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S Oleskevich

Publications and source records attributed to S Oleskevich.

At least 19 recordsLinked to original sources
PubMed2006

Locating the scala media in the fixed human temporal bone for therapeutic access: a preliminary study.

OBJECTIVE: To investigate the location of the scala media in relation to the round window niche in human temporal bones. DESIGN: Ten human temporal bones were investigated by radical mastoidectomy and promontory drill-out. SETTING: Temporal bone laboratory. OUTCOME MEASURES: The distance from the scala media to the anterior edge of the round window niche, measured by Fisch's stapedectomy measuring cylinders. RESULTS: The scala media was identified at the transection point of a vertical line 1.6 to 2.2 mm (mean=1.8 mm; standard deviation=0.2) anterior to the anterior edge of the round window niche and a horizontal line 0.2 mm inferior to the lower border of the oval window. CONCLUSION: This report demonstrates the point of entry into the scala media via the promontory in fixed temporal bone models, which may provide a site of entry for stem cells and gene therapy insertion.

Cochlear Duct↗
PubMed2005

Development of a robust central auditory synapse in congenital deafness.

Within the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, there is a large central synapse known as the calyx of Held, which mediates high-fidelity glutamatergic transmission. We investigated the effects of congenital deafness on the development of pre- and postsynaptic parameters of synaptic strength at the calyx of Held. Whole cell recordings of evoked excitatory postsynaptic currents (EPSCs) and immunohistochemistry of GluR1-4 subunits were performed using brain stem slices from congenitally deaf or hearing mice at postnatal days P5 and P12. In both hearing and deaf mice there was a similar developmental decrease in the NMDA component of the evoked EPSC. There was a concurrent increase in release probability and number of release sites, contributing to a fivefold increase in evoked AMPA-mediated EPSC amplitude. The increase in release probability is opposite to that found in previous studies at the calyx of Held in the rat. There was also a seven- to eightfold increase in the size of the readily releasable pool of vesicles and a decrease in tetanic depression. The postsynaptic glutamate receptor subunits were similarly developmentally regulated and unaffected by deafness. GluR1 and 4 dominated at both ages. There was a decrease in expression of GluR1-3 from P5 to P12 and a shift from GluR2 to GluR3, indicating that AMPA receptor complexes at P12 are predominantly calcium-permeable. These results demonstrate that early development at this robust synapse proceeds normally with congenital deafness, suggesting that auditory nerve activity does not affect the development of synaptic strength at the calyx of Held.

Animals↗
PubMed2004

Presynaptic plasticity at two giant auditory synapses in normal and deaf mice.

Large calyceal synapses are often regarded as simple relay points, built for high-fidelity and high-frequency synaptic transmission and a minimal requirement for synaptic plasticity, but this view is oversimplified. Calyceal synapses can exhibit surprising activity-dependent developmental plasticity. Here we compare basal synaptic transmission and activity-dependent plasticity at two stereotypical calyceal synapses in the auditory pathway, the endbulb and the calyx of Held. Basal synaptic transmission was more powerful at the calyx than the endbulb synapse: the amplitude of evoked AMPA receptor-mediated excitatory postsynaptic currents (eEPSCs) was significantly greater at the calyx, as were the release probability, and the number of release sites. The quantal amplitude was smaller at the calyx, consistent with the smaller amplitude of spontaneous miniature EPSCs at this synapse. High-frequency trains of stimuli revealed that the calyx had a larger readily releasable pool of vesicles (RRP), less tetanic depression and less asynchronous transmitter release. Activity-dependent synaptic plasticity was assessed in congenitally deaf mutant mice (dn/dn). Previously we showed that a lack of synaptic activity in deaf mice increases synaptic strength at the endbulb of Held via presynaptic mechanisms. In contrast, we have now found that deafness does not affect synaptic transmission at the calyx synapse, as eEPSC and mEPSC amplitude, release probability, number of release sites, size of RRP, tetanic depression and asynchronous release were unchanged compared to normal mice. Synaptic transmission at the calyx synapse is more powerful and has less capacity for developmental plasticity compared to the endbulb synapse.

Animals↗
PubMed2000

Phosphorylation regulates spontaneous and evoked transmitter release at a giant terminal in the rat auditory brainstem.

1. The role of phosphorylation in synaptic transmission was investigated at a large glutamatergic terminal, the endbulb of Held, on bushy cells in the rat anteroventral cochlear nucleus (AVCN). 2. Whole-cell recordings of excitatory postsynaptic currents (EPSCs) were used to examine the effects of kinase inhibitors and activators on low-frequency (baseline) evoked release, spontaneous release, paired-pulse facilitation (PPF) or depression (PPD), repetitive stimuli and recovery from depression. 3. Application of the kinase inhibitor H7 (100 microM) reduced low-frequency evoked EPSC amplitude (by 15 %) and simultaneously increased PPF (or reduced PPD), with no significant change in other aspects of transmission. H7 did not affect the amplitude or frequency of spontaneous miniature EPSCs. 4. Phorbol esters increased EPSC amplitude (by 50 %) with a concomitant decrease in PPF (or increase in PPD), and reduced the final EPSC amplitude during repetitive stimuli. The effect of phorbol esters was due exclusively to protein kinase C (PKC) activation, as the specific PKC inhibitor bis-indolylmaleimide (Bis) completely blocked the potentiating effect of phorbol esters on EPSC amplitude. 5. Significantly, phorbol esters did not increase the evoked EPSC amplitude at connections in which release was maximized using high extracellular calcium concentrations (4-6 mM). 6. Phorbol esters increased the frequency of spontaneous miniature EPSCs in physiological calcium (by 275 %), and in high extracellular calcium (by 210 %) when phorbol esters did not increase the evoked EPSC amplitude. 7. Our results are most consistent with the actions of H7 to decrease low-frequency release probability and phorbol esters to increase low-frequency release probability at the endbulb-bushy cell synaptic connection in the AVCN. The effects of H7 and phorbol esters on paired-pulse responses and tetanic depression appear to be largely consequential to these changes in low-frequency release probability.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Release probability modulates short-term plasticity at a rat giant terminal.

1. Modulation of release probability is a major factor underlying short-term synaptic plasticity in the central nervous system. We have investigated the relationship between release probability ((Pr) and paired-pulse modulation at a large auditory calyceal synapse containing many transmitter release sites. Whole-cell patch electrode recordings were made of excitatory postsynaptic currents (EPSCs), evoked by stimulation of auditory nerve fibres giving rise to the endbulbs of Held. 2. Quantitative estimates of Pr and quantal amplitude were obtained using the recently developed variance-mean analysis technique. Release probability conditions were modulated by bath application of cadmium, elevated calcium and protein kinase C activation by phorbol esters. 3. Our results show that, under physiological conditions, most sites released neurotransmitter following a single presynaptic nerve impulse, with a mean Pr of 0.6. The mean quantal amplitude was 44 pA, which was consistent with the mean amplitude of miniature EPSCs (47 pA). 4. Under high release probability conditions with elevated calcium or phorbol esters, Pr at all sites approached 1.0. At these high Pr values, variance-mean analysis indicated a significant postsynaptic contribution to paired-pulse depression. The miniature EPSC amplitudes were decreased following stimulation in elevated calcium, confirming a postsynaptic component of paired-pulse depression at this glutamatergic connection. 5. A notable feature was the large variability between neurons in the relationship between paired-pulse ratio and Pr. Based on current models of vesicle release and ultrastructural evidence, we suggest that this variability may be partly due to morphological differences between endbulb specializations, particularly in the ratio of fusion-ready to reserve populations of vesicles at endbulb release sites.

Animals↗
PubMed1999

Glycinergic miniature synaptic currents and receptor cluster sizes differ between spinal cord interneurons.

The structural features of a synaptic connection between central neurons play an important role in determining the strength of the connection. In the present study, we have examined the relationship between the structural and functional properties of glycinergic synapses in the rat spinal cord. We have analyzed the structure of glycinergic receptor clusters on rat ventral horn interneurons using antibodies against the glycine receptor clustering protein, gephyrin. We have examined the properties of quantal glycinergic currents generated at these synapses using whole cell patch-clamp recordings of miniature postsynaptic inhibitory currents (mIPSCs) in rat spinal cord slices in vitro. Our immunolabeling results demonstrate that there is a considerable variability in the size of glycine receptor clusters within individual neurons. Furthermore there are large differences in the mean cluster size between neurons. These observations are paralleled closely by recordings of glycinergic mIPSCs. The mIPSC amplitude varies significantly within and between neurons. Results obtained using combined immunolabeling and electrophysiological recording on the same neurons show that cells with small glycine receptor clusters concurrently exhibit small mIPSCs. Our results suggest that the differences in the size of glycinergic receptor clusters may constitute an important factor contributing to the observed differences in mIPSC amplitude among spinal cord interneurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Cholinergic synaptic transmission in insect mushroom bodies in vitro.

The mushroom body of the bee brain is an important site for learning and memory. Here we investigate synaptic transmission in the mushroom body using extracellular recording techniques in a whole bee brain in vitro preparation. The postsynaptic response showed attenuation by cadmium and paired-pulse facilitation, similar to in vivo findings. This confirms the viability of the in vitro preparation and supports the isolated whole bee brain as a useful model of the in vivo preparation. Bath application of the acetylcholine receptor antagonists, D-tubocurarine and alpha-bungarotoxin attenuated the postsynaptic response by 61 and 62% of control, respectively. The glutamate receptor antagonists, (+)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, had no effect. The invertebrate monoamine and neuromodulator, octopamine, transiently increased the postsynaptic response by 130% of control. These results suggest that synaptic transmission of the olfactory input pathway in the mushroom body is 1) mediated primarily by acetylcholine and 2) modulated by octopamine.

Acetylcholine↗
PubMed1997

Long-term synaptic plasticity in the honeybee.

A monosynaptic response was recorded in vivo in the mushroom body of the bee brain, an important site for memory consolidation. Focal electrical stimulation of a major afferent input evoked an extracellular field potential that consisted of a presynaptic fiber volley and a postsynaptic response. We report a long-lasting potentiation of the synaptic response (2.6-fold increase; < or = 3.5 h). Potentiation of the response was induced by low-frequency stimulation (0.02-1.0 Hz), was input specific, and was maintained in the absence of stimulation. Paired-pulse facilitation of the response was converted to paired-pulse depression after potentiation, suggesting a presynaptic mechanism. This is the first demonstration of long-term synaptic plasticity in the insect brain.

Animals↗
PubMed1995

Cocaine prolongs norepinephrine synaptic potentials in rat dorsal raphe.

1. The effect of cocaine on the excitatory response to norepinephrine (NE) was investigated with the use of intracellular recording from rat dorsal raphe (DR) neurons in the slice preparation. 2. Focal stimulation evoked a slow excitatory postsynaptic potential (sEPSP) that was mediated by alpha 1-adrenoceptor activation. The sEPSP was studied in isolation with the use of a selective 5-HT1A receptor antagonist, pindobind 5HT1A, which eliminated the inhibitory postsynaptic potential (IPSP) that preceded the sEPSP. The sEPSP had a latency to peak of 6 s, a peak amplitude of 6 mV, and a time constant of decay (t) of 14 s. 3. Bath application of cocaine more than doubled the latency-to-peak (13 s) and the time constant of decay (29 s) and had no effect on the amplitude. 4. Iontophoretically applied NE produced a membrane potential depolarization with an amplitude and time course similar to the sEPSP (latency-to-peak = 10 s; peak amplitude = 5 mV; t = 20 s). Cocaine significantly increased the latency-to-peak and the time constant of decay of the depolarization induced by iontophoretically applied NE. 5. Superfusion with NE caused a concentration-dependent depolarization. Cocaine (1 microM) did not change the concentration response to NE. 6. These results suggest that cocaine enhances the excitatory action of NE in the dorsal raphe by a prolongation of the alpha 1-adrenoceptor-mediated sEPSP.

Animals↗
PubMed1995

G alpha o1 decapeptide modulates the hippocampal 5-HT1A potassium current.

1. The serotonin1A (5-HT1A) receptor is coupled to an inwardly rectifying potassium current (IKir) via a G protein. The identity of the G-protein subtype was investigated with 2 10-amino acid peptides derived from the carboxyl (C) terminus of the alpha-subunits of the Go1 and Gi2 proteins (G alpha o1 and G alpha i2). The synthetic decapeptides were applied by intracellular perfusion during whole cell recording from dentate granule cells in the hippocampal slice preparation. 2. Bath application of 5-HT produced an IKir, which was blocked by the selective 5-HT1A receptor antagonist, pindobind5-HT1A. The G alpha o1 peptide inhibited the 5-HT1A IKir by 60 +/- 7% (mean +/- SE; t = 30 min), whereas the G alpha i2 peptide had no effect. The G alpha o1 peptide produced a slowly developing outward current that was not observed in the absence of peptide or in the presence of the G alpha i2 peptide. 3. The results indicate that G alpha o1 and not G alpha i2 modulates the 5-HT1A IKir in hippocampal granule cells. They also suggest that G alpha o1 occludes the 5-HT1A response by direct activation of the IKir. The intracellular perfusion of synthetic G alpha peptides provides a new approach to identify the G-protein subtype(s) in a receptor-mediated electrophysiological response.

Animals↗
PubMed1993

Opioid-glutamate interactions in rat locus coeruleus neurons.

1. The effect of mu-opioids on the glutamate response was investigated in rat locus coeruleus (LC) neurons by intracellular recording in the brain slice preparation. Glutamate responses were evoked by bath application of selective glutamate agonists, glutamate iontophoresis, and stimulation of excitatory afferents. 2. The mu-opioid agonist D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO; 1 microM) potentiated the response to bath application of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid by 91 and 142%, respectively, in slices cut in the horizontal plane. The mechanism of action of this effect was investigated under conditions that limited the DAMGO-induced hyperpolarization and improved the space clamp of the neuron through 1) addition of barium, 2) increase in extracellular potassium concentration, 3) sectioning of the LC in the coronal plane, and 4) addition of carbenoxolone. Each experimental manipulation decreased the DAMGO outward current and reduced the mu-opioid potentiation of the glutamate response. The results suggest that the mu-opioid-mediated potentiation of the glutamate response is dependent on membrane hyperpolarization. 3. Neither forskolin nor the phorbol ester 4b-phorbol 12,13-dibutyrate (PDBu) altered the glutamate-mediated inward currents. The potentiation of the glutamate response by DAMGO was not affected by PDBu. 4. The mu-opioids DAMGO and [met]5enkephalin (10 microM) did not significantly affect the NMDA receptor-mediated depolarization (mean 14%) evoked by local application of glutamate but inhibited the NMDA receptor-mediated synaptic potential (mean 25%).(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Reduction of GABAB inhibitory postsynaptic potentials by serotonin via pre- and postsynaptic mechanisms in CA3 pyramidal cells of rat hippocampus in vitro.

The action of serotonin (5-HT) on GABAergic synaptic transmission was investigated with intracellular recordings in CA3 pyramidal cells of rat hippocampal slices. Local application of 5-HT (500 microM) hyperpolarized CA3 pyramidal cells, decreased cellular input resistance, and reduced slow afterhyperpolarizations. Serotonin attenuated the late (GABAB) component of polysynaptic inhibitory postsynaptic potentials (IPSPs; 47% of control) without affecting the early (GABAA) component. During bath application of the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (20 microM) and 2-amino-5-phosphonovalerate (AP-5) (40 microM), 5-HT similarly decreased the amplitude of the late (GABAB) component (17% of control) of monosynaptic IPSPs but did not affect the early (GABAA) component. The mean reversal potentials of poly- and monosynaptic IPSPs were unaffected by 5-HT. The conductance increases associated with the late component of poly- and monosynaptic IPSPs were reduced by 5-HT. Hyperpolarizing responses evoked in CA3 pyramidal cells by somatic applications of gamma-aminobutyric acid (GABA) were unaffected by 5-HT. During bath application of bicuculline (20-50 microM), hyperpolarizing responses elicited by dendritic GABA application were reduced by 5-HT (71% of control). The effect of 5-HT on these direct GABAB hyperpolarizations (29% decrease in response) does not appear sufficient to fully account for the effect of 5-HT on late GABAB IPSPs (53-83% decrease in response). Therefore, 5-HT may reduce GABAB IPSPs in CA3 pyramidal cells 1) by a postsynaptic action on pyramidal cells and 2) by a selective presynaptic action on GABAergic interneurons mediating the GABAB IPSP. This presynaptic action of 5-HT does not appear to involve excitatory afferents onto inhibitory interneurons.

Animals↗
PubMed1991

Ultrastructural features of the serotonin innervation in adult rat hippocampus: an immunocytochemical description in single and serial thin sections.

This study was aimed at characterizing the fine-structural features of the normal serotonin (5-HT) innervation in adult rat hippocampus, by means of electron microscopic immunocytochemistry with a polyclonal antiserum against 5-HT-glutaraldehyde-protein conjugate (donated by Michel Geffard, Bordeaux). Two hippocampal sectors were examined, at mid-level along the septo-temporal axis: CA3-a of Ammon's horn and crest of the dentate gyrus (DG-c). A large number of axonal varicosities (terminals) were sampled in single ultrathin sections, to achieve a statistically significant comparison of their size and of their relative frequency of synaptic specialization, junctional targets and juxtaposed elements, between the oriens and the radiatum layer of CA3-a, and the molecular and the polymorph layer of DG-c. In both CA3-a layers, the microenvironment of the immunostained terminals was also compared to that of a population of unlabeled varicosities randomly selected from the same micrographs. Moreover, 57 varicosities from the oriens and the radiatum layer of CA3-a were visualized in a long series of thin sections, allowing for their examination from end to end in 43 instances. As measured in single sections, hippocampal 5-HT varicosities were of comparable diameter (0.57 microns on the average) in the two anatomical sectors and four neuropil layers examined. As extrapolated stereologically to whole varicosities, the proportion making a synaptic membrane specialization (synaptic incidence) ranged from 18 to 33% (average of 24%), without statistically significant differences between the two sectors and four layers. The synaptic incidence determined directly from serial sections of CA3-a (18%) was nearly identical to that extrapolated from single sections (18.1% in the oriens and 19.5% in the radiatum layer). In both CA3-a and DG-c, the 5-HT varicosities showing a junctional complex were slightly larger than their non-junctional counterparts. In CA3-a, only dendritic shafts were targeted by synaptic 5-HT varicosities, whereas in DG-c there were also a few axo-spinous synapses. The microenvironment of CA3-a 5-HT varicosities differed markedly from that of randomly selected unlabeled varicosities, due to its much lower frequency of synaptic targets and higher frequency of juxtaposed axonal varicosities, at least in the radiatum layer. In all four layers examined, other axonal varicosities were indeed the most frequently encountered neuronal element in the immediate vicinity of immunostained 5-HT varicosities. Neurites and dendritic shafts were also common, but dendritic spines (4%) were relatively infrequent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Ultrastructural features of serotonin neurons grafted to adult rat hippocampus: an immunocytochemical analysis of their cell bodies and axon terminals.

Serotonin (5-HT) immunocytochemistry was used at the electron microscopic level to examine 5-HT neurons reinnervating and hyperinnervating the hippocampus of adult rat, three to four months after a total 5-HT denervation and subsequent graft of embryonic raphe cells. The study focused on immunostained nerve cell bodies, dendrites and axon terminals (varicosities) in the core of grafts, and on a large single section sampling of axon terminals from a CA3 and a dentate gyrus sector of the outgrowth, which were systematically compared to the endogenous 5-HT innervation of the same regions described in a companion paper. The shape, size and synaptic investment of the grafted 5-HT somata and their dendrites resembled those of in situ 5-HT neurons. Clusters of small, clear vesicles were sometimes seen along these 5-HT dendrites. 5-HT axonal varicosities were fairly numerous in the core. A few were directly apposed to, or made asymmetrical synaptic contact with the immunostained dendrites and perikarya, but the vast majority showed no indication of junctional specialization (synaptic incidence of 19%, as stereologically extrapolated for whole varicosities). Occasional myelinated 5-HT axons were also present in the core of grafts. In the two outgrowth sectors, the graft-borne 5-HT varicosities were similar in size, content, frequency of synaptic contact and identity of junctional and appositional elements, irrespective of their laminar location. Moreover, none of these parameters were significantly different from those of the endogenous innervation. Notably, in spite of their excessive number, the synaptic incidence of the outgrowth 5-HT varicosities remained inferior to 20%. The similarity between the respective microenvironments of the supernumerary, graft-borne 5-HT terminals and of their normal counterparts could only be explained by a random intratissular distribution of these varicosities in both the normal and the grafted hippocampus. Thus, in spite of their transplantation and growth into an abnormal milieu, and the fact that they hyperinnervated the host tissue, the grafted embryonic 5-HT neurons appeared committed to express a particular set of intrinsic and relational morphological features corresponding to their normal adult characteristics.

5,7-Dihydroxytryptamine↗
PubMed1990

Quantified distribution of the serotonin innervation in adult rat hippocampus.

To quantify the serotonin innervation in adult rat hippocampus, serotonin axon terminals (varicosities) were uptake-labeled for light microscope radioautography in whole hemisphere slices incubated with 1 microM [3H]serotonin. The labeled varicosities were visualized as small aggregates of silver grains and counted with the aid of an image analysis system across all layers in representative sectors of subiculum, Ammon's horn (CA1, CA3-a, CA3-b) and dentate gyrus (medial blade, crest and lateral blade). Counts were obtained in six rats at three equidistant horizontal levels from the ventral two-thirds of the hippocampus. After double correction for duration of radioautographic exposure and section thickness, and measurement of the mean diameter of labeled varicosities in electron microscope radioautographs, the results were expressed in number of varicosities per mm3 of tissue. The overall density of hippocampal serotonin innervation was thus evaluated at 2.7 x 10(6) varicosities per mm3, and appeared significantly higher in subiculum (3.6 x 10(6)) and Ammon's horn (3.1 x 10(6)) than in dentate gyrus (2.2 x 10(6)). Subiculum and dentate gyrus-crest (2.0 x 10(6)) had the highest and lowest regional densities. There was a marked heterogeneity also in terms of laminar distribution. For example, the stratum moleculare of subiculum and CA1, and the stratum oriens of CA3 (5.2 x 10(6)) varicosities in CA3-a), showed much higher values than the pyramidal cell layer (0.7, 1.1 and 0.7 x 10(6) in CA1, CA3-a and CA3-b, respectively). Similarly, the granular layer of dentate gyrus had a much lower density (1.1 x 10(6)) than did the molecular (2.8 x 10(6)) and the polymorph layer (2.4 x 10(6)). From these data, it was possible to evaluate the mean endogenous amine content per hippocampal serotonin varicosity (0.05-0.07 fg), and the average number of serotonin varicosities per hippocampal neuron in both CA3 (130) and dentate gyrus (20-35). In the context of current data on the distribution of serotonin receptors and diverse actions of serotonin at the cellular level in hippocampus, such quantified information provides new insights on some basic properties of serotonin in this part of the brain.

Animals↗
PubMed1989

Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat.

A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals (axonal varicosities) in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer (granule) and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus. These figures allow for numerous correlations with other quantitative parameters--cytological, biochemical, and pharmacological--of NA function in the hippocampus. They also provide a strong basis for elucidating, at a cellular level, the action of NA in this part of the brain.

Animals↗
PubMed1988

Quantified regional and laminar distribution of the noradrenaline innervation in the anterior half of the adult rat cerebral cortex.

The regional and laminar distribution of the noradrenaline (NA) innervation in the adult rat cerebral cortex was quantified in radioautographs of semithin sections from whole hemisphere slices incubated with tritiated catecholamines and a monoamine oxidase inhibitor. Uptake-labeled axonal varicosities (aggregates of silver grains) were counted with the help of a computerized image analyzer in seven cytoarchitectonic areas of the rostral half of the cortex: Cg3, rostral AID, Cg2, Fr1, Par1, caudal AID, and Pir (prepiriform) according to Zilles's nomenclature. Both dopamine (DA) and NA terminals were detected after incubation with [3H]DA and citalopram or with [3H]NA alone. In the presence of desipramine (DMI), DA terminals alone were demonstrated; the number of NA terminals was then obtained by subtraction from counts in adjacent slices incubated with or without DMI. These counts suggested that DA and NA varicosities were fully visualized only after labeling with their respective tritiated amine. Similar numbers of labeled NA varicosities as inferred after [3H]NA incubation with or without DMI were observed after [3H]NA incubation in the presence of benztropine (BZ). This indicated that NA terminals were then maximally detected to the exclusion of the DA ones, and the latter approach was adopted for the acquisition of normative data. Since the average diameter of the labeled NA varicosities was known from earlier measurements in electron microscope radioautographs, the initial counts of labeled sites/mm2 of histological section could be expressed as numbers of varicosities/mm3 of tissue following a double correction for incomplete detection at the chosen duration of radioautographic exposure and section thickness. The overall density of NA innervation was thus estimated at 1.2 million varicosities/mm3 of tissue, with no statistically significant differences between the seven cortical areas examined. In every region, the number of NA terminals was the greatest in the molecular layer (1.5-2 times the density in the rest of cortex) and then progressively decreased in the underlying cortex, with a two- to threefold difference between upper and lower layers. These numerical data allowed an estimation to be made of the possible number of cortical NA varicosities per locus coeruleus nerve cell body of origin (at least 300,000), of their average number per cortical neuron (30-50), their actual incidence among all terminals in the cortex (1/1,000), their mean endogenous amine content per varicosity (0.22 fg), and the mean number of recognition sites for the uptake blocker DMI (4,500/varicosity).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗