampus, and possibly cortex, where neurogenesis continues in adults. With a highly sensitive, nonradioactive in situ hybridization technique and both DLX-2 and pan DLX antisera, widespread expression of both genes was found in adult mouse fore- but not mid- or hindbrain. The adult unilateral naris closure paradigm was employed to establish a causative role for Dlx in regulating tyrosine hydroxylase (TH) expression; TH is the first enzyme in DA biosynthesis. TH mRNA, but not Dlx expression, was significantly down-regulated in the OB ipsilateral to closure. These findings suggest that Dlx-1 and -2 do not play a direct role in DA phenotypic differentiation and TH gene regulation in adult OB. The widespread expression of Dlx mRNA and protein in the adult brain suggests that these genes may have additional roles in mature animals.

Animals↗

Cholinergic systems in the rat brain: I. projections to the limbic telencephalon.

The cholinergic projections to the limbic telecephalon in the rat were investigated by use of fluorescent tracer histology in combination with choline-O-acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) histochemistry (pharmacohistochemical regimen). Propidium iodide or Evans Blue was infused into the olfactory bulb, hippocampus, dorsal retrohippocampal region, amygdala, and the entorhinal, perirhinal, pyriform, insular, and cingular cortices. Retrogradely transported fluorescent labels and ChAT and/or AChE were microscopically analyzed on the same brain section. Virtually all of the cholinergic projections to the limbic telencephalon derived from the basal forebrain cholinergic system composed of neurons associated with the medial septal nucleus, nuclei of the vertical and horizontal limbs of the diagonal band, the magnocellular preoptic area, the subpallidal substantia innominata and its rostral extension into the regions of the ventral pallidum laterally and the lateral preoptic area medially, and the nucleus basalis. The cingulate cortex received a small cholinergic projection from the dorsolateral tegmental nucleus in the brainstem. All of the presumed cholinergic innervation of the olfactory bulb, hippocampus, and dorsal retrohippocampal area and the majority of cholinergic afferents to posterior cingulate and entorhinal cortices derived from the medial septal nucleus, vertical and horizontal limbs of the diagonal band, magnocellular preoptic area, and rostral substantia innominata. Putative cholinergic afferents to the amygdala and to pyriform, insular, perirhinal, and anterior cingulate cortices orginated from ChAT-positive cells concentrated more caudally in the basal forebrain cholinergic system. Within the basal forebrain, no simple topographic pattern emerged to explain the cholinergic innervation of the limbic telencephalon, although an essentially reverse rostrocaudal organization was observed for afferents to the cingular region. It was noted, however, that most regions of the limbic telencephalon received cholinergic input from rostral portions of the basal forebrain cholinergic system, an observation inviting speculation that anterior aspects of the basal forebrain provide cholinergic afferents primarily to limbic structures in the telencephalon whereas more caudal portions are the source of cholinergic fibers preferentially innervating non-limbic regions. Of the total number of projection neurons innervating a given region of the limbic telencephalon, a greater proportion was ChAT-positive if phylogenetically newer target structures were innervated.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

Olfactory bulb networks revealed by lateral olfactory tract stimulation in the in vitro isolated guinea-pig brain.

Olfactory information processing is mediated by synaptic connections between the olfactory bulbs (OBs) and piriform-limbic cortices. Limited accessibility using common in vivo and in vitro preparations has hindered previous attempts to define these synaptic interactions. We utilized the isolated guinea-pig brain preparation to overcome these experimental limitations. Previous studies demonstrated extensive functional preservation in this preparation maintained in vitro by arterial perfusion. Field potential laminar profiles were performed with multi-channel probes in the OB following stimulation of both the lateral olfactory tract (LOT) and the anterior piriform cortex (APC). Current-source density analysis was carried out on laminar profiles to reconstruct current sinks/sources associated with intrinsic synaptic activities. LOT stimulation induced sequentially i) an antidromic population spike (at 2.66+/-0.39 ms) located in the mitral cell layer that was resistant to 100 Hz high-frequency stimulation (HFS) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM), ii) a component located in the external plexiform layer at 3.85+/-0.63 ms that was unaffected by HFS, iii) a large amplitude potential (peak amplitude at 5.84+/-0.58 ms) generated in the external plexiform layer, abolished by HFS and CNQX, but not by bicuculline (50 microM), iv) a late response (onset at 20.00+/-2.94 ms) abolished by CNQX and enhanced by bicuculline. Stimulation of the APC also induced a late potential abolished by HFS and CNQX. Both APC-evoked and late LOT-evoked responses were abolished by a transverse cut to separate OB from APC. These results demonstrate in an isolated mammalian brain preparation the presence of reciprocal synaptic interactions between the OB and piriform cortical structures.

2-Amino-5-phosphonovalerate↗

Cluster organization and response characteristics of the giant fiber pathway of the blowfly Calliphora erythrocephala.

Intersegmental descending neurons (DNs) link the insect brain to the thoracic ganglia. Iontophoresis of cobalt or fluorescent dyes reveals DNs as uniquely identifiable elements, the dendrites of which are situated within a characteristic region of the lateral deutocerebrum. Here we demonstrate that DNs occur as discrete groups of elements termed DN clusters (DNCs). A DNC is a characteristic combination of neurons that arises from a multiglomerular complex in which the main components of each glomerulus are a characteristic ensemble of sensory afferents. Other neurons involved in the complex are local interneurons, heterolateral interneurons that connect DNCs on both sides of the brain, and neurons originating in higher centers of the brain. We describe the structure, relationships, and projections of eight DNs that contribute to a descending neuron cluster located ventrally in the lateral deutocerebrum, an area interposed between the ventral antennal lobes and the laterally disposed optic lobes. We have named this cluster the GDNC because its most prominent member is the giant descending neuron (GDN), which plays a cardinal role in the midleg "jump" response and which is implicated in the initiation of flight. The GDN and its companion neurons receive primary mechanosensory afferents from the antennae, terminals of wide- and small-field retinotopic neurons originating in the lobula, and endings derived from sensory interneurons that originate in leg neuropil of the thoracic ganglia. We demonstrate that DNs of this cluster share morphological and functional properties. They have similar axon trajectories into the thoracic ganglia, where they invade functionally related neuropils. Neurons of the GDNC respond to identical stimulus paradigms and share similar electrophysiological characteristics. Neither the GDN nor other members of its cluster show spontaneous activity. These neurons are reluctant to respond to unimodal stimuli, but respond to specific combinations of visual and mechanosensory stimulation. These results suggest that in flies groups of morphologically similar DNs responding to context-specific environmental cues may cooperate in motor control.

Action Potentials↗

Neural system-enriched gene expression: relationship to biological pathways and neurological diseases.

To understand the commitment of the genome to nervous system differentiation and function, we sought to compare nervous system gene expression to that of a wide variety of other tissues by gene expression database construction and mining. Gene expression profiles of 10 different adult nervous tissues were compared with that of 72 other tissues. Using ANOVA, we identified 1,361 genes whose expression was higher in the nervous system than other organs and, separately, 600 genes whose expression was at least threefold higher in one or more regions of the nervous system compared with their median expression across all organs. Of the 600 genes, 381 overlapped with the 1,361-gene list. Limited in situ gene expression analysis confirmed that identified genes did represent nervous system-enriched gene expression, and we therefore sought to evaluate the validity and significance of these top-ranked nervous system genes using known gene literature and gene ontology categorization criteria. Diverse functional categories were present in the 381 genes, including genes involved in intracellular signaling, cytoskeleton structure and function, enzymes, RNA metabolism and transcription, membrane proteins, as well as cell differentiation, death, proliferation, and division. We searched existing public sites and identified 110 known genes related to mental retardation, neurological disease, and neurodegeneration. Twenty-one of the 381 genes were within the 110-gene list, compared with a random expectation of 5. This suggests that the 381 genes provide a candidate set for further analyses in neurological and psychiatric disease studies and that as a field, we are as yet, far from a large-scale understanding of the genes that are critical for nervous system structure and function. Together, our data indicate the power of profiling an individual biologic system in a multisystem context to gain insight into the genomic basis of its structure and function.

Animals↗

Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes.

There is evidence for lymphatic drainage of interstitial fluid from the brain along perivascular spaces in a number of mammalian species. Ultrastructural studies suggest that there are similar drainage pathways in the human cerebral cortex. Perivascular spaces in the basal ganglia, however, differ from those in the cortex in that they dilate to form lacunes and rarely accumulate beta-amyloid (amyloid angiopathy) in Alzheimer's disease; in the cortex, lacunes are rare but amyloid angiopathy is common. The aim of the present study is to compare the structure of perivascular spaces in the basal ganglia and at the anterior perforated substance with perivascular spaces in the cerebral cortex. Eight postmortem brains from patients aged 23-80 years (mean 68 y) were examined by light microscopy, by scanning and transmission electron microscopy and by direct visualisation of etched paraffin blocks. The results show that arteries in the basal ganglia are surrounded by 2 distinct coats of leptomeninges separated by a perivascular space which is continuous with the perivascular space around arteries in the subarachnoid space. The inner layer of leptomeninges closely invests the adventitia of the vessel wall and the outer layer is continuous with the pia mater on the surface of the brain at the anterior perforated substance. Veins in the basal ganglia have no outer layer of leptomeninges and thus the perivascular space is continuous with the subpial space. The anatomy of the periarterial spaces in the basal ganglia differs significantly from that in the cerebral cortex where there is only a single periarterial layer of leptomeninges. Differences in structure of perivascular spaces around arteries may reflect relative efficiencies in the drainage of interstitial fluid from different sites in the brain. Furthermore, the structure of the perivascular spaces may contribute to the relatively high frequency of lacunes in the basal ganglia, and the low frequency of amyloid angiopathy at this site in Alzheimer's disease.

Adult↗

Metabotropic glutamate receptors in the main olfactory bulb drive granule cell-mediated inhibition.

Main olfactory bulb (MOB) granule cells (GCs) express high levels of the group I metabotropic glutamate receptor (mGluR), mGluR5. We investigated the role of mGluRs in regulating GC activity in rodent MOB slices using whole cell patch-clamp electrophysiology. The group I/II mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD) or the selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) depolarized ( approximately 20 mV) and increased the firing rate of GCs. In the presence of ionotropic glutamate and GABA receptor antagonists, DHPG evoked a more modest depolarization ( approximately 8 mV). In voltage clamp, DHPG, but not group II [(2S,2'R,3)-2-(2',3'-dicarboxycyclopropyl)glycine, DCG-IV] or group III [L(+)-2-amino-4-phosphonobutyric acid, L-AP4] mGluR agonists, induced an inward current. The inward current reversed polarity near the potassium equilibrium potential, suggesting mediation by closure of potassium channels. The DHPG-evoked inward current was unaffected by the mGluR1 antagonist (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), was blocked by the group I/II mGluR antagonist (alphaS)-alpha-amino-alpha-[(1S,2S)-2-carboxycyclopropyl]-9H-xanthine-9-propanoic acid (LY341495), and was absent in GCs from mGluR5 knockout mice. LY341495 also attenuated mitral cell-evoked voltage-sensitive dye signals in the external plexiform layer and mitral cell-evoked spikes in GCs. These results suggest that activation of mGluR5 increases GC excitability, an effect that should increase GC-mediated GABAergic inhibition of mitral cells. In support of this: DHPG increased the frequency of spontaneous GABAergic inhibitory postsynaptic currents in mitral cells and LY341495 attenuated the feedback GABAergic postsynaptic potential elicited by intracellular depolarization of mitral cells. Our results suggest that activation of mGluR5 participates in feedforward and/or feedback inhibition at mitral cell to GC dendrodendritic synapses, possibly to modulate lateral inhibition and contrast in the MOB.

Action Potentials↗

Extrinsic and intrinsic fiber connections of the telencephalon in a teleost, Sebastiscus marmoratus.

Extrinsic and intrinsic fiber connections of the telencephalic subdivisions of Nieuwenhuys ('62) in a teleost, Sebastiscus marmoratus, were studied by means of horseradish peroxidase (HRP) and Fink-Heimer methods. The olfactory bulb projects bilaterally to area dorsalis pars posterior, area ventralis pars ventralis, pars lateralis, pars posterior, pars intermedia, and the nucleus posterior tuberis of Peter et al. ('75) and receives fibers from ipsilateral area dorsalis pars centralis, pars posterior, area ventralis pars dorsalis, and pars supracommissuralis. Area dorsalis pars posterior sends numerous fibers to the ipsilateral ventral region of area dorsalis pars medialis, from which fibers of the medial forebrain bundle arise and terminate in the inferior lobe and nucleus posterior tuberis. Area dorsalis pars lateralis, pars dorsalis, and the dorsal region of pars medialis are the main targets of extratelencephalic ascending afferents. Area dorsalis pars lateralis receives fibers from the ipsilateral nucleus prethalamicus of Meader ('34), where tectal projections terminate massively. Area dorsalis pars dorsalis and the dorsal region of pars medialis receive afferents from the ipsilateral nucleus preglomerulosus of Schnitzlein ('62), nucleus posterior tuberis, area preoptica pars medialis of Crosby and Showers ('69), and nucleus entopeduncularis of Sheldon ('12). Raphe nuclei and locus ceruleus project bilaterally to area dorsalis pars centralis, pars dorsalis, pars lateralis, and the dorsal region of pars medialis. Area dorsalis pars centralis, pars dorsalis, and the dorsal region of pars medialis are important sources of extratelencephalic efferents. These subdivisions give rise to the lateral forebrain bundle and project to the ipsilateral nucleus prethalamicus, nucleus preglomerulosus, inferior lobe, nucleus paracommissuralis of Ito et al. ('82), optic tectum, torus semicircularis, and the bilateral mesencephalic tegmentum. Within the telencephalon, most of the ventral subdivisions project to ipsilateral area dorsalis pars centralis, pars dorsalis, pars lateralis, and the dorsal region of pars medialis. Area dorsalis pars centralis has reciprocal connections with ipsilateral area dorsalis pars lateralis, pars dorsalis, pars posterior, and the dorsal region of pars medialis. A dorsal part of the anterior commissure is composed of axons of the ventral region of area dorsalis pars medialis destined to the contralateral ventral region of area dorsalis pars medialis. A ventral part of the anterior commissure contains axons of area dorsalis pars centralis destined to contralateral area dorsalis pars lateralis.

Animals↗