Biomedical subjects

C Beaulieu

Publications and source records attributed to C Beaulieu.

At least 73 records · Page 4Linked to original sources

PubMed1995

An anatomical substrate for experience-dependent plasticity of the rat barrel field cortex.

The objective of this study was to examine the influence of sensory experience on the synaptic circuitry of the cortex. For this purpose, the quantitative distribution of the overall and of the gamma-aminobutyric acid (GABA) population of synaptic contacts was investigated in each layer of the somatosensory barrel field cortex of rats which were sensory deprived from birth by continuously removing rows of whiskers. Whereas there were no statistically significant changes in the quantitative distribution of the overall synaptic population, the number and proportion of GABA-immunopositive synaptic contacts were profoundly altered in layer IV of the somatosensory cortex of sensory-deprived animals. These changes were attributable to a specific loss of as many as two-thirds of the GABA contacts targeting dendritic spines. Thus, synaptic contacts made by GABA terminals in cortical layer IV and, in particular, those targeting dendritic spines represent a structural substrate of experience-dependent plasticity. Furthermore, since in this model of cortical plasticity the neuronal receptive-field properties are known to be affected, we propose that the inhibitory control of dendritic spines is essential for the elaboration of these functional properties.

Animals↗

PubMed1995

Neonatal sensory deprivation induces selective changes in the quantitative distribution of GABA-immunoreactive neurons in the rat barrel field cortex.

Modified activity of the rat vibrissae from birth to adulthood induces profound alterations of the responsiveness and selectivity of neurons in the contralateral somatosensory barrel field cortex of adult rats. Because these functional properties are under the control of the intracortical inhibitory mechanisms, we investigated the effects of unilateral removal of face pad vibrissae on the quantitative distribution of intracortical gamma-aminobutyric acid (GABA)-immunoreactive neurons in the rat contralateral and ipsilateral barrel field cortices. This distribution was then compared to a population of control animals. For the entire cortical depth, no significant changes in the density (7,700/mm3 vs. 7,400/mm3), proportion (13.6% vs. 14.4%), or size (11.7 microns vs. 12.5 microns) of GABA-immunoreactive neurons were found in the left contralateral vs. the right ipsilateral barrel field cortex. However, in cortical layer IV, contralateral to the deprivation, the density and proportion of GABA-immunoreactive neurons were lower (6,300/mm3 vs. 13,900/mm3, 6.0% vs. 13.6%; P < 0.01), and these neurons were larger (mean projected height of 15.1 microns vs. 10.8 microns; P < 0.01) than in the ipsilateral barrel field cortex, suggesting a specific loss of GABA expression in a subpopulation of small intracortical neurons. In addition to changes in the contralateral layer IV, GABA-immunoreactive neurons located in the ipsilateral granular layer were also affected. Indeed, their numerical density (13,900/mm3) and proportion (13.6%) were higher (P < 0.01) than in both hemispheres of control animals (average of 10,050/mm3 and 9.4%). On the other hand, GABA-immunoreactive neurons in the ipsilateral layer V were less numerous (5,600/mm3, 15.0%) than in both sides of the controls (average of 10,300/mm3, 22.0%; P < 0.01). Thus, our results show that a unilateral sensory deprivation induces highly selective changes in the intracortical GABA inhibitory circuitry of both hemispheres. These changes are located directly at the input of thalamic afferents and at an output layer of corticofugal and commissural axons and could result in a profound reorganization of the excitatory and inhibitory drives of both sides of the sensory-deprived barrel field cortex.

Animals↗

PubMed1995

Postnatal development of GABA neurons in the rat somatosensory barrel cortex: a quantitative study.

As an estimate of the numerical importance of GABA-containing neurons during development, their quantitative distribution was analysed in the primary somatosensory cortex of rats between postnatal days (P) 5 and 60, using the dissector method and GABA postembedding immunocytochemistry. In relation to the overall number of neurons in the barrel field cortex, the proportion of GABA neurons showed an early significant decrease between P5 and P10 from 14 to 11%, most likely due to termination of transient expression of GABA by some cells. It then remained stable until P20, after which it started slowly but steadily to increase, reaching 14% of the total at P60. The absolute number of GABA neurons also increased by nearly 50% during that period, whereas the number of all neurons remained constant. These changes are seemingly due to a subpopulation of neurons, shown to be of small size, which express GABA late in development. Thus, anatomical adjustments of the cortical GABA system may be observed at least until the end of the second postnatal month, reflecting both delayed maturation and adaptation of this inhibitory circuitry. We suggest the existence of three subpopulations of cortical GABA neurons depending on the time of onset and the regulation of their GABA expression: (i) neurons which express GABA before completion of migration and thus provide for its neurotrophic influence, (ii) neurons which express GABA immediately after completion of migration and build up the cortical inhibitory circuitry, and (iii) neurons which express GABA later in development and represent a substrate of experience-dependent plasticity.

Animals↗

PubMed1995

Relational features of acetylcholine, noradrenaline, serotonin and GABA axon terminals in the stratum radiatum of adult rat hippocampus (CA1).

In a well-defined sector of adult rat hippocampus (CA1, stratum radiatum), the ultrastructural features of acetylcholine (ACh), noradrenaline (NA), serotonin (5-HT) and GABA axon terminals (varicosities) were compared by electron microscopy after immunostaining with antibodies against choline acetyltransferase, NA, 5-HT and glutamic acid decarboxylase. Approximately 100 sectional profiles of each type were analyzed for size, presence of a synaptic membrane specialization (synaptic incidence) and composition of the microenvironment. An equivalent number of immunonegative varicosity profiles selected at random from the same micrographs were similarly examined. ACh, NA and 5-HT varicosity profiles were of comparable size, and significantly smaller than GABA profiles. They exhibited a low frequency of junctional specialization, amounting to 7%, 15% and 21%, respectively, when extrapolated to the whole volume of these terminals. In contrast, GABA varicosities appeared entirely synaptic. The ACh, NA and 5-HT varicosities also differed from their GABA counterparts in being juxtaposed to a greater number of unlabeled axonal varicosities and a lower number of dendritic branches. In addition, the microenvironment of immunostained terminals showed a much lower number of dendritic spines than that of immunonegative varicosities. This latter finding was viewed as another indication that predominantly asynaptic varicosities do not maintain particular relationships with their immediate surround. It was also concluded that volume transmission represents a major mode of transmission for ACh, NA and 5-HT in adult rat hippocampus, thus contributing to the properties and functions assigned to these transmitters in this part of brain.

Acetylcholine↗

PubMed1994

Equivalent cell density in three areas of neonatal rat cerebral cortex.

Using the disector method, equivalent cell densities (number of cells per unit volume) were found in the frontal (motor), parietal (somatosensory) and occipital (visual) cortex of neonatal rat (1.2 x 10(6) cells/mm3). As determined with GABA post-embedding immunocytochemistry on semithin sections, at least 11% of these cells expressed GABA. Because neonate frontal cortex is thicker than the parietal or the occipital cortex, the number of cells under an unit area of pial surface was greater in this cortex. This clearly differed from the adult pattern, where the greatest number of cells beneath an unit pial area is that of the somatosensory versus the frontal and the occipital cortex. It suggests that the attainment of the adult number of cells in a cortical column is achieved through differential cell death in the different areas and that the amount of thalamic input could be a crucial determinant of the adult cytoarchitecture.

Animals↗

PubMed1994

Quantitative aspects of the GABA circuitry in the primary visual cortex of the adult rat.

The number and size of synaptic contacts made by GABA-immunoreactive axonal boutons were estimated in each layer of the primary visual cortex (area Oc1M) of adult rats by using the dissector method. Immunoreactivity for GABA was detected with the postembedding immunogold technique on ultrathin sections. Targets of GABA synaptic contacts were also identified to predict the sites of GABA influence in the rat visual cortex. For the total cortical depth, 82 million out of an overall population of 666 million synaptic contacts per mm3 of tissue (or 1 in 8 contacts, 12%) were GABA. Layer IV averaged 62% more GABA contacts per unit volume than did any other cortical layer. Consequently, these represented a larger proportion (1 in 6, 17%) of the overall population of layer IV synaptic contacts. This higher number of GABA contacts was not due to a greater density of GABA boutons, but to an increased number of contacts made by each layer IV GABA bouton (mean of 1.4 contacts per bouton compared to 1.1 in other cortical layers). The total area occupied by the contacts on an average GABA bouton was similar in all layers; the higher number of contacts per GABA bouton in layer IV being compensated for by their smaller size. This observed constancy in the area of synaptic contacts suggests the presence of one or more regulatory mechanisms maintaining optimal numbers of the different macromolecules forming the synaptic contacts. The increased density of GABA contacts in layer IV compared to other cortical layers was due to their greater number targeting distal regions of the dendritic tree. Since layer IV receives the vast majority of thalamocortical terminals and since these axons preferentially target dendritic spines, the specific arrangement of GABA synaptic contacts in this layer could be designed to exert a precise inhibition near the site of the thalamic input and thus serve as the structural basis for the strong GABA-related hyperpolarization that followed the excitatory response after physiological stimulations of the thalamocortical pathway.

Animals↗

PubMed1994

Determinants of anisotropic water diffusion in nerves.

We report NMR diffusion measurements of water in three central nervous system models, namely the nonmyelinated olfactory, and the myelinated trigeminal and optic nerves of the spotted and long-nosed garfish. A similar degree of anisotropy of the average diffusion coefficients (DNMR) is observed for all three freshly excised nerve types (DNMR(parallel)/DNMR-(perpendicular) is 3.6 +/- 1.2, 3.2 +/- 0.9, and 2.6 +/- 0.4 for the olfactory, trigeminal, and optic nerves, respectively). The anisotropy of DNMR for the nonmyelinated olfactory nerve argues strongly that myelin is not a necessary determinant of diffusional anisotropy in ordered axonal systems (even though it may contribute when present). Garfish nerves treated with vinblastine, in order to depolymerize microtubules and inhibit fast axonal transport, also exhibit diffusional anisotropy (DNMR(parallel)/DNMR(perpendicular) is 2.6 +/- 0.4, 2.8 +/- 0.8, and 2.2 +/- 0.7 for the olfactory, trigeminal, and optic nerves, respectively) thus excluding a significant role for microtubules and fast axonal transport in that observed anisotropy.

Animals↗

PubMed1994

Water diffusion in the giant axon of the squid: implications for diffusion-weighted MRI of the nervous system.

To clarify the result that marked diffusional anisotropy had been found in nomyelinated nerve, and in completion of an evaluation of the role of all longitudinal axonal structures, we report NMR measurements of water diffusion in the giant axon of the squid, where diffusional anisotropy is determined by the neurofilamentary structure. The diffusion coefficients of water parallel and perpendicular to the long axis of the squid giant axon at 20 degrees C are (1.61 +/- 0.06) x 10(-5) cm2 s-1 and (1.33 +/- 0.09) x 10(-5) cm2 s-1, respectively, which yield an anisotropic diffusion ratio of 1.2 +/- 0.1. Water diffusion in the squid giant axon is therefore quite rapid and nearly isotropic, thus eliminating the possibility of a significant role for the longitudinally oriented neurofilaments in producing diffusional anisotropy within the axoplasm. In conjunction with our work on garfish nerves therefore, only membranes, either as numerous axonal membranes or as myelin (if present), remain to fulfill the role of the primary determinant of anisotropic water diffusion in nerve and in white matter.

Animals↗

PubMed1994

Membrane properties and synaptic responses of interneurons located near the stratum lacunosum-moleculare/radiatum border of area CA1 in whole-cell recordings from rat hippocampal slices.

1. The membrane properties and synaptic inputs of interneurons, located at the stratum (s.) lacunosum-moleculare and radiatum border (L-M) of the CA1 region, were examined with the use of current-clamp whole-cell recordings in rat hippocampal slices. 2. Biocytin-labeled L-M interneurons had nonpyramidal somata and aspinous, often beaded, dendrites that arborized in s. lacunosum-moleculare and radiatum, sometimes as far as s. moleculare of the dentate gyrus. Their axon coursed and branched in s. lacunosum-moleculare and radiatum. Axon collaterals were also observed traversing the hippocampal fissure and arborizing in s. moleculare of the dentate gyrus and s. radiatum of the CA3 region. 3. Several membrane properties of interneurons were typically nonpyramidal: they had large input resistances, short-duration action potentials followed by prominent fast afterhyperpolarizations, and responded to hyperpolarizing current pulses with little membrane rectification. L-M interneurons showed significant anodal break responses, and their mean membrane time constant was 33 ms. After-depolarizations elicited by subthreshold depolarizing current pulses were larger in amplitude and decayed more slowly at depolarized than hyperpolarized membrane potentials. 4. The majority of L-M interneurons (35 of 49 cells) were silent at resting membrane potentials, whereas other displayed either spontaneous single action potentials (n = 12) or rhythmic bursts (n = 2). The rhythmic bursts were insensitive to the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP-5; 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM), respectively. Both spontaneous single action potentials and burst firing were blocked by membrane hyperpolarization, suggesting that they were intrinsically rather than synaptically generated. 5. L-M interneurons responded with regular sustained firing to depolarizing current pulses at resting membrane potential. However, at more hyperpolarized membrane potentials (near -75 mV), depolarizing current pulses elicited action-potential firing with a delayed onset. This suggests that voltage-sensitive, transient outward currents may be activated in L-M interneurons from hyperpolarized membrane potentials. 6. Electrical stimulation of s. radiatum or lacunosum-moleculare elicited predominantly long-duration excitatory postsynaptic potentials (EPSPs; n = 20 cells), or both EPSPs and inhibitory postsynaptic potentials (IPSPs; n = 17 cells). In most L-M interneurons (35/37), with increasing intensities, up to two action potentials were elicited. Occasionally, larger bursts (3-5 action potentials) were observed (n = 2). 7. The multiphasic components of the synaptic responses became more evident when stimulations were repeated at different membrane potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Numerical data on neocortical neurons in adult rat, with special reference to the GABA population.

The disector method was used to estimate the numerical density of neurons (number per unit volume) and their actual number per column (number under a given area of pial surface), in the occipital (monocular segment of the primary visual area, Oc1M), the parietal (somatosensory barrelfield area, Par1) and the frontal cortex (primary motor area, Fr1) of adult rat. Values were first obtained for all neurons in each layer, and then for GABA neurons as identified with postembedding immunocytochemistry on semithin sections. The numerical density of neurons in the frontal cortex (34,000/mm3) was significantly lower than in the two other neocortical areas (occipital: 52,000; parietal: 48,000/mm3). The GABA population showed a similar difference and consequently represented an equivalent proportion of total (15%) in the three cortical areas. Across layers, there was an alternate distribution of low and high density of neurons from layers II-III to VI in the three cortical areas, with the highest density in layer IV of the two sensory areas. The laminar changes in density of the GABA neurons were not as pronounced as those of the overall population. Consequently, the layers with the highest overall neuronal densities tended to have a lower proportion of GABA neurons and vice versa. There were more neurons under 1 mm2 of surface in the parietal (90,000) than the occipital or the frontal cortex (71,000), which was also true of the GABA neurons. The greater number of neurons per column in the parietal cortex was mostly imputable to layer IV, the main recipient of thalamic axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Histochemical localization of synaptic zinc in the developing cat visual cortex.

The terminal boutons of many neurons in the telencephalon are known to contain a vesicle-bound, chelatable pool of zinc (Zn2+) that can be selectively visualized with histochemical procedures. In this paper, the normal laminar, areal, and ultrastructural distribution of histochemically reactive zinc in the visual cortex of the adult cat as well as its development from birth are described. In the adult cat visual cortex, intense zinc staining was found in layers I, II, III, and V, with layer VI staining only lightly. The primary geniculostriate input zone, layer IV, was conspicuously distinguished by the relative absence of zinc. This distinct pattern was restricted only to areas 17 and 18 and differentiated them from adjacent cortical area 19 laterally and the subadjacent cingulate cortex. The earliest zinc-positive staining in visual cortical areas 17 and 18 was first apparent by postnatal day 2 (P2) and was characterized by staining of a thin layer at the bottom of the cortical plate. By P10, and continuing through P20, synaptic zinc formed a trilaminar pattern of dense staining in areas 17 and 18, which included the top of layer I, and layers III and V. The laminar pattern of synaptic zinc in visual cortex appeared mature by P30, except that the distribution of zinc in layer IV was not uniform. This was most apparent around P50 in tangential sections through layer IV from opened and flattened cortex, where columnar patches of increased zinc staining were apparent in area 17. These columns were approximately 400 microns in diameter, with a centre-to-centre spacing of approximately 900 microns. The distribution of synaptic zinc apparently reflects the process of synaptic maturity of the cat visual cortex and appears to demarcate a particular form of columnar organization in visual cortex.

Animals↗

PubMed1993

Network of GABAergic large basket cells in cat visual cortex (area 18): implication for lateral disinhibition.

Anatomical and immunohistochemical data indicate that, in addition to pyramidal neurons, nonpyramidal cells are exposed to perisomatic inhibition mediated by gamma-aminobutyric acid (GABA)-containing terminals. However, no direct information is available as yet for the origin of GABAergic inputs to morphologically identified GABAergic neurons. In the present paper, we studied the topographical and synaptic relationship between identified GABAergic large basket cells and their immunohistochemically characterized target neurons revealed by parvalbumin-(PV) and GABA immunostaining in the same material. Extracellularly applied biocytin labelled a total of 36 and 9 large basket cells in layers III and V, respectively. Of these, the axonal arborizations of two basket cells, BC1 and BC2, were reconstructed. The axon of BC1 occupied an area of about 2.3 x 2.2 mm2 in layer III, providing a total of 2,755 terminals. The axon of BC2 showed an overall extent of 3.8 x 1.7 mm2 in layer V elongated in the anteroposterior direction, and gave off 1,599 terminals. Immunostaining for PV was carried out to reveal putative nonpyramidal targets for BC1 and BC2. It was found that in addition to immunonegative cells, they established an average of 4-6 perisomatic contacts onto each of 58 (BC1) and 33 (BC2) PV-immunopositive neurons. For electron microscopic verification, 23 terminals apposing the somata of 12 PV-immunopositive neurons were selected. Each terminal was found to establish symmetrical (type II) contacts with its targeted cell. Furthermore, the distribution of soma area of the targeted PV-immunopositive cells and of identified large basket cells showed remarkable similarity, implying that the two populations were actually the same. In addition, the average horizontal distance between neighbouring PV-immunopositive target cells was found to be about 100 microns both in layers III and V. The results suggest that in area 18 the same large basket cell provides direct inhibition to certain pyramidal cells and facilitation to other pyramidal neurons, by inhibiting their presynaptic large basket cells at regular intervals.

Animals↗

PubMed1993

Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo.

Vitamin D is essential for normal insulin secretion in vivo and in vitro. The differential effect of calcium and of the vitamin D endocrine system in the insulin response to secretagogues is still a subject of debate. To study the roles of calcium and the vitamin D system in the in vivo insulin response, GTT and insulin sensitivity tests were conducted in rats presenting vitamin D depletion and hypocalcemia or vitamin D depletion supplemented with calcium alone for 3, 7, or 14 days, vitamin D3 (6.5 nmol/day x 7 days), or 1,25(OH)2D3 (28 pmol/day x 7 days). Serum calcium was 1.28 +/- 0.04 mM in hypocalcemic vitamin D-depleted rats, 1.47 +/- 0.06 (NS), 1.8 +/- 0.2 (P < 0.0002), and 2.04 +/- 0.07 (P < 0.0001) mM after 3, 7, or 14 days, respectively, of calcium supplementation; vitamin D3- or 1,25(OH)2D3-supplemented animals had serum calcium of 2.61 +/- 0.04 or 2.48 +/- 0.05 mM (P < 0.0001 vs. hypocalcemic vitamin D-depleted rats). Rats with hypocalcemia and vitamin D depletion had significantly higher glucose concentrations (P < 0.0005) and lower insulin response during GTT than all other groups (P < 0.001). Differences in insulin sensitivity could not account for differences in response because exogenous insulin administration led to a similar drop in glucose concentrations in all groups, with the nadir averaging 51.7 +/- 2.6% of initial values. To distinguish between calcium and the vitamin D system in the GTT response, rats were treated with a nonhypercalcemic analogue of 1,25(OH)2D3, OCT (28 pmol/day x 4-7 days) with or without dietary calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Production of alginate beads by emulsification/internal gelation. I. Methodology.

Small diameter alginate beads (microspheres) were formed via internal gelation of alginate solution emulsified within vegetable oil. Gelation was initiated by addition of an oil-soluble acid thereby reducing the pH of the alginate solution and releasing soluble Ca2+ from the citrate complex. Smooth, spherical, micron-sized beads were formed. The mean diameter ranged from 200 to 1000 microns, controlled by the reactor impeller design and rotational speed. The technique has potential for large-scale and continuous applications in immobilization.

Alginates↗

PubMed1992

Preferential innervation of immunoreactive choline acetyltransferase synapses on relay cells of the cat's lateral geniculate nucleus: a double-labelling study.

Relationships between cholinergic axons and GABA cells in the lateral geniculate and the perigeniculate nuclei were quantitatively assessed by combining pre-embedding immunocytochemical visualization of choline acetyltransferase with post-embedding immunogold labelling of GABA at the electron microscopic level. In the lateral geniculate nucleus, vesicle-containing profiles immunoreactive for choline acetyltransferase made synapses exclusively with dendritic profiles both within and outside synaptic glomeruli. Only 7.0% (seven of 100 dendrites) of the target dendrites tested were positive for GABA. Of these, the majority (85.7%; 6/7) were dendritic profiles containing synaptic vesicles. This is in contrast with the overall population of geniculate synapses where 21.3% of the targets were GABA-immunopositive, a three-fold significant difference. In the perigeniculate nucleus, immunoreactive choline acetyltransferase synapses targeted mainly dendritic profiles (93.9%; 31/33) and to a lesser extent somata (6.1%). In this nucleus, all unequivocally defined targets were GABA-immunopositive. Cholinergic inputs thus show a preference to target geniculate relay neurons without a strong innervation of GABA-immunoreactive interneurons. In the perigeniculate, however, cholinergic synapses provide a powerful input to GABAergic cells. This suggests that the facilitatory effects of acetylcholine on the excitability of relay cells would be mediated through (i) a direct innervation of the geniculate relay cells, and (ii) a cholinergic inhibitory innervation of the recurrent inhibition to the lateral geniculate nucleus via the perigeniculate nucleus.

Animals↗

PubMed1992

Enrichment of glutamate in zinc-containing terminals of the cat visual cortex.

The presence of glutamate and GABA was examined in zinc-containing terminals of the cat visual cortex using a post-embedding immunogold method. The surface density of immunogold-labelling was also evaluated in morphologically defined ultrastructural elements, namely terminals having round synaptic vesicles and making asymmetrical synapses (RA boutons), terminals with flat vesicles and symmetrical synapses (FS) and glial cell processes. Glutamate immunoreactivity was highest in RA terminals and in zinc-containing boutons. It was lower in FS terminals and lowest in glial cell processes. GABA immunoreactivity was highest in FS terminals and low in all other ultrastructural elements analysed, including zinc-containing terminals. Therefore, zinc-containing terminals show an enrichment of glutamate and they are likely to use this amino acid as their neurotransmitter. Moreover, the fact that many RA terminals that are negative for zinc show an enrichment of immunoreactive glutamate suggests that zinc-containing fibres represent a subpopulation of the glutamate axonal network.

Animals↗

PubMed1992

Calcium calmodulin dependent kinase II in cat visual cortex and its development.

A monoclonal antibody against the alpha-subunit of calcium/calmodulin-dependent protein kinase II (CAM-K II) was used to visualize the kinase in developing kitten visual cortex. CAM-K II was first expressed in neurons of the deep cortical layers (V and VI) at postnatal day 1-4 and appeared in the remaining cortical layers within the first 2 weeks. The level of immunoreactivity declined in cells of layer V and upper layer VI at about 30-40 days of age. By postnatal day 90, the most densely labelled neurons were concentrated in cortical layers II, III, lower layer IV and in layer VI. This laminar pattern remained constant into adulthood. EM studies showed that the kinase was found in both pre- and postsynaptic locations. About twice as many immunopositive neurons were found in cortical layers II-IV and VI in young adult cats when geniculate input was removed by an unilateral thalamic lesion performed early in life. These results indicate that expression of CAM-K II is developmentally regulated in visual cortical neurons; the alteration of immunoreactivity after early LGN lesions suggests that the level of the kinase (or its alpha-subunit) is also regulated by cortical input.

Animals↗

PubMed1991

Enrichment of cholinergic synaptic terminals on GABAergic neurons and coexistence of immunoreactive GABA and choline acetyltransferase in the same synaptic terminals in the striate cortex of the cat.

The synaptic circuits underlying cholinergic activation of the cortex were studied by establishing the quantitative distribution of cholinergic terminals on GABAergic inhibitory interneurons and on non-GABAergic neurons in the striate cortex of the cat. Antibodies to choline acetyltransferase and GABA were used in combined electron microscopic immunocytochemical experiments. Most of the cholinergic boutons formed synapses with dendritic shafts (87.3%), much fewer with dendritic spines (11.5%), and only occasional synapses were made on neuronal somata (1.2%). Overall, 27.5% of the postsynaptic elements, all of them dendritic shafts, were immunoreactive for GABA, thus demonstrating that they originate from inhibitory neurons. This is the highest value for the proportion of GABAergic postsynaptic targets obtained so far for any intra- or subcortical afferents in cortex. There were marked variations in the laminar distribution of targets. Spines received synapses most frequently in layer IV (23%) and least frequently in layers V-VI (3%); most of these spines also received an additional synapse from a choline acetyltransferase-negative bouton. The proportion of GABA-positive postsynaptic elements was highest in layer IV (49%, two-thirds of all postsynaptic dendritic shafts), and lowest in layers V-VI (14%). The supragranular layers showed a distribution similar to that of the average of all layers. The quantitative distribution of targets postsynaptic to choline acetyltransferase-positive terminals is very different from the postsynaptic targets of GABAergic boutons, or from the targets of all boutons in layer IV reported previously. In both cases the proportion of GABA-positive dendrites was only 8-9% of the postsynaptic elements. At least 8% of the total population of choline acetyltransferase-positive boutons, presumably originating from the basal forebrain, were also immunoreactive for GABA. This raises the possibility of cotransmission at a significant proportion of cholinergic synapses in the cortex. The present results demonstrate that cortical GABAergic neurons receive a richer cholinergic synaptic input than non-GABAergic cells. The activation of GABAergic neurons by cholinergic afferents may increase the response specificity of cortical cells during cortical arousal thought to be mediated by the basal forebrain. The laminar differences indicate that in layer IV, at the first stage of the processing of thalamic input, the cholinergic afferents exert substantial inhibitory influence in order to raise the threshold and specificity of cortical neuronal responses. Once the correct level of activity has been set at the level of layer IV, the influence can be mainly facilitatory in the other layers.

Acetylcholine↗